Physiology_Levy

Physiology_Levy. of adrenoreceptors in primary afferent neurons. Phantom limb pain follows traumatic amputation in some individuals. Such phantom pain is clearly not caused by activation of nociceptors in the area in which pain is felt, because these receptors are no longer present.


Physiology_Levy

Physiology_Levy. Lesions of the thalamus or at other levels of the spinothalamocortical pathway may cause central pain, which is a severe spontaneous pain. However, interruption of the nociceptive pathway by the same lesion may simultaneously prevent or reduce the pain evoked by peripheral stimulation. The mechanism of such trauma-induced pain caused by neural damage is poorly understood. The pain appears to depend on changes in the activity and response properties of more distant neurons in the nociceptive system. Transduction in the Somatosensory System


Physiology_Levy

Physiology_Levy. Transduction in the Somatosensory System Unraveling the transduction processes for the somatosensory system has proven difficult because of a variety of factors. The heart of the transduction process occurs at the specialized endings of the peripheral branch of the axon of the sensory neuron (dorsal root ganglia and trigeminal ganglia cells). These endings have channels that are activated by mechanical, thermal, and/or chemical stimuli and that allow the current flow that underlies the local generator potential (see Fig. 5.13 ). The generator potential then triggers spikes in the afferent fiber (see Fig. 5.14 ). However, the fact is that somatosensory axons are found throughout the body at low densities, making purification of the proteins difficult (e.g., compare with the retina, in which photoreceptors are packed at high density onto a small surface).


Physiology_Levy

Physiology_Levy. Complicating matters, the generator potential can be modified by a host of voltage-gated channels, both excitatory (e.g., Na+ and Ca++ channels) and inhibitory (K+ channels). Moreover, as described earlier, in many cases the axon terminal is encapsulated (e.g., Pacinian corpuscles), and the properties of this accessory structure modify the transduction process. They may do so passively, as a result of the mechanical characteristics of the capsule, or actively by having the accessory cells release transmitter in response to a stimulus. An example of the latter is Merkel cells, where recent evidence suggests the Merkel cells and the axon innervating them both have mechanosensitive channels and the Merkel cells release neurotransmitter. Despite these complications, using a number of approaches, our knowledge of somatosensory transduction processes has begun to increase rapidly.


Physiology_Levy

Physiology_Levy. Despite these complications, using a number of approaches, our knowledge of somatosensory transduction processes has begun to increase rapidly. Until recently, ASIC (acid-sensing ion channel) proteins, which belong to the DEG/ENaC family, had been thought to be the channel proteins underlying the cutaneous mechanoactivated currents, because homologs of these proteins underlie the touch sensation in invertebrates such as Caenorhabditis elegans, and because some ASIC proteins are highly expressed in dorsal root ganglion cells. However, the mechanoactivated currents in dorsal root ganglion cells are not affected by knockdown of the ASIC proteins, indicating that they are not the channel underlying cutaneous mechanotransduction. Nevertheless, touch and pain sensitivity is altered in such knockdown mutants, so they may still play a modulatory role in the transduction process.


Physiology_Levy

Physiology_Levy. Currently, Piezo2 is thought to be channel protein underlying the transduction for cutaneous mechanical rapidly adapting responses, because it forms a nonselective cation pore that opens in response to mechanical stimuli. Moreover, the activation and inactivation kinetics of this channel are consistent with its causing the rapidly adapting mechanoactivated current, and it is blocked by agents (gadolinium, ruthenium red) that block these rapidly adapting currents. Furthermore, transfection of ganglion cells with small interfering (si)RNA for Piezo2 blocks the rapid mechanoactivated current in these cells. Lastly, messenger (m)RNA expression of Piezo2 has been shown in dorsal root ganglion cells.


Physiology_Levy

Physiology_Levy. Both low-threshold (light touch) and nociceptive-type ganglion cells have been found to express Piezo2, indicating that it plays a role in both innocuous and painful touch sensation. The Piezo proteins (Piezo1 and Piezo2) are both found in a variety of organs and thus may underlie visceral sensation as well. Piezo2 has been found in the main proprioceptors (muscle spindles and Golgi tendon organs [see ]) and appears to be the main mechanotransducer protein there as well. The receptor that binds capsaicin (the molecule in chili peppers responsible for their spiciness) has been identified, and either it or one of a family of related proteins has been found to be expressed in populations of dorsal root ganglion cells. These proteins belong to the TRP (transient receptor potential) protein family and are currently the most likely candidates for being the transducers of thermal sensations.


Physiology_Levy

Physiology_Levy. It is important to note that many ion channels (and other proteins, e.g., enzymes) are sensitive to temperature; however, in the case of TRP channels, temperature is acting directly as the gating mechanism. The temperatures at which specific TRP channels are active are indicated by arrows in Fig. 7.8 (bottom), in which the direction of each •Fig. 7.8 Temperaturedependenceoffiringratesindifferentthermo-sensitiveafferents.BelowthefiringratecurvesareshowntherangesoverwhichthedifferentTRPchannelsareactivated.Thedirectionofincreasingactivationisindicatedbyanarrowineachcase.Notehowinsomecasestherangeoverwhichanafferentisactive(topgraphs)correspondswelltotheactivationrangeofasingleTRPchannel,thussuggestingthattheafferentwouldneedtoexpressonlyasingletypeofchannel.InothercasestheactiverangeoftheafferentsuggeststhatmultipleTRPchannelswouldbeneededtounderliethecompleteresponsivenessoftheafferent. arrow indicates which temperatures cause greater activation. For comparison,


Physiology_Levy

Physiology_Levy. arrow indicates which temperatures cause greater activation. For comparison, Fig. 7.8 also plots the firing rates of several thermosensitive fibers as a function of temperature. Note how the response ranges of the afferents largely match up with those of individual heat-sensitive channels. The cold fibers, however, show firing over a wider range than any one TRP channel does. One possible explanation for this discrepancy is that dorsal root ganglion cells may express multiple classes of TRP, which would enable them to respond over a wider range of physiological temperatures.


Physiology_Levy


Physiology_Levy

Physiology_Levy. Table7.1 appeartoactastemperaturesensorswithdistinctthermalsensitivitiesthatspantherangeofphysiologicallyrelevanttemperatures. Modulation of the Transduction Process As with the low-threshold mechanoreceptors for innocuous touch sensations, activation of the various nociceptor Thefourthletterinthenameidentifiesthesubfamilyandwaschosenbecauseofthefirstmemberofthesubfamilyidentified:V,vanilloid;M,melastatin;A,ankyrin-like.Eachoftheproteinslistedisexpressedinatleastsomedorsalrootganglioncells,buttheyarealsoexpressedinothercelltypes.


Physiology_Levy

Physiology_Levy. CHAPTER 7 The Somatosensory System transduction proteins leads to a generator potential that causes spiking of the afferent, which transmits information to the CNS. In addition, activation of nociceptors also leads to local release of various chemical compounds, including tachykinins (substance P [SP]) and calcitonin gene–related protein (CGRP). These substances and others released from the damaged cells cause neurogenic inflammation (edema and redness of the surrounding skin).


Physiology_Levy

Physiology_Levy. In addition to causing a local reaction, these substances may serve to activate the insensitive or silent nociceptors mentioned earlier, such that they can henceforth respond to any subsequent damaging stimuli. Sensitization of silent nociceptors has been suggested to underlie allodynia (elicitation of painful sensations by stimuli that were innocuous before an injury) and hyperalgesia (increase in the level of pain felt to already painful stimuli). Thermal hyperalgesia is due to sensitization of TRPV1 channels. The Piezo2 current is increased by substances known to cause mechanical hyperalgesia and allodynia, suggesting changes in this current underlie these phenomena. Centrifugal Control of Somatosensation


Physiology_Levy

Physiology_Levy. Centrifugal Control of Somatosensation Sensory experience is not just the passive detection of environmental events. Instead, it more often depends on exploration of the environment. Tactile cues are sought by moving the hand over a surface. Visual cues result from scanning targets with the eyes. Thus sensory information is often received as a result of activity in the motor system. Furthermore, transmission in pathways to the sensory centers of the brain is regulated by descending control systems. These systems allow the brain to control its input by filtering the incoming sensory messages. Important information can be attended to and unimportant information can be ignored.


Physiology_Levy

Physiology_Levy. The tactile and proprioceptive somatosensory pathways are regulated by descending pathways that originate in the S-I and motor regions of the cerebral cortex. For example, cortical projections to the dorsal column nuclei help control the sensory input that is transmitted by the dorsal column– medial lemniscus pathway.


Physiology_Levy

Physiology_Levy. Of particular interest is the descending control system that regulates transmission of nociceptive information. This system presumably suppresses excessive pain under certain circumstances. For example, it is well known that soldiers on the battlefield, accident victims, and athletes in competition often feel little or no pain at the time a wound occurs or a bone is broken. At a later time, pain may develop and become severe. Although the descending regulatory system that controls pain is part of a more general centrifugal control system that modulates all forms of sensation, the pain control system is so important medically that it is distinguished as a special system called the endogenous analgesia system.


Physiology_Levy

Physiology_Levy. Several centers in the brainstem and pathways descending from these centers contribute to the endogenous analgesia system. For example, stimulation in the midbrain •Fig. 7.9 A,


Physiology_Levy

Physiology_Levy. Opin Neurobiol 2014;29:159.D,RedrawnfromHenryJL.In:PorterR,O’ConnorM[eds]:CibaFoundationSymposium91.London:Pitman;1982.) periaqueductal gray, locus coeruleus, or medullary raphe nuclei inhibits nociceptive neurons at the spinal cord and brainstem level, including spinothalamic and trigeminothalamic tract cells (


Physiology_Levy

Physiology_Levy. Fig. 7.9A-C ). Other inhibitory pathways originate in the sensorimotor cortex, hypothalamus, and reticular formation. The endogenous analgesia system can be subdivided into two components: one component uses endogenous opioid peptides as neurotransmitters and the other does not. Endogenous opioids are neuropeptides that activate one of several types of opiate receptors. Some of the endogenous STT relay cell afferent Circulating opioid binding sites Opiate receptor Sub P. Enk Substance P receptor opioids include enkephalin, dynorphin, and β-endorphin. Opiate analgesia can generally be prevented or reversed by the narcotic antagonist naloxone. Therefore naloxone is frequently used to determine whether analgesia is mediated by an opioid mechanism.


Physiology_Levy

Physiology_Levy. The opioid-mediated endogenous analgesia system can be activated by exogenous administration of morphine or other opiate drugs. Thus one of the oldest medical treatments of pain depends on the triggering of a sensory control system. Opiates typically inhibit neural activity in nociceptive pathways. Two sites of action have been proposed for opiate inhibition, presynaptic and postsynaptic (see Fig. 7.9D ). The presynaptic action of opiates on nociceptive afferent terminals is thought to prevent release of excitatory transmitters such as SP. The postsynaptic action of opiates produces an inhibitory postsynaptic potential. How can an inhibitory neurotransmitter activate descending pathways? One hypothesis is that the descending analgesia system is under tonic inhibitory control by inhibitory interneurons in both the midbrain and medulla. The action of opiates would inhibit the inhibitory inter-neurons and thereby disinhibit the descending analgesia pathways.


Physiology_Levy

Physiology_Levy. Some endogenous analgesia pathways operate by neurotransmitters other than opioids and thus are unaffected by naloxone. One way of engaging a nonopioid analgesia CHAPTER 7 The Somatosensory System pathway is through certain forms of stress. The analgesia thus produced is a form of stress-induced analgesia.


Physiology_Levy

Physiology_Levy. CHAPTER 7 The Somatosensory System pathway is through certain forms of stress. The analgesia thus produced is a form of stress-induced analgesia. Many neurons in the raphe nuclei use serotonin as a neurotransmitter. Serotonin can inhibit nociceptive neurons and presumably plays an important role in the endogenous analgesia system. Other brainstem neurons release catecholamines, such as norepinephrine and epinephrine, in the spinal cord. These catecholamines also inhibit nociceptive neurons; therefore catecholaminergic neurons may contribute to the endogenous analgesia system. Furthermore, these monoamine neurotransmitters interact with endogenous opioids. Undoubtedly, many other substances are involved in the analgesia system. In addition, there is evidence for the existence of endogenous opiate antagonists that can prevent opiate analgesia. 1.


Physiology_Levy

Physiology_Levy. 1. Sensory neurons have cell bodies in sensory nerve ganglia: (1) dorsal root ganglia for neurons innervating the body and (2) cranial nerve ganglia for neurons innervating the face, oral and nasal cavities, and dura, except for proprioceptive neurons, which are in the trigeminal mesencephalic nucleus. They connect peripherally to a sensory receptor and centrally to second-order neurons in the spinal cord or brainstem. 2. Skin contains low-threshold mechanoreceptors, thermoreceptors, and nociceptors. Muscle, joints, and viscera have mechanoreceptors and nociceptors. Low-threshold mechanoreceptors may be rapidly or slowly adapting. Thermoreceptors include cold and warm receptors. Aδ and C nociceptors detect noxious mechanical, thermal, and chemical stimuli and may be sensitized by release of chemical substances from damaged cells. Peripheral release of substances, such as peptides, from nociceptors themselves may contribute to inflammation. 3.


Physiology_Levy

Physiology_Levy. 3. Large primary afferent fibers enter the dorsal funiculus through the medial part of the dorsal root; collaterals synapse in the deep dorsal horn, intermediate zone, and ventral horn. Small primary afferent fibers enter the spinal cord through the lateral part of the dorsal root; collaterals synapse in the dorsal horn. 4. Ascending branches of large primary afferent fibers synapse on second-order neurons in the dorsal column nuclei. These second-order neurons project via the medial lemniscus to the contralateral thalamus and synapse on third-order neurons of the VPL nucleus. The equivalent trigeminal pathway is relayed by the main sensory nucleus to the contralateral VPM nucleus. 5. The dorsal column spinal cord pathways signal the sensations of flutter-vibration, touch-pressure, and proprioception. They also contribute to visceral sensation, including visceral pain. 6.


Physiology_Levy

Physiology_Levy. 5. The dorsal column spinal cord pathways signal the sensations of flutter-vibration, touch-pressure, and proprioception. They also contribute to visceral sensation, including visceral pain. 6. The spinothalamic tract includes nociceptive, thermoreceptive, and tactile neurons; its cells of origin are mostly in the dorsal horn, and the axons cross, ascend in the ventrolateral funiculus, and synapse in the VPL, VPI, and posterior and intralaminar nuclei of the thalamus. The equivalent trigeminal pathway is relayed by the descending trigeminal nucleus and projects to the contralateral VPM and intralaminar nuclei. 7. The spinothalamic relay in the VPL, VPM, and VPI nuclei helps account for the sensory-discriminative aspects of pain. Parallel nociceptive pathways in the ventrolateral funiculus are the spinoreticular and spinomesencephalic tracts; these tracts and the spinothalamic projection to the medial thalamus contribute to the motivational-affective aspects of pain. 8.


Physiology_Levy

Physiology_Levy. 8. Referred pain is explained by convergent input to spinothalamic tract cells from the body wall and from viscera. 9. The VPL and VPM nuclei are somatotopically organized and contain inhibitory circuits. These nuclei contain multiple somatotopic maps, one for each somatosensory submodality. The somatosensory cortex includes the S-I and S-II regions; these regions are also somatotopically organized. 10. The S-I cortex contains columns of neurons with similar receptive fields and response properties. Some S-I neurons are involved in feature extraction. 11. Transmission in somatosensory pathways is regulated by descending control systems. The endogenous analgesia system regulates nociceptive transmission, and it uses transmitters such as endogenous opioid peptides, norepinephrine, and serotonin.


Physiology_Levy

Physiology_Levy. Additional Readings Lau BK, Vaughan CW. Descending modulation of pain: the GABA disinhibition hypothesis of analgesia. Curr Opin Neurobiol. Coste B, Xiao B, Santos JS, et al. Piezo proteins are pore-2014;29:159-164. forming subunits of mechanically activated channels. Nature. Squire L, Berg D, Bloom FE, et al., eds. Fundamental Neuroscience. 4th ed. Waltham, MA: Academic Press; 2013. 2012;483:176-181. Upon completion of this chapter, the student should be able to answer the following questions: 1. What is the dark current, and how does the absorption of a photon change it? 2. What are the synaptic pathways for the central and surround portions of the receptive field of an on-center bipolar cell? Of an off-center bipolar cell? 3. What are the receptive field properties of simple and complex cells in the visual cortex? 4. What is the frequency theory of sound encoding? Why is the place theory also required? 5.


Physiology_Levy

Physiology_Levy. 3. What are the receptive field properties of simple and complex cells in the visual cortex? 4. What is the frequency theory of sound encoding? Why is the place theory also required? 5. What are the stimuli that are normally transduced by the hair cells in the semicircular canals and otolith organs? 6. What are the functional consequences of the differing numbers of different receptor molecules between olfactory and gustatory receptor cells?


Physiology_Levy

Physiology_Levy. 6. What are the functional consequences of the differing numbers of different receptor molecules between olfactory and gustatory receptor cells? he evolution of vertebrates shows a trend called cephalization in which special sensory organs develop in the heads of animals, along with the corresponding development of the brain. These special sensory systems, which include the visual, auditory, vestibular, olfactory, and gustatory systems, detect and analyze light, sound, and chemical signals in the environment, as well as signal the position and movement of the head. The stimuli transduced by these systems are most familiar to humans when they provide conscious awareness of the environment, but they are equally important as the sensory basis for reflexive and subconscious behavior. The Visual System


Physiology_Levy

Physiology_Levy. The Visual System Vision is one of the most important special senses in humans and, along with audition, is the basis for most human communication. The visual system detects electromagnetic waves between 400 and 750 nm long as visible light, which enters the eye and impinges on photoreceptors in a specialized sensory epithelium, the retina. The photoreceptors, rods and cones, can distinguish two aspects of light: its brightness (or luminance) and its wavelength (or color). Rods have high sensitivity for detecting low light intensities but do not provide well-defined visual images, nor do they contribute to color vision. Rods operate best under conditions of reduced lighting (scotopic vision). Cones, in contrast, are not as sensitive to light as rods are and thus operate best under daylight conditions (photopic vision). Cones are responsible for high visual acuity and color vision.


Physiology_Levy

Physiology_Levy. The retina is an outgrowth of the thalamus. Thus information processing within the retina is performed by retinal neurons, and the output signals are carried to the brain by the axons of retinal ganglion cells in the optic nerves. There is a partial crossing of these axons in the optic chiasm that causes all input from one side of the visual space to pass to the opposite side of the brain. Posterior to the optic chiasm, the axons of retinal ganglion cells form the optic tracts and synapse in nuclei of the brain. The main visual pathway in humans targets the lateral geniculate nucleus (LGN) of the thalamus and this nucleus, through the visual radiations, projects the visual information to the visual cortex. Other visual pathways project to the superior colliculus, pretectum, and hypothalamus, structures that participate in orientation of the eyes, control of pupil size, and circadian rhythms, respectively. Structure of the Eye


Physiology_Levy

Physiology_Levy. Structure of the Eye The wall of the eye is composed of three concentric layers ( Fig. 8.1 ). The outer layer, or the fibrous coat, includes the transparent cornea, with its epithelium, and the opaque sclera. The middle layer, or vascular coat, includes the iris and the choroid. The iris contains both radially and circularly oriented smooth muscle fibers, which make up the pupillary dilator and constricter muscles, respectively. The choroid is rich in blood vessels that support the outer layers of the retina, and it also contains pigment. The innermost layer of the eye, the retina, is embryologically derived from the diencephalon and therefore is part of the central nervous system (CNS). The functional part of the retina covers the entire posterior aspect of the eye except for the optic nerve head, or optic disc, which is where the optic nerve axons leave the retina. Because there are no receptors at this location, it is often referred to as the anatomical “blind spot” (see


Physiology_Levy

Fig. 8.1

Physiology_Levy. Fig. 8.1


Physiology_Levy

Physiology_Levy. A number of functions of the eyes are under muscular control. Externally attached extraocular muscles aim the eyes toward an appropriate visual target (see ). These muscles are innervated by the oculomotor nerve •Fig. 8.1 Illustrationofaviewofahorizontalsectionoftherighteye.(RedrawnfromWallGL.The Vertebrate Eye and Its Adaptive Radiation. BloomfieldHills,MI:CranbrookInstituteofScience;1942.)IrisPosterior chamber Anterior chamber Limbus Sclera Choroid Retina Optic disc Fovea Vitreous humor Optic nerve Temporal retina Nasal retina Ciliary body Zonule fibers Nodal point Lens Aqueous humor Cornea (cranial nerve [CN] III), the trochlear nerve (CN IV), and the abducens nerve (CN VI). Several muscles are also found within the eye (intraocular muscles). The muscles in the ciliary body control lens shape and thereby the focus of images on the retina. The pupillary dilator and sphincter muscles in the iris control the amount of light entering the eye, in a way similar to that of the diaphragm


Physiology_Levy

Physiology_Levy. shape and thereby the focus of images on the retina. The pupillary dilator and sphincter muscles in the iris control the amount of light entering the eye, in a way similar to that of the diaphragm of a camera. The dilator is activated by the sympathetic nervous system, whereas the sphincter and ciliary muscles are controlled by the parasympathetic nervous system (through the oculomotor nerve; see


Physiology_Levy

Physiology_Levy. Light enters the eye through the cornea and passes through a series of transparent fluids and structures that are collectively called the dioptric media. These fluids and structures consist of the cornea, aqueous humor, lens, and vitreous humor (see Fig. 8.1 ). The aqueous humor (located in the anterior and posterior chambers) and the vitreous humor (located in the space behind the lens) help maintain the shape of the eye. Although the geometrical optic axis of the human eye passes through the nodal point of the lens and reaches the retina at a point between the fovea and the optic disc (see Fig. 8.1 ), the eyes are oriented by the oculomotor system to a point, called the fixation point, on the visual target. Light from the fixation point passes through the nodal point of the lens and is focused on the fovea. Light from the remainder of the visual target falls on the retina surrounding the fovea.


Physiology_Levy

Physiology_Levy. Normally, light from a visual target is focused sharply on the retina by the cornea and lens, which bend or refract the light. The cornea is the major refractive element of the eye, with a refractive power of 43 diopters (D). However, unlike the cornea, the lens can change shape and vary its refractive power between 13 and 26 D. Thus the lens is responsible for adjusting the optical focus of the eye. Suspensory ligaments (or zonule fibers) attach to the wall of the eye at the ciliary body (see Fig. 8.1 ) and hold the lens in place. When the muscles in the ciliary body are relaxed, the tension exerted by the suspensory ligaments flattens the lens. When the ciliary muscles contract, the tension on the suspensory ligaments is reduced; this process allows the somewhat elastic lens to assume a more spherical shape. The ciliary muscles are activated by the parasympathetic nervous system via the oculomotor nerve.


Physiology_Levy

Physiology_Levy. In this way, the lens allows the eye to focus on, or accommodate to, either near or distant objects. For instance, when light from a distant visual target enters a normal eye (one with a relaxed ciliary muscle), the target image is in focus on the retina. However, if the eye is directed at a nearby visual target, the light is initially focused behind the retina (i.e., the image at the retina is blurred) until accommodation aA diopter is a unit of measurement of optical power that is equal to the reciprocal of the focal length measured in meters. Thus it is a unit of reciprocal length, and a 2-D lens would bring parallel rays of light into focus at a distance of 0.5 m. CHAPTER 8 The Special Senses occurs; that is, until the ciliary muscle contracts, causing the lens to become more spherical, the increased convexity causes the lens to refract the light waves more strongly, bringing the image into focus on the retina.


Physiology_Levy

Physiology_Levy. Proper imaging of light on the retina depends not only on the lens and cornea but also on the iris, which adjusts the amount of light that can enter the eye through the pupil. In this regard, the pupil is analogous to the aperture in a camera, which also controls the depth of field of the image and the amount of spherical aberration produced by the lens. When the pupil is constricted, the depth of field is increased, and the light is directed through the central part of the lens, where spherical aberration is minimal. Pupillary constriction occurs reflexively when the eye accommodates for near vision or adapts to bright light, or both. Thus when a person reads or does other fine visual work, the quality of the image is improved by adequate light. Layers of the Retina The 10 layers of the retina are shown in Fig. 8.2 . The outermost portion is the pigmented epithelium (layer 1), which is just inside the choroid. The pigment cells have


Physiology_Levy

Physiology_Levy. Layers of the Retina The 10 layers of the retina are shown in Fig. 8.2 . The outermost portion is the pigmented epithelium (layer 1), which is just inside the choroid. The pigment cells have Asanindividualages,theelasticityofthelensgraduallydeclines.Asaresult,accommodationofthelensfornearvisionbecomesprogressivelylesseffective,aconditioncalledpresbyopia. Ayoungpersoncanchangethepowerofthelensbyasmuchas14D.However,bythetimethatapersonreaches40yearsofage,theamountofaccommodationhalves,andafter50years,itcandecreaseto2Dorless.Presbyopiacanbecorrectedbyconvexlenses.


Physiology_Levy


Physiology_Levy

Physiology_Levy. •Fig. 8.2 Layers of the Retina. Lightimpingingontheretinawouldbecomingfromthetopofthefigure,andwouldpassthroughallthesuperficiallayerstoreachthephotoreceptorrodsandcones.9 Nerve fiber layer Axons at surface of retina passing via optic nerve, chiasm and tract to lateral geniculate body Ganglion cell Bipolar cell Amacrine cell Horizontal cell Rod Cone Choroid Pigment cells Müller cell (supporting glial cell) 8 Ganglion cell layer 7 Inner plexiform layer 5 Outer plexiform layer 6 Inner nuclear layer 4 Outer nuclear layer 2 Photoreceptor layer 1 Pigment epithelium 3 Outer limiting membrane 10 Inner limiting membrane Inner segment Outer segment tentacle-like processes that extend into the photoreceptor layer (layer 2) and surround the outer segments of the rods and cones. These processes prevent transverse scatter of light between photoreceptors. In addition, they serve a mechanical function in maintaining contact between layers 1 and 2 so that the pigmented epithelium can (1) provide


Physiology_Levy

Physiology_Levy. transverse scatter of light between photoreceptors. In addition, they serve a mechanical function in maintaining contact between layers 1 and 2 so that the pigmented epithelium can (1) provide nutrients and remove waste from the photoreceptors; (2) phagocytose the ends of the outer segments of the rods, which are continuously shed; and (3) reconvert metabolized visual pigment into a form that can be reused after it is transported back to the photoreceptors.


Physiology_Levy

Physiology_Levy. Retinal glial cells, known as Müller cells, play an important role in maintaining the internal geometry of the retina. Müller cells are oriented radially, parallel to the light path through the retina. The outer ends of Müller cells form tight junctions with the inner segments of the photoreceptors, and these numerous connections have the appearance of a continuous layer, the outer limiting membrane (layer 3 of the retina).


Physiology_Levy

Physiology_Levy. Inside the external limiting membrane is the outer nuclear layer (layer 4) that contains the cell bodies and nuclei of the rods and cones. The outer plexiform layer (layer 5) contains synapses between the photoreceptors and retinal interneurons, including bipolar cells and horizontal cells, whose cell bodies are found in the inner nuclear layer (layer 6). This layer also contains the cell bodies of other retinal interneurons (the amacrine and interplexiform cells) and the Müller cells.


Physiology_Levy

Physiology_Levy. The inner plexiform layer (layer 7) contains synapses between the retinal neurons of the inner nuclear layer, including the bipolar and amacrine cells, and the ganglion cells, whose cell bodies lie in the ganglion cell layer (layer 8). As previously mentioned, the ganglion cells are the output cells of the retina; it is their axons that transmit visual information to the brain. These axons form the optic fiber layer (layer 9), pass along the inner surface of the retina while avoiding the fovea, and enter the optic disc, where they leave the eye as the optic nerve. The portions of the ganglion cell axons that are in the optic fiber layer remain unmyelinated, but they become myelinated after they reach the optic disc. The lack of myelin where the Folding of membrane •Fig. 8.3 Rods and Cones. Thedrawingsatthebottom showthegeneralfeaturesofarodandacone.Theinsets showtheoutersegments. axons cross the retina helps permit light to pass through the inner retina with minimal distortion.


Physiology_Levy

Physiology_Levy. axons cross the retina helps permit light to pass through the inner retina with minimal distortion. The innermost layer of the retina is the inner limiting membrane (layer 10) formed by the end-feet of Müller cells. Structure of Photoreceptors: Rods and Cones


Physiology_Levy

Physiology_Levy. Structure of Photoreceptors: Rods and Cones Each rod or cone photoreceptor cell is composed of a cell body (in layer 4), an inner and an outer segment that extend into layer 2, and a set of synaptic terminals that synapse in layer 5 onto other retinal cells (Fig. 8.3 ). The outer segments of cones are not as long as those of rods, and they contain stacks of disc membranes formed by infoldings of the plasma membrane. The outer segments of rods are longer, and they contain stacks of membrane discs that float freely in the outer segment, having completely disconnected from the plasma membrane when formed at the base. Both sets of discs are rich in visual pigment molecules, but rods have a greater visual pigment density, which partly accounts for their greater sensitivity to light. A single photon can elicit a rod response, whereas several hundred photons may be required for a cone response.


Physiology_Levy

Physiology_Levy. The outer segments of the photoreceptors are connected by a modified cilium to the inner segments, which contain a number of organelles, including numerous mitochondria. The inner segments are the sites where the visual pigment is synthesized before it is incorporated into the membranes of the outer segment. In rods, the pigment is inserted into new membranous discs, which are then displaced distally until they are eventually shed at the apex of the outer segment, where they undergo phagocytosis by cells of the pigmented


Physiology_Levy

Physiology_Levy. CHAPTER 8 The Special Senses •Fig. 8.4 Graph of a Plot of the Density of Cones and Rods as a Function of Retinal Eccentricity From the Fovea. Notethatconedensitypeaksatthefovea,roddensitypeaksatabout20degreeseccentricity,andnophotoreceptorsarefoundattheopticdisc,wheretheganglioncellaxonsleavetoformtheopticnerve.(DatafromCornsweetTN.Visual Perception. NewYork:AcademicPress;1970.) epithelium. This process determines the rod-like shape of the outer segments of rods. In cones, the visual pigment is inserted randomly into the membranous folds of the outer segment, and shedding, comparable to that seen in rods, does not take place. Regional Variations in the Retina The macula lutea is the area of central vision and is characterized by a slight thickening and a pale color. The thickness is due to the high concentration of photoreceptors and interneurons, which are needed for high-resolution vision. It is pale because both optic nerve fibers and blood vessels are routed around it.


Physiology_Levy

Physiology_Levy. The fovea, which is a depression in the macula lutea, is the region of the retina with the very highest visual resolution and, as noted previously, the light from the fixation point is focused on the fovea. (A major function of eye movements is to bring objects of interest into view on the fovea.) The retinal layers in the foveal region are unusual because several of them appear to be pushed aside into the surrounding macula. Consequently, light can reach the foveal photoreceptors without having to pass through the inner layers of the retina, and both image distortion and light loss are minimized. The fovea has cones with unusually long and thin outer segments, which allows for high packing density. In fact, cone density is maximal in the fovea, providing for high visual resolution, as well as high quality of the image ( Fig. 8.4


Physiology_Levy

Physiology_Levy. Fig. 8.4 The optic disc, where ganglion cell axons leave the retina, lacks photoreceptors and therefore lacks photosensitivity. Thus it is a so-called blind spot in the visual surface of the retina (see Figs. 8.4 8.9 ). A person is normally unaware of the blind spot because the corresponding part of the visual field can be seen by the contralateral eye and because of the psychological process in which incomplete visual images tend to be completed perceptually.


Physiology_Levy

Physiology_Levy. To be detected by the retina, light energy must be absorbed. This is the job primarily of the rods and cones (a small class of ganglion cells are also photosensitive) and is accomplished by visual pigment molecules located in their outer segments. For both rods and cones, the pigment molecule consists of a chromophore, 11-cis retinal, bound to an opsin protein. The visual pigment found in the outer segments of rods is rhodopsin, or visual purple (so named because it has a purple appearance when light has been absorbed). It absorbs light best at a wavelength of 500 nm. Three variants of visual pigment, resulting from the binding of different opsins to retinal, are found in cones (in most species, each cone expresses one of the three cone pigments). The cone pigments absorb best at 419 nm (blue), at 533 nm (green), and at 564 nm (red). However, the absorption spectrum of these visual pigments is broad so that they overlap considerably ( Fig. 8.5).


Physiology_Levy

Physiology_Levy. Fig. 8.5). •Fig. 8.5 The Spectral Sensitivity of the Three Types of Cone Pigments and of the Rod Pigment (Rhodopsin) in the Human Retina. Notethatthecurvesoverlapandthattheso-calledblueandredconesactuallyabsorbmaximallyinthevioletandyellowranges,respectively.(DatafromSquireLR,etal[eds].Fundamental Neuroscience. SanDiego,CA:AcademicPress;2002.) Despite the differences in spectral sensitivity, the transduction process is similar in rods and cones. The absorption of a photon by a visual pigment molecule leads to the isomerization of 11-cis retinal to all-trans retinal, release of the bond with the opsin, and conversion of retinal to retinol. These changes trigger a second messenger cascade that leads to a change in the electrical activity of the rod or cone (discussed later in this section).


Physiology_Levy

Physiology_Levy. The separation of all-trans retinal from opsin also causes both the loss of its ability to absorb light and bleaching (i.e., the visual pigment loses its color). In both rods and cones, regeneration of the visual pigment molecule is a multistep process: the all-trans retinal is transported to the retinal pigmented cell layer, where it is reduced to retinol, isomerized, and esterified back to 11-cis retinal. It is then transported back to the photoreceptor layer, taken up by outer segments, and recombined with opsin to regenerate the visual pigment molecule, which can again absorb light. There is evidence that cones also use a second pathway to regenerate visual pigment. This pathway is much more rapid and involves transport of the retinal molecule to and from the Müller cells (see Fig. 8.2 ) rather than the pigmented epithelial cells. The potential importance of this more rapid pathway is discussed in the section “


Physiology_Levy

Physiology_Levy. Fig. 8.2 ) rather than the pigmented epithelial cells. The potential importance of this more rapid pathway is discussed in the section “ Ultimately, the transduction process triggered by absorption of photons causes the photoreceptor to hyperpolarize. To understand this action and its consequences fully, it is necessary to know the baseline state of the photoreceptor in the dark (i.e., before it absorbs a photon). In darkness, photoreceptors are slightly depolarized (≈−40 mV) in relation to most neurons because cyclic guanosine monophosphate (cGMP)–gated cation channels in their outer segments are open (Fig. 8.6A ). These channels allow a steady influx of Na+ and Ca2+ . The resulting current is known as the dark current, and the depolarization it causes leads to the tonic release of the neurotransmitter glutamate at the photoreceptor’s synapses.


Physiology_Levy

Physiology_Levy. When light is absorbed in a rod (an equivalent sequence happens in cones), photoisomerization of rhodopsin activates a G protein called transducin (see Fig. 8.6B ). This G protein, in turn, activates cyclic guanosine monophosphate phosphodiesterase, which is associated with the rhodopsin-containing discs, hydrolyzes cGMP to 5′-GMP, and lowers the cGMP concentration in the rod cytoplasm. The reduction in cGMP leads to closing of the cGMP-gated cation channels, hyperpolarization of the rod cell membrane, and a reduction in the release of neurotransmitters. Thus cGMP acts as a “second messenger” to translate the absorption of a photon by rhodopsin into a change in membrane potential.


Physiology_Levy

Physiology_Levy. In sum, in all photoreceptors (cones undergo a process analogous to that described for rod transduction), capture of light energy leads to (1) hyperpolarization of the photoreceptor and (2) a reduction in the release of neurotransmitters. Because of the very short distance between the site of transduction and the synapse, the modulation of neurotransmitter release is accomplished without the generation of an action potential. Adaptation refers to the ability of the retina to adjust its sensitivity according to ambient light. This ability allows the retina to operate efficiently over a wide range of lighting conditions, and it reflects a switching between the use of the cone and rod systems for brightand low-light conditions, respectively.


Physiology_Levy

Physiology_Levy. CHAPTER 8 The Special Senses •Fig. 8.6 A, Drawingofarodwiththeflowofcurrentinthedark.WiththeassistanceoftheNa+,K+pump,therodiskeptdepolarized.B, SequenceofthesecondmessengereventsthatfollowtheabsorptionoflightthroughthereductionofcGMP.BecausecGMPmaintainsopenNa+channelsinthedark,theresultsoflightabsorptionaretheclosingoftheNa+channelsandhyperpolarizationoftherod.cGMP,cyclicguanosinemonophosphate;GC,guanylatecyclase;GTP,guanosinetriphosphate;PDE,phosphodiesterase;Rh,rhodopsin;T,transducin.Passive Na+ influx Na+ current Rh T + + + – PDE GC GMP Light Disc A B cGMP GTP Hyperpolarization Membrane Membrane Na+ Na+ Ca++ K+ Active Na+ efflux


Physiology_Levy


Physiology_Levy

Physiology_Levy. As described previously, absorption of a photon causes 11-cis retinal to be converted to all-trans retinal, which then splits from the opsin (bleaching). The visual pigments in rods and cones are bleached at a similar rate; however, regeneration of the visual pigment occurs much more rapidly in cones than in rods. This difference is, at least in part, due to the cones’ ability to utilize a second pathway for regeneration (see previous section). This more rapid regeneration of visual pigment prevents cones from becoming unresponsive in bright light conditions. In contrast, the slowness of the regeneration of rhodopsin molecules means that at light levels not much above those found in evening hours, essentially all of the rhodopsin molecules are bleached. Thus in bright-light conditions, only the cone system is functioning, and the retina is said to be light-adapted.


Physiology_Levy

Physiology_Levy. When entering a darkened movie theater, a person can observe evidence of the existing light adaptation (decreased light sensitivity in association with the reduced amount of rhodopsin) in the inability to see the empty seats (or much else). The gradual return of the ability to see the seats while the person remains in the theater reflects the slow regeneration of rhodopsin and recovery of function of the rod system, a process known as dark adaptation.


Physiology_Levy

Physiology_Levy. This process refers to the gradual increase in light sensitivity of the retina when in low-light conditions. Rods adapt to darkness slowly as their rhodopsin levels are restored, and, indeed, it may take more than 30 minutes for the retina to become fully dark-adapted. In contrast, cones adapt rapidly to darkness, but their adapted threshold is relatively high, and so they do not function when the ambient light level is low. Thus within 10 minutes in a dark room, rod vision is more sensitive than cone vision and becomes the main system for seeing.


Physiology_Levy

Physiology_Levy. In sum, in the dark-adapted state, primarily rod vision is operative, and thus visual acuity is low and colors are not distinguished (this is called scotopic vision). However, when light levels are higher (e.g., when the movie is projected) and cone function resumes (this is called photopic vision), visual acuity and color vision are restored. There is an intermediate range of light levels at which rod and cones are both functional (mesopic vision). The visual pigments in the cone outer segments contain different opsins. As a result of these differences, the three types of cones absorb light best at different wavelengths. Although the cone pigments have maximum efficiency closer to violet, green, and yellow wavelengths, they are referred to as blue, green, and red pigments, respectively (see Fig. 8.5). The differences in the cone absorption spectra underlie humans’ ability to see colors, as opposed to only shades of gray.


Physiology_Levy

Physiology_Levy. Fig. 8.5). The differences in the cone absorption spectra underlie humans’ ability to see colors, as opposed to only shades of gray. According to the trichromacy theory, the differences in absorption efficiency of the cone visual pigments are presumed to account for color vision because a suitable mixture of three colors can produce any other color. However, a neural mechanism must also exist for the analysis of color brightness because the amount of light absorbed by a visual pigment, as well as the subsequent response of the cell, depends on both the wavelength and the intensity of the light (see


Physiology_Levy

Physiology_Levy. Fig. 8.5 ). Two or three of the cone pigments may absorb a particular wavelength of light, but the amount absorbed by each differs according to its efficiency at that wavelength. If the intensity of the light is increased (or decreased), all will absorb more (or less), but the ratio of absorption among them will remain constant. Consequently, there must be a neural mechanism to compare the absorption of light of different wavelengths by the different types of cones for the visual system to distinguish different colors. At least two different kinds of cones are required for color vision. The presence of three kinds decreases the ambiguity in distinguishing colors when all three absorb light, and it ensures that at least two types of cones will absorb most wavelengths of visible light.


Physiology_Levy

Physiology_Levy. The opponent process theory is based on observations that certain pairs of colors seem to activate opposing neural processes. Green and red are opposed, as are yellow and blue, as well as black and white. For example, if a gray area is surrounded by a green ring, the gray area appears to acquire a reddish color. Furthermore, a greenish red or a bluish yellow color does not exist. These observations are supported by findings that neurons activated by green wavelengths are inhibited by red wavelengths. Similarly, neurons excited by blue wavelengths may be inhibited by yellow wavelengths. Neurons with these characteristics are present both in the retina and at higher levels of the visual pathway and seem to serve to increase the ability to see the contrast between opposing colors. A diagram of the basic circuitry of the retina is shown in


Physiology_Levy

Physiology_Levy. A diagram of the basic circuitry of the retina is shown in Fig. 8.7 . Several features of this circuitry are noteworthy. Input to the retina is provided by light striking the photoreceptors. The output is carried by axons of the retinal ganglion cells to the brain. Information is processed within the retina by the interneurons. The most direct pathway through the retina is from a photoreceptor to a bipolar cell and then to a ganglion cell (see Fig. 8.7). More indirect pathways that provide for intraretinal signal processing involve photoreceptors, bipolar cells, amacrine cells, and ganglion cells, as well as horizontal cells to provide lateral interactions between adjacent pathways.


Physiology_Levy

Physiology_Levy. Rod and cone pathways have several important functional differences in their phototransduction mechanisms and their retinal circuitry. As described previously, rods have more visual pigment and a better signal amplification system than cones do, and there are many more rods than cones. Thus rods function better in dim light (scotopic vision), and loss of rod function results in night blindness. In addition, all rods contain the same visual pigment, so they cannot signal color differences. Furthermore, many rods converge onto individual bipolar cells and the results are very large receptive fields and low spatial resolution. Finally, in bright light, most rhodopsin is bleached, so that rods no longer function under photopic conditions.


Physiology_Levy

Physiology_Levy. Cones have a higher threshold to light and thus are not activated in dim light after dark adaptation. However, they operate very well in daylight. They provide high-resolution vision because only a few cones converge onto individual bipolar cells in cone pathways. Moreover, no convergence occurs in the fovea, where the cones make one-to-one connections to bipolar cells. As a result of the reduced convergence, cone pathways have very small receptive fields and can resolve stimuli that originate from sources very close to each other. Cones also respond to sequential stimuli with good temporal resolution. Finally, cones have three


Physiology_Levy

Physiology_Levy. CHAPTER 8 The Special Senses •Fig. 8.7 Basic Retinal Circuitry. Thearrow attheleftindicatesthedirectionoflightthroughtheretina.Photoreceptors(R)synapseonthedendritesofbipolarcells(B)andhorizontalcells(H)intheouterplexiformlayer.Thehorizontalcellsmakereciprocalsynapticconnectionswithphotoreceptorcellsandareelectricallycoupledtootherhorizontalcells.Bipolarcellsreachsynapseonthedendritesofganglioncells(G)andontheprocessesofamacrinecells(A)intheinnerplexiformlayer.Amacrinecellsconnectwithganglioncellsandotheramacrinecells. different visual pigments and therefore provide for color vision. Loss of cone function results in functional blindness; rod vision is not sufficient for normal visual requirements.


Physiology_Levy

Physiology_Levy. different visual pigments and therefore provide for color vision. Loss of cone function results in functional blindness; rod vision is not sufficient for normal visual requirements. The receptive field of an individual photoreceptor is circular. Light in the receptive field hyperpolarizes the photoreceptor cell and cause it to release less neurotransmitter. The receptive fields of photoreceptors and retinal interneurons determine the receptive fields of the retinal ganglion cells onto which their activity converges. The characteristics of the receptive fields of retinal ganglion cells constitute an important step in visual information processing because all the information about visual events that is conveyed to the brain is contained in ganglion cell activity. The bipolar cell, which receives input from a photoreceptor, can have either of two types of receptive fields, as shown in Fig. 8.8.


Physiology_Levy

Physiology_Levy. The bipolar cell, which receives input from a photoreceptor, can have either of two types of receptive fields, as shown in Fig. 8.8. Both are described as having a center-surround organization in which the light that strikes the central region of the receptive field either excites or inhibits the cell, whereas the light that strikes a region that surrounds the central portion has the converse effect. The receptive field with a centrally located excitatory region surrounded by an inhibitory annulus is called an on-center, off-surround receptive field (see Fig. 8.8A ). Bipolar cells with such a receptive field are described as “on” bipolar cells. The other type of receptive field has an off-center, on-surround arrangement, which characterizes “off” bipolar cells (see Fig. 8.8F


Physiology_Levy

Physiology_Levy. Fig. 8.8F The center response of a bipolar cell receptive field is due to only the photoreceptors that directly synapse with the bipolar cell. Photoreceptor cells respond to light with hyperpolarization and a decrease in glutamate release and respond to the removal of light with depolarization and increased glutamate release. This implies that the difference in the center responses of “on” and “off ” bipolar cells lies in their response to glutamate. In fact, off-center bipolar 136 SECTION2Berne & Levy Physiology A On-center field 0 Sec 0.5 1.0 1.5 Central spot of light Light Peripheral spot F Off-center field B On-center cell responses C Central illumination D Annular illumination E Diffuse illumination 0 Sec 0.5 1.0 1.5 H Central illumination I Annular illumination J Diffuse illumination G Off-center cell responses


Physiology_Levy

Physiology_Levy. Fig. 8.8 Thereceptivefieldsofon-center(A) andoff-center(F) bipolarcellsand,belowthem,thereceptivefieldsofganglioncellsB throughE andG throughJ towhichtheyareconnected.Ganglioncellresponsestocentralspots(upper recording)andperipheralspots(lower recording)areshowninB and G. Alsoshownareresponsestocentral(C andH),surround(D andG),anddiffusewhole-field(E and


Physiology_Levy

Physiology_Levy. J)illuminationintheirreceptivefields.Theganglioncellsandtheon-centerandoff-centerbipolarcellsprovidinginputtotheseganglioncellshavesimilarreceptivefields,butwhereasganglioncellsincreaseordecreasetheirspikefrequency,bipolarcellsdepolarizeorhyperpolarize,withoutgeneratingactionpotentials.(RedrawnfromSquireLRetal[eds].Fundamental Neuroscience. SanDiego,CA:AcademicPress;2002.) cells have ionotropic glutamate receptor channels that open in response to glutamate, and thus they are excited by the removal of light stimuli from the center of their receptive field. In contrast, on-center bipolar cells have metabotropic glutamate receptors that close their channels in response to glutamate. They are depolarized by light on the center of their receptive field, because the reduced release of glutamate by the photoreceptors results in more open metabotropic channels. Thus on-center bipolar cells are excited by light stimulation of the center of their receptive fields.


Physiology_Levy

Physiology_Levy. The antagonistic surround response of bipolar cells is due to photoreceptors that surround those that synapse directly on them. These photoreceptors (which also connect directly with their own bipolar cells) synapse with horizontal cells that participate in complex triadic synapses with many photoreceptors and bipolar cells. The pathway through •Fig. 8.9 Relationshipsamongavisualtarget(long arrow, top),imagesontheretinasofthetwoeyes(middle), andprojectionsoftheganglioncellscarryingvisualinformationabouttheseimages(bottom). Thetargetimageissolargethatitextendsintothemonocularsegmentsoftheeyes,whereonesideofitisseenbyonlytheipsilateraleye.Notehowtheaxonsaresortedinthechiasmsothatallinformationabouttheleftvisualfieldofbotheyesisconveyedtotherightsideofthebrainandallinformationabout therightvisualfieldisconveyedtotheleftside.


Physiology_Levy

Physiology_Levy. continued object movement within the field will not be signaled. P cells respond differently to different wavelengths of light. Because there are blue, green, and red cones, many combinations of color properties are possible, but in fact P cells have been shown to have opposing responses only to red and green or only to blue and yellow (a combination of red and green). These mechanisms can greatly reduce the ambiguity of color detection caused by the overlap in cone color sensitivity and may provide a substrate for the opponency process observations. M cells, on the other hand, respond with phasic bursts of action potentials to the redistribution of light, such as would be caused by the movement of an object within their large receptive fields. M cells are not sensitive to differences in wavelength but are more sensitive to luminance than P cells are.


Physiology_Levy

Physiology_Levy. Thus the output of the retina consists primarily of ganglion cell axons from (1) sustained, linear P cells with small receptive fields that convey information about color, form, and fine details and (2) phasic, nonlinear M cells with larger receptive fields that convey information about illumination and movement. Both exist in on-center and off-center varieties ( Fig. 8.8 The Visual Pathway Retinal ganglion cells transmit information to the brain by way of the optic nerve, optic chiasm, and optic tract. Fig. 8.9 shows the relationships among a visual target, the retinal images of the target in the two eyes, and the projections of retinal ganglion cells to the two hemispheres of the brain. The eyes and the optic nerves, chiasm, and tract are viewed from above. The visual target, an arrow, is in the visual fields of both eyes (see


Physiology_Levy

Physiology_Levy. The visual target, an arrow, is in the visual fields of both eyes (see Fig. 8.9 ) and, in this case, is so long that it extends into the monocular segments of each retina (i.e., one end of the target can be seen by only one eye and the other end by only the other eye). The shaded circle at the center of the target represents the fixation point. The image of the target on the retinas is reversed by the lens system. The left CHAPTER 8 The Special Senses half of the visual target is imaged on the nasal retina of the left eye and the temporal retina of the right eye. Thus the left visual field is seen by the left nasal retina and the right temporal retina. Similarly, the right half of the visual target is imaged on and seen by the left temporal retina and the right nasal retina. The lens system also causes an inversion in the vertical axis, with the upper visual field imaged on the lower retina and vice versa.


Physiology_Levy

Physiology_Levy. The axons of retinal ganglion cells may or may not cross in the optic chiasm, depending on the location of the ganglion cell in the retina (see Fig. 8.9 ). Axons from the temporal portion of each retina pass through the optic nerve, the lateral side of the optic chiasm, and the ipsilateral optic tract and terminate ipsilaterally in the brain. Axons from the nasal portion of each retina pass through the optic nerve, cross to the opposite side in the optic chiasm, and then pass through the contralateral optic tract to end in the contralateral side of the brain. As a result of this arrangement, objects in the left field of vision are represented in the right side of the brain, and those in the right field of vision are represented in the left side of the brain.


Physiology_Levy

Physiology_Levy. Retinal ganglion cell axons can synapse in several parts of the brain, but the main target for vision is the lateral geniculate nucleus (LGN) of the thalamus. There is a point-to-point projection from the retina to the LGN. The LGN thus has a retinotopic map. Cells that represent a particular retinal location are aligned along projection lines that can be drawn across the layers of the LGN. The projection from each eye is distributed to three of the layers of the LGN, one of the magnocellular layers (layers 1 and 2 receive M cell input) and two of the parvocellular layers (layers 3 to 6 receive P cell input). Color-coded ganglion cells project to groups of cells between the major layers, the intralaminar zones. Thus the properties of LGN neurons are very similar to those of retinal ganglion cells. For example, LGN neurons can be classified as P or M cells, and they have on-center or off-center receptive fields.


Physiology_Levy

Physiology_Levy. The LGN also receives input from the visual areas of the cerebral cortex, the thalamic reticular nucleus, and several nuclei of the brainstem reticular formation. The activity of LGN projection neurons is inhibited by interneurons both in the LGN and in the thalamic reticular nucleus. These cells use GABA as their inhibitory neurotransmitter. In addition, the activity of LGN neurons is influenced by corticofugal pathways and by brainstem neurons that transmit signals via monoamine neurotransmitters. These control systems filter visual information and may be important for selective attention. The LGN projects to the primary visual cortex or striate cortex by way of the visual radiations. The visual radiation fibers carrying information derived from the lower half of the appropriate hemiretinas (and therefore the contralateral upper visual field) project to the lingual gyrus, which lies Fig.


Physiology_Levy


Physiology_Levy

Physiology_Levy. on the medial surface of the occipital lobe, just below the calcarine sulcus. Axons in the visual radiation that represent the contralateral lower visual field project to the adjacent cuneus gyrus, which lies just above the calcarine sulcus. Together, the portions of these two gyri that line and border the calcarine sulcus constitute the primary visual cortex (or Brodmann area 17; Fig. 8.10 Like the LGN, the striate cortex contains a retinotopic map. The representation of the macula occupies the most posterior and largest part of both gyri, and progressively more peripheral areas of the retina are projected to more anterior parts of these gyri. Overall, there is an orderly mapping of retinal loci across the surface of the striate cortex (see Fig. 8.10 The geniculostriate pathway ends chiefly in layer 4 of the striate cortex (


Physiology_Levy

Physiology_Levy. Fig. 8.10 The geniculostriate pathway ends chiefly in layer 4 of the striate cortex ( Fig. 8.11 ), whereas the projection from the intralaminar LGN terminates in so-called blobs in layers 2 and 3. Similarly, axons that represent one eye or the other terminate within layer 4C in alternate adjacent patches that define ocular dominance columns. Cortical neurons in such a column respond preferentially to input from one eye. Near the border between two ocular dominance columns, neurons respond about equally to input from the two eyes.


Physiology_Levy

Physiology_Levy. The receptive fields of neurons in the striate cortex, aside from the monocular cells in layer 4C, are more complex than those of LGN neurons. Neurons in other layers may be binocular and respond to stimulation of both eyes, although the input from one eye often dominates (see ). In addition, cortical neurons outside layer 4C often show orientation selectivity (i.e., they respond best when the stimulus, such as a bar or an edge, is oriented and positioned in a particular way;


Physiology_Levy

Physiology_Levy. Fig. 8.12 ). These “simple cells” appear to be responding as though they received input from cells whose concentric center-surround receptive fields were arranged in such a way that their “on” centers were aligned in a row flanked by antagonistic regions. “Complex” cortical •Fig. 8.10 Theleftvisualfieldisrelayed(viatheLGNandvisualradiation)totheprimaryvisualcortexoftherighthemisphere,asapoint-to-pointretinotopicmap.Therepresentationofeachpartofvisualspaceisproportionaltothenumberofafferentaxonswithreceptivefieldsinthatpartofspace.Asaresult,theareaofmacularrepresentation(neartheoccipitalpole)islargerthanthatfortherestofthebinocularandmonocularfields.Notethatthelowerhalfofthefieldisrepresentedinthecuneusgyrusabovethecalcarinesulcusandtheupperhalfofthefieldinthelingualgyrusbelowthesulcus.(RedrawnfromPurvesD,etal[eds].Neuroscience. 3rded.Sunderland,MA:Sinauer;2004.) •Fig. 8.11


Physiology_Levy

Physiology_Levy. 3rded.Sunderland,MA:Sinauer;2004.) •Fig. 8.11 DiagramofvisualinformationflowintothevisualcortexfromtheLGNanditsprojectiontotheextrastriatecortex,tothesuperiorcolliculus(SC),andbacktotheLGN.M,magnocellularpath;P,parvocellularpath.(RedrawnfromSquireLR,etal[eds].Fundamental Neuroscience. SanDiego,CA:AcademicPress;2002.)LGN m cell LGN p cell LGN intralaminar p cell Cortex Cortex SC LGN 4B 2+3 5 6 4C˜4C°Blobs (2+3) neurons are similar to “simple” cells in that they are orientation specific, but instead of having flanking excitatory and inhibitory zones, they respond best to a particular stimulus orientation anywhere in their receptive field. They may also display direction selectivity; that is, they may respond when the stimulus is moved in one direction but not when it is moved in the opposite direction (see


Physiology_Levy

Physiology_Levy. Fig. 8.12 ). The receptive field of a “complex” cell may be thought of as a composite of adjacent “simple” cells with similar orientation selectivity. Because such neurons in a particular zone of the cortex all tend to have the same orientation selectivity, they are considered to form an orientation column (Fig. 8.13 As already discussed, color vision may depend on the presence in the retina of three different types of cones, as well as neurons in the visual pathway that show spectral opposition. Retinal ganglion cells, LGN neurons, and some P cells display spectral opponent properties. The spectral opponent neurons in the striate cortex are found in cortical blobs, and these show double-opponency, in which both the center and the surround portions respond antagonistically


Physiology_Levy

Physiology_Levy. CHAPTER 8 The Special Senses •Fig. 8.12 Simple and Complex Receptive Fields in the Visual Cortex Can Be Generated From Multiple Inputs With Concentric Fields. A andB representon-centerandoff-centerinput,respectively,fromtheretina.Ifthreeon-centercells(A) withadjacentreceptivefieldsconvergedontoonecorticalneuron(E), thatneuron,asimplecell,wouldrespondbesttoalongbarstimulusataspecificlocationandorientation(C). Forthreeoff-centerinputs(B), theresultingreceptivefieldisshowninD. Theconvergenceofmultiplesimplecellsontoanothercorticalneuron(F) wouldresultinacomplexcellthatrespondsbesttoabarstimuluswithaverticalorientationthatcanbeplacedanywherewithinitsreceptivefield.(RedrawnfromSquireLR,etal[eds].Fundamental Neuroscience. SanDiego,CA:AcademicPress;2002.) to two colors. Such a cell, whose center responds to red but not green (R+G−) and whose surround portion responds to green but not red (R−G+), is shown in


Physiology_Levy

Physiology_Levy. Fig. 8.13A . The relationships between the ocular dominance and orientation columns and the cortical color blobs are shown in Fig. 8.13B In animal studies, at least 25 different visual areas have been identified in the cerebral cortex, in addition to the striate cortex (Brodmann area 17, or V1). The extrastriate areas include several parallel pathways of visual processing. The P pathway originates with P cells and functions in the recognition of form and color. Structures in the P pathway include LGN layers 3 to 6, layer 4Cβ of the striate cortex, V4 (Brodmann area 19), and several areas in the inferotemporal region ( Fig. 8.14 ). Processing of form includes recognition of complex visual patterns, such as faces. Color information is processed separately from form. The M pathway originates with M cells and functions in motion detection and control of eye movement. Cortical structures in the M pathway include layers 4B and 4Cα of the striate cortex and areas MT (medial temporal) and


Physiology_Levy

Physiology_Levy. I Cortical blobs, concerned with color Stimulus duration Orientation columns I C C •Fig. 8.13 A, Thereceptivefieldandresponsesofadouble-opponent(R+G−/R−G+)neuroninablobofthestriatecortexasitrespondstovariouscombinationsofredandgreenbars.Thebest“on”responseistoaredbarflankedbytwogreenbars.B, Diagramofthecolumnararrangementofthevisualcortex.OculardominancecolumnsareindicatedbyI(foripsilateral)andC(forcontralateral).Orientationcolumnsareindicatedbythesmallercolumnsmarkedwithshortbarsatvaryingangles.ThecorticalblobscontainneuronslikethatinA andhavespectralopponent-receptivefields. •Fig. 8.14 DistributionofPandMcellinfluencesondifferentareasofthevisualcortex.IT,inferotemporalarea;MST,medialsuperiortemporalarea;MT,medialtemporalarea;V1,striatecortex;V2andV4,higherordervisualareas.MT7 V4 MST Visual cortex Laminae 3-6 Laminae 1,2 Dorsal LGNM-cell pathway P-cell pathway IT V2 V1


Physiology_Levy

Physiology_Levy. MST (medial superior temporal) on the lateral aspect of the temporal lobe, as well as Brodmann area 7a of the parietal lobe (see Fig. 8.14 Both P and M pathways contribute to depth perception or stereopsis, which is dependent on slight differences in the retinal images formed in the two eyes. Stereopsis is useful only for relatively nearby objects. However, in such cases, these disparities provide visual cues about depth. Interestingly, the anatomy of the visual pathways indicates that depth perception must be a cortical function because it depends on convergent input from the two eyes and the left/right eye inputs are parallel but segregated in the LGN and in Layer 4 of striate cortex.


Physiology_Levy

Physiology_Levy. The separation of M and P pathways from the retina through the thalamus and all the cortical regions raises the issue of how all the parts are combined to account for the clear, coherent images of events, objects, and persons that humans perceive. It seems unlikely that all the components that represent a percept, such as parts of a face and whether that face belongs to a familiar person, are somehow converged onto a single neuron that recognizes it. Rather, complex percepts probably arise from the coordinated activity of large sets of neurons across multiple regions of the CNS. The process by which a “binding” of such disparate neuronal elements into a percept is unclear, but one working hypothesis is that it may be accomplished by the temporal synchronization of many anatomically distributed neural events.


Physiology_Levy

Physiology_Levy. Lesionsoftheextrastriatevisualcortexcanproducevariousdeficits.Bilaterallesionsoftheinferotemporalcortexcanresultincorticalcolorblindness(achromatopsia) orinaninabilitytorecognizefaces,evenofclosemembersofthefamily(prosopagnosia). AlesioninareaMTorMSTcaninterferewithmotiondetectionandeyemovements. CHAPTER 8 The Special Senses •Fig. 8.15 Twopuretonesareshownbythesolid anddashed lines. Frequencyisdeterminedfromthewavelengthasindicated.Amplitudeisthepeak-to-peakchangeinsoundpressure.Thetwotoneshavethesamefrequencyandamplitudebutdifferinphase. The superior colliculus of the midbrain is a layered structure that is important for certain types of eye movements (see ). The three most superficial layers are involved exclusively in visual processing, whereas the deeper layers receive multimodal input from the somatosensory and auditory systems, as well as the visual system, particularly from cortical areas involved in eye movement.


Physiology_Levy

Physiology_Levy. Another retinal projection is to the pretectum, which bilaterally activates parasympathetic preganglionic neurons in the Edinger-Westphal nucleus that cause pupillary constriction in the pupillary light reflex. The pretectal areas are also interconnected through the posterior commissure, and thus the reflex causes both ipsilateral (direct) and contra-lateral (consensual) pupillary constriction when a light is shown in one eye. The visual pathways also include connections to nuclei that serve functions other than vision. For example, a retinal projection to the suprachiasmatic nucleus of the hypothalamus controls circadian rhythmicity (see The Auditory and Vestibular Systems


Physiology_Levy

Physiology_Levy. The Auditory and Vestibular Systems The peripheral parts of the auditory and vestibular systems share components of the bony and membranous labyrinths, use hair cells as mechanical transducers, and transmit information to the CNS through the vestibulocochlear nerve (CN VIII). However, the CNS processing and sensory functions of the auditory and vestibular systems are distinct. The function of the auditory system is to transduce sound. This allows us to recognize environmental cues and to communicate with other organisms. The most complex auditory functions are those involved in language. The function of the vestibular system is to provide the CNS with information related to the position and movements of the head in space. Control of eye movement by the vestibular system is discussed in


Physiology_Levy

Physiology_Levy. Sound is produced by compression and decompression waves in air or in other elastic media, such as water. Sound frequency is measured in cycles per second, or hertz (Hz). Each pure tone results from a sinusoidal wave at a particular frequency and is characterized not only by its frequency but also, instantaneously, by its amplitude and phase ( Fig. 8.15 ). Most naturally occurring sound, however, is a mixture of pure tones. Noise is unwanted sound and may have any composition of pure tones. Sound propagates at about 335 m/sec in air. The waves are associated with certain pressure changes, called sound pressure. The unit of sound pressure is Newtons per meter squared (N/m2), but sound pressure is more commonly expressed as the sound pressure level (SPL). The unit of SPL is the decibel (dB):


Physiology_Levy

Physiology_Levy. Equation 8.1 where P is sound pressure and PR is a reference pressure (0.0002 dyne/cm2, the absolute threshold for human hearing at 1000 Hz). A sound with intensity 10 times greater would be 20 dB; one 100 times greater would be 40 dB. The normal young human ear is sensitive to pure tones with frequencies that range between about 20 and 20,000 Hz. The threshold for detection of a pure tone varies with its frequency (


Physiology_Levy

Physiology_Levy. The normal young human ear is sensitive to pure tones with frequencies that range between about 20 and 20,000 Hz. The threshold for detection of a pure tone varies with its frequency ( Fig. 8.16 ). The lowest thresholds for human hearing are, for pure tones, approximately 3000 Hz. The threshold at these frequencies is approximately −3 to −5 dB, in comparison with the reference 0 dB at 1000 Hz. In reference to this scale, normal speech has an intensity of about 65 dB, and its main frequencies fall in the range of 300 to 3500 Hz. Sounds that exceed 100 dB can damage the peripheral auditory apparatus, and those higher than 120 dB can cause pain and permanent damage. As people age, their thresholds at high frequencies rise, thereby reducing their ability to hear such tones, a condition called presbycusis.


Physiology_Levy

Physiology_Levy. • Fig. 8.16 Sound Threshold Intensities at Different Frequencies. The bottom curve indicates the absolute intensity needed to detect a sound. The dashed curve represents the threshold for functional hearing.Thetop curveindicateslevelsatwhichsoundispainfuland damaging. The Ear The peripheral auditory apparatus is the ear, which can be subdivided into the external ear, the middle ear, and the inner ear (Fig. 8.17 The external ear includes the pinna and the external auditory meatus (auditory canal). The auditory canal contains glands that secrete cerumen, a waxy protective substance. The pinna helps direct sounds into the auditory canal and plays a role in sound localization. The auditory canal transmits the sound pressure waves to the tympanic membrane. In humans, the auditory canal has a resonant frequency of about 3500Hz, and this resonance contributes to the low perceptual threshold for sounds in that range.


Physiology_Levy

Physiology_Levy. The external ear is separated from the middle ear by the tympanic membrane (see Fig. 8.17A ). The middle ear contains air. Three ossicles are present and serve to link the tympanic membrane to the oval window of the inner ear. and organ of Corti Scala tympani Scala vestibuli • Fig. 8.17 Ear and Cochlear Structure. A, Location of the right human cochlea in relation to the vestibular apparatus, the middle ear, and the external ear. B,Relationshipsbetweentheouter, middle, and inner ear spaces; the cochlea is depicted unrolled for clarity. CHAPTER 8 The Special Senses 145 • Fig. 8.17, cont’d C, Drawing of a cross-section through the cochlea. The organ of Corti (see Fig. 8.18A and B ) is outlined. Adjacent to the oval window is the round window, another membrane-covered opening between the middle ear and inner ear (see Fig. 8.17A and B


Physiology_Levy

Physiology_Levy. Fig. 8.18A and B ) is outlined. Adjacent to the oval window is the round window, another membrane-covered opening between the middle ear and inner ear (see Fig. 8.17A and B The ossicles include the malleus, the incus, and the stapes. The stapes has a footplate that inserts into the oval window. Behind the oval window is a fluid-filled component of the inner ear, the vestibule. It is continuous with a tubular structure known as the scala vestibuli. Inward movement of the tympanic membrane by a sound pressure wave causes the chain of ossicles to push the footplate of the stapes into the oval window (see Fig. 8.17B ). This movement of the stapes footplate in turn displaces the fluid within the scala vestibuli. The pressure wave that ensues within the fluid is transmitted through the basilar membrane of the cochlea to the scala tympani (described later), and it causes the round window to bulge into the middle ear.


Physiology_Levy

Physiology_Levy. The tympanic membrane and the chain of ossicles serve as an impedance-matching device. The ear must detect sound waves traveling in air, but the neural transduction mechanism depends on movement in the fluid-filled cochlea, where acoustic impedance is much higher than that of air. Therefore, without a special device for impedance matching, most sound reaching the ear would simply be reflected, as are voices from shore when a person is swimming under water. Impedance matching in the ear depends on (1) the ratio of the surface area of the large tympanic membrane advantage of the lever system formed by the ossicles. This impedance matching is sufficient to increase the efficiency of energy transfer by nearly 30 dB in the range of hearing from 300 to 3500 Hz.


Physiology_Levy

Physiology_Levy. The middle ear also serves other functions. Two muscles are found in the middle ear: the tensor tympani attached to the malleus and the stapedius attached to the stapes. When these muscles contract, they damp movements of the ossicles and decrease the sensitivity of the acoustic apparatus. This action can protect the acoustic apparatus against damaging sounds that can be anticipated. However, a sudden explosion can still damage the acoustic apparatus because reflex contraction of the middle ear muscles does not occur quickly enough. The chamber of the middle ear connects to the pharynx through the eustachian tube. Pressure differences between the external ear and middle ear can be equalized through this passage. If fluid collects in the middle ear, as during an infection, the eustachian tube may become blocked. The resulting pressure difference between the external ear and middle ear can produce painful displacement of the tympanic membrane and, in extreme cases, cause rupture of the


Physiology_Levy

Physiology_Levy. ube may become blocked. The resulting pressure difference between the external ear and middle ear can produce painful displacement of the tympanic membrane and, in extreme cases, cause rupture of the tympanic membrane. Unequalized pressure changes as a result of flying or diving can also cause discomfort.


Physiology_Levy

Physiology_Levy. to that of the smaller oval window and (2) the mechanical The inner ear includes the bony and membranous labyrinths. The bony labyrinth is a complex but continuous series of spaces in the temporal bone of the skull, whereas the membranous labyrinth consists of a series of soft tissue spaces and channels lying inside the bony labyrinth. The cochlea and the vestibular apparatus are formed from these structures. The cochlea is a spiral-shaped organ (see Fig. 8.17A ). In humans, the spiral consists of 23 4 turns from a broad base to a narrow apex, although its internal lumen is small at the base and wide at the top. The apex of the cochlea faces laterally (see Fig. 8.17A ). The bony labyrinth component of the cochlea is subdivided into several chambers. The vestibule is the space facing the oval window (see


Physiology_Levy

Physiology_Levy. Fig. 8.17A ). The bony labyrinth component of the cochlea is subdivided into several chambers. The vestibule is the space facing the oval window (see Fig. 8.17A ). Continuous with the vestibule is the scala vestibuli, the spiral-shaped chamber that extends to the apex of the cochlea, where it meets and merges with the scala tympani at the helicotrema. The scala tympani is another spiral-shaped space that winds back down the cochlea and ends at the round window (see Fig. 8.17B ). Separating the two, except at the helicotrema, is the scala media enclosed in the membranous labyrinth. The scala media, or cochlear duct (see Fig. 8.17B and ), is a membrane-bound spiral tube that extends along the cochlea, between the scala vestibuli and scala tympani. One wall of the scala media is formed by the basilar membrane, another by Reissner’s membrane, and the third by the stria vascularis (see Fig. 8.17C


Physiology_Levy

Physiology_Levy. Fig. 8.17C The spaces within the cochlea are filled with fluid. The fluid in the bony labyrinth, including the scala vestibuli and scala tympani, is perilymph, which closely resembles cerebrospinal fluid. The fluid in the membranous labyrinth, including the scala media, is endolymph, which is very different from perilymph. Endolymph, generated by the stria vascularis, contains high [K+] (about 145 mM) and low [Na+] (about 2 mm) and has a high positive potential (about +80 mV) with regard to the perilymph. As a result, a very large potential gradient (about 140 mV) exists across the membranes of the hair cell cilia that extend into the endolymph. (These hair cells, which are the sensory receptors for sound, are discussed in more detail later.) The neural apparatus responsible for transduction of sound is the organ of Corti (see


Physiology_Levy

Physiology_Levy. The neural apparatus responsible for transduction of sound is the organ of Corti (see Fig. 8.17C ), which is located within the cochlear duct. It lies on the basilar membrane and consists of several components, including three rows of outer hair cells, a single row of inner hair cells, a gelatinous tectorial membrane, and a number of types of supporting cells. The organ of Corti in humans contains 15,000 outer and 3500 inner hair cells. The rods of Corti help provide a rigid scaffold. Located on the apical surface of the hair cells are stereocilia, which can be described as nonmotile cilia that contact the tectorial membrane. The organ of Corti is innervated by nerve fibers of the cochlear division of the vestibulocochlear nerve (CN VIII). The 32,000 auditory afferent fibers in humans originate in sensory ganglion cells in the spiral ganglion. These nerve fibers penetrate the organ of Corti and terminate at the bases of the hair cells ( Fig. 8.18


Physiology_Levy

Physiology_Levy. Fig. 8.18 Fig. 8.17C ). Approximately 90% of the fibers end on inner hair cells, and the remainder end on outer hair cells. Thus approximately 10 afferent fibers supply each inner hair cell, whereas other afferent fibers diverge to supply about five outer hair cells each. The inner hair cells clearly provide most of the neural information about acoustic signals that the CNS processes for hearing. The sensory function of the outer hair cells is less clear.


Physiology_Levy

Physiology_Levy. In addition to afferent fibers, the organ of Corti is supplied by efferent fibers, most of which terminate on the outer hair cells. These cochlear efferent fibers originate in the superior olivary nucleus of the brainstem and are often called olivocochlear fibers. The length of the outer hair cells varies; this characteristic suggests that changes in outer hair cell length may affect the sensitivity, or “tuning,” of the inner hair cells. The cochlear efferent fibers may control outer hair cell length. Such a mechanism could conceivably influence the sensitivity of the cochlea and the way that the brain recognizes sound. Other efferent fibers that end on cochlear afferent fibers may be inhibitory, and they may help improve frequency discrimination.


Physiology_Levy

Physiology_Levy. Sound is transduced by the organ of Corti. Sound waves that reach the ear cause the tympanic membrane to oscillate, and these oscillations are transmitted to the scala vestibuli by the ossicles. This creates a pressure difference between the scala vestibuli and the scala tympani (see Fig. 8.17B ) that serves to displace the basilar membrane and, with it, the organ of Corti (see Fig. 8.18A and B ). Because of the shear forces set up by the relative displacement of the basilar and tectorial membranes, the stereocilia of the hair cells bend. Upward displacement bends the stereocilia toward the tallest cilium, which depolarizes the hair cells; downward deflection bends the stereocilia in the opposite direction, which hyperpolarizes the hair cells.


Physiology_Levy

Physiology_Levy. Acommoncauseofdeafnessisthedestructionofhaircellsbyloudsounds.Haircellscanbedestroyed,forexample,byexposuretoindustrialnoiseorbylisteningtoloudmusic.Typically,haircellsincertainpartsofthecochleaareselectivelydamagedbyexposuretohighlevelsofsoundatparticularfrequencies(aspredictedbytheplacetheory),andthushearingmaybelostoveradiscretefrequencyrange.Presbycusis,orthelossofhigh-frequencyhearingwithage,isprobablyincreasedbythelossofhaircellsasaresultoflong-termnoiseexposureinurbanenvironments. In view of the wide range of frequencies and amplitudes of sound stimuli, it is no surprise that hair cell transduction must provide for a fast response. The fast response to deflection of the cilia is based on direct opening of ion channels by so-called tip links that connect the tip of each stereocilium with the shaft of the next taller one (see


Physiology_Levy

Physiology_Levy. CHAPTER 8 The Special Senses •Fig. 8.18 DetailoftheorganofCortiatrest(A) andwithupwardmovementofthebasilarmembrane(B). Theupwardmovementcausesthestereociliatobendbecauseofshearforcesproducedbyrelativedisplacementofthehaircellsandthetectorialmembrane.C, Diagramofahaircellwithtiplinkconnectionsbetweenthehaircellciliatoshowhowshearforcesopenmechanoreceptorchannelsand depolarizethehaircell.


Physiology_Levy

Physiology_Levy. Fig. 8.18C ). With deflection, the tip links are subjected to a lever action that transiently opens the channels, allows the entry of K+ (because of the high [K+] and high potential in endolymph), and depolarizes the hair cell. Several mechanisms have been proposed to account for the equally important rapid adaptation necessary for a high-frequency response. A “spring” response by the tip links would allow the attachment point of the tip link to be moved along the stereocilium’s shaft to reset the mechanical leverage of the tip link. In addition, it has been observed that Ca++ can enter and bind to the open channel, change it to require greater opening force, and thereby reduce the statistical probability of opening.


Physiology_Levy

Physiology_Levy. The potential gradient that induces movement of ions into hair cells includes both the resting potential of the hair cells and the positive potential of the endolymph. As noted previously, the total gradient across the apical membrane of hair cells is about 140 mV. Therefore, a change in K+ conductance in the apical membranes of hair cells results in a rapid current flow that produces the receptor potential in these cells. This current flow can be recorded extracellularly as a cochlear microphonic potential, an oscillatory event that has the same frequency as the acoustic stimulus. The cochlear microphonic potential represents the sum of the receptor potentials of a number of hair cells.


Physiology_Levy

Physiology_Levy. Hair cells, like retinal photoreceptors, release an excitatory neurotransmitter (probably glutamate) when depolarized. The neurotransmitter produces an excitatory postsynaptic potential (EPSP) in the cochlear afferent nerve fibers with which the hair cell synapses. In summary, sound is transduced when oscillatory movements of the basilar membrane cause transient changes in the transmembrane voltage of the hair cells and, finally, the generation of action potentials in cochlear afferent nerve fibers. The activity of a large number of cochlear afferent fibers in the auditory nerve can be recorded extracellularly as a compound action potential. On the basis of differences in width and tension, investigators originally concluded that different parts of the basilar membrane have different resonant frequencies.


Physiology_Levy

Physiology_Levy. On the basis of differences in width and tension, investigators originally concluded that different parts of the basilar membrane have different resonant frequencies. •Fig. 8.19 Different Frequencies of Sound Result in Different Amplitudes of Displacement at Different Sites Along the Organ of Corti. A, Travelingwaveproducedinthebasilarmembranebyasoundof200Hz.Thecurvesata,b,c,anddrepresentdisplacementofthebasilarmembraneatdifferenttimes,andthedashed line istheenvelopeformedbythepeaksofthewaveatdifferenttimes.Maximumdeflectionoccursatabout29mmfromtheovalwindow.B, Envelopesoftravelingwavesproducedbyseveralfrequenciesofsound.Notethatthemaximumdisplacementvarieswithfrequencyandisclosesttothestapeswhenthefrequencyishighest.(RedrawnfromvonBekesyG.Experiments in Hearing. NewYork:McGraw-Hill;1960.)


Physiology_Levy

Physiology_Levy. For example, the basilar membrane is about 100 µm wide at the base and 500 µm wide at the apex. It also has higher tension at the base. Thus, the investigators predicted that the base would vibrate at higher frequencies than would the apex, as do the shorter strings of musical instruments. Experiments have shown that the basilar membrane moves as a whole in traveling waves ( Fig. 8.19 ), but displacement of the basilar membrane is maximal nearer the base of the cochlea during high-frequency tones and maximal nearer the apex during low-frequency tones.


Physiology_Levy

Physiology_Levy. Fig. 8.19 ), but displacement of the basilar membrane is maximal nearer the base of the cochlea during high-frequency tones and maximal nearer the apex during low-frequency tones. In effect, the basilar membrane serves as a frequency analyzer; it distributes the stimulus along the organ of Corti, and different hair cells respond differentially to particular 50 Hz frequencies of sound. This is the basis of the place theory of hearing. In addition, hair cells located at different places along the organ of Corti may be tuned to different frequencies because of variations in their stereocilia and biophysical properties. As a result of these factors, the basilar mem brane and organ of Corti have a so-called tonotopic map ( Fig. 8.20).


Physiology_Levy

Physiology_Levy. Fig. 8.20). Neurotransmitter release by hair cells in the organ of Corti can evoke action potentials in the primary afferent fibers of the cochlear nerve. Afferent fibers in the vestibulocochlear nerve (CN VIII) are bipolar cells with a myelin sheath around the cell bodies, as well as around the axons. The cell bodies are in the spiral ganglion, their peripheral processes synapse at the base of hair cells, and their central processes 400 Hz synapse in the cochlear nuclei of the brainstem. acteristic frequency. The characteristic frequency can be determined from a tuning curve for the fiber (


Physiology_Levy

Physiology_Levy. acteristic frequency. The characteristic frequency can be determined from a tuning curve for the fiber ( Fig. 8.21 ). A tuning curve is a plot of the threshold for activation of the nerve fiber by different sound frequencies. The major factor that influences the activity of individual afferent fibers is the location along the basilar membrane of the hair cells that they innervate. The location of those hair cells is important because for any given sound frequency, there is Distance from stapes (mm) a site of maximum displacement of the basilar membrane B as the pressure wave travels along its length (see Fig. 8.19 ). Typically, tuning curves are sharp near the characteristic CHAPTER 8 The Special Senses


Physiology_Levy

Physiology_Levy. Fig. 8.19 ). Typically, tuning curves are sharp near the characteristic CHAPTER 8 The Special Senses Base20,0007,0005,0001,0004,0003,0006004002002,0001,500800Apex •Fig. 8.20 Thetonotopicmapofthecochlea.(RedrawnfromStuhlmanO.An Introduction to Biophysics. NewYork:JohnWiley&Sons;1943.) frequency, but they broaden at high sound pressure levels. Tuning curves can have excitatory and inhibitory areas (see Fig. 8.21A ). The sharpness of the excitatory regions may reflect inhibitory processes. The different features of an acoustic stimulus are encoded in the discharges of cochlear nerve fibers. Duration is signaled by the duration of activity; intensity is signaled both by the amount of neural activity and by the number of fibers that discharge. For low-frequency sounds, the frequency is signaled by the tendency of an afferent fiber to discharge in phase with the stimulus (phase locking; see


Physiology_Levy

Physiology_Levy. Fig. 8.22A ). If the tone is much more than 1 kHz, a single fiber cannot discharge with every cycle, but phase locking can also occur for sounds with periods shorter than the absolute refractory period of the afferent fiber. This allows the CNS to detect higher frequency information from the activity of a population of afferent fibers, each of which discharges in phase with the stimulus and which, as a group, signal the frequency of the stimulus (see Fig. 8.22B ). This observation is the basis of the frequency theory of hearing. For still higher frequencies (>5000 Hz), the place theory dominates: the CNS interprets sounds that activate afferent fibers supplying hair cells near the base of the cochlea as being of high frequency. Thus both the place and the frequency theories are necessary to explain the frequency coding of sound (duplex theory) across the entire range from 20 to 20,000 Hz.


Physiology_Levy

Physiology_Levy. 2 A 7 10 154 –80 –60 –40 –20 0 Frequency (kHz) E I I Threshold intensity (dB) B 0.2 1 2052 100.5 Frequency (kHz) –100 –80 –60 –40 –20 0 Threshold intensity (dB) •Fig. 8.21 Tuning Curves of Neurons in the Auditory System. Tuningcurvescanbeconsideredasreceptivefieldplots.A, Tuningcurvewithcentralexcitatoryfrequencies(E)andflankinginhibitoryfrequencies(I).B, Tuningcurvesforcochlearnervefibers.(A, RedrawnfromArthurRM,etal.J Physiol [Lond] 1971;212:593.B, RedrawnfromKatsuiY.In:RosenblithWA[ed].Sensory Communication. Cambridge,MA:MITPress;1961.)


Physiology_Levy


Physiology_Levy

Physiology_Levy. Cochlear afferent fibers synapse on neurons of the dorsal and ventral cochlear nuclei. The neurons in these nuclei have axons that contribute to the central auditory pathways. Some of the axons from the cochlear nuclei cross to the contralateral side and ascend in the lateral lemniscus, the main ascending auditory tract. Others connect with various ipsilateral or contralateral nuclei, such as the superior olivary nuclei, which project through the ipsilateral and contralateral lateral lemnisci. Each lateral lemniscus ends in an inferior colliculus. Neurons of the inferior colliculus project to the medial geniculate nucleus of the thalamus, which gives rise to the auditory radiation. The auditory radiation ends in the primary auditory cortex (Brodmann areas 41 and 42), located on the superior surface of the temporal lobe.


Physiology_Levy

Physiology_Levy. The input from each ear is bilaterally represented in the ascending auditory system pathway at the level of the lateral lemniscus and above. Thus the representation of auditory space is complex, even at the brainstem level. Consequently, unilateral deafness may occur with isolated lesions of the cochlear nuclei or more peripheral structures. Central lesions do not cause unilateral deafness, although they may interfere with overall sensitivity to speech or with sound localization. Functional Organization of the Central Auditory System The responses of neurons in several structures that belong to the auditory system can be described by tuning curves (see


Physiology_Levy

Physiology_Levy. Functional Organization of the Central Auditory System The responses of neurons in several structures that belong to the auditory system can be described by tuning curves (see Fig. 8.21B ). By plotting the distribution of the characteristic frequencies of neurons within a nucleus or in the auditory cortex, a tonotopic map may be revealed in which neurons are ordered according to their “best” frequencies. Tonotopic maps have been found in the cochlear nuclei, superior olivary complex, inferior colliculus, medial geniculate nucleus, and auditory cortex. A given auditory structure may, in fact, contain several tonotopic maps.


Physiology_Levy

Physiology_Levy. Most auditory neurons at levels above the cochlear nuclei respond to stimulation of either ear (i.e., they have binaural receptive fields). Binaural receptive fields contribute to sound localization. A human can distinguish sounds originating from sources separated by as little as 1 degree. The auditory system uses several clues to judge the origin of sounds, including differences in the time (or phase) of arrival of the sound at the two ears and differences in sound intensity on the two sides of the head.


Physiology_Levy

Physiology_Levy. For example, neurons in the medial superior olivary nucleus have medial and lateral dendrites. The synapses on the medial dendrites are largely excitatory, and they originate from the contralateral ventral cochlear nucleus. Those on the lateral dendrites are mostly inhibitory and come from the ipsilateral ventral cochlear nucleus. Differences in the phase of the sound reaching the two ears affect the strength and timing of the excitation and inhibition reaching a particular medial superior olivary neuron. The lateral superior olivary nucleus processes differences in the sound intensity that reaches the two ears to provide information about the source of the sound. The activity of superior olivary neurons can provide information about sound localization.


Physiology_Levy

Physiology_Levy. Several features of the primary auditory cortex resemble those of other primary sensory areas. Not only are sensory maps—in this case, tonotopic maps—present in the auditory cortex but also this cortical region performs feature extraction. Neurons in the primary auditory cortex form isofrequency columns (in which the neurons in the column have the same characteristic frequency), and they also form alternating columns, known as summation and suppression columns. Neurons in summation columns are more responsive to binaural than to monaural input. Neurons in suppression columns are less responsive to binaural than to monaural stimulation, and, accordingly, the response to one ear is dominant. Some neurons are selective for the direction of frequency change.