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Anatomy_Gray. Tectospinal tract axons arise from cell bodies located in the superior colliculus of the dorsal midbrain (eFig. 9.56). These axons decussate in the dorsal tegmental decussation shortly after leaving the nucleus to form the tectospinal tract along the midline of the brainstem. The tectospinal tract continues through the brainstem near the medial longitudinal fasciculus and into cervical regions of the spinal cord near the anterior median fissure. Within the cervical spinal cord, axons project bilaterally to synapse on cell bodies of interneurons in the anterior horn gray matter. As the superior colliculus receives visual input, it is believed that the tectospinal tract modulates reflex postural movements in response to visual stimuli.


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Anatomy_Gray. Vestibulospinal tract axons arise from vestibular nuclei located in the pons and medulla. The medial vestibular nucleus gives rise to the medial vestibulospinal tract, which projects bilaterally to thoracic regions of the spinal cord, and the lateral vestibular nucleus gives rise to the lateral vestibulospinal tract, which descends ipsilaterally through the entire length of the spinal cord to synapse on interneurons in the anterior horn gray matter (eFig. 9.57). Given that the vestibular nuclei receive sensory input from the inner ear and cerebellum, this tract facilitates activity of extensor/antigravity muscles and inhibits activity of flexor muscles to maintain balance and an upright posture. As an example, the change in head position induced during tripping initiates extension of the upper limb and/or lower limb to prevent oneself from falling forward.


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Anatomy_Gray. Reticulospinal tract axons arise from the reticular formation in the pons and medulla. The axons of the pontine and medullary reticulospinal tracts descend ipsilaterally through the length of the spinal cord in the anterior white matter and synapse with interneurons in the anterior horn gray matter. They are believed to function in regulating voluntary movements in reflex activity and autonomic outflow (eTables 9.5 and 9.6).


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Anatomy_Gray. Vascular perfusions to the spinal cord are supplied by three longitudinally running vessels and several segmental branches. The longitudinally running vessels are the anterior spinal artery and two posterior spinal arteries. The posterior spinal arteries originate in the cranial cavity as branches of either the vertebral artery or PICA. These arteries descend along the length of the posterior spinal cord on the posterolateral sulcus. The single anterior spinal artery originates within the cranial cavity from the union of two contributing branches from the vertebral arteries. The anterior spinal artery descends along the length of the anterior spinal cord on the anterior median fissure.


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Anatomy_Gray. Reinforcing vascular supply to these longitudinally running vessels is provided by eight to ten segmental medullary arteries. The largest segmental medullary artery is the artery of Adamkiewicz in the lower thoracic or upper lumbar region. This vessel is typically on the left side and contributes significantly to perfusion of the lower portion of the spinal cord. Venous drainage of the spinal cord occurs through a series of longitudinally running channels that connect with the anterior and posterior spinal veins on the surface of the cord. Part VI: Basal nuclei


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Anatomy_Gray. Part VI: Basal nuclei The basal nuclei are a collection of gray-matter structures named for their location deep within the base of the forebrain. Functionally, the basal nuclei have a significant role in controlling posture and voluntary movement through connections to the thalamus, cortex, and neighboring basal nuclei structures. In addition to their role in posture and movement, the basal nuclei have connections to limbic system pathways, which govern the expression of various behaviors and motivational states. For the purposes of this section, we will focus on reviewing the structures of the basal nuclei and pathways involved in controlling posture and voluntary movement.


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Anatomy_Gray. A variety of terminology is used to refer to the structures of the basal nuclei individually and based on their collective morphology. To appreciate the three-dimensional shape of the basal nuclei and their relationship to surrounding structures, it is best to view them in horizontal and coronal brain sections taken at different levels of the brain. The corpus striatum (Latin for “striped body”) includes the caudate nucleus and lentiform nucleus. This collection of structures received their name because of the striated appearance of bands that interconnect the caudate nucleus and putamen of the lentiform nucleus through the anterior limb of the internal capsule (eFig. 9.58).


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Anatomy_Gray. The lentiform nucleus (Latin for “lens-shaped”) includes the globus pallidus and putamen, which appear lens-shaped when viewed laterally. Both of these structures are lateral to the internal capsule, which separates them from the thalamus and caudate nucleus medially (eFig. 9.58). Laterally, the putamen is bordered by the external capsule, a thin layer of white matter adjacent to a thin gray-matter layer called the claustrum. Beyond the claustrum is the external capsule, which borders the white matter of the insula (eFig. 9.58).


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Anatomy_Gray. Medial to the internal capsule is the caudate nucleus. The caudate nucleus is a large C-shaped structure divided into a head, body, and tail, which closely follows the shape of the lateral ventricle (eFig. 9.58). Rostrally, the head of the caudate has a large rounded shape that contributes to the lateral wall of the anterior horn of the lateral ventricle (eFig. 9.58). Also at this level, the head of the caudate is continuous with the putamen (eFig. 9.59). Because of this close relationship the putamen and caudate are referred to collectively as the striatum. At the level of the interventricular foramen, the head of the caudate transitions to the body. The body of the caudate is long and narrows substantially as it transitions from the head to the tail (eFig. 9.59). Along its course the body contributes to the floor of the lateral ventricle. Near the posterior border of the thalamus the body of the caudate transitions into the tail. The tail continues anteriorly within the roof of the


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Anatomy_Gray. contributes to the floor of the lateral ventricle. Near the posterior border of the thalamus the body of the caudate transitions into the tail. The tail continues anteriorly within the roof of the inferior horn of the lateral ventricle to terminate in the amygdaloid nucleus (eFig. 9.59).


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Anatomy_Gray. Input to the basal nuclei is primarily received by the striatum (caudate nucleus and putamen), and output predominantly leaves from the globus pallidus. Many structures send input to the striatum, including all areas of the cerebral cortex, thalamic nuclei, subthalamic nucleus, brainstem, and substantia nigra. To understand how the basal nuclei integrates all of this incoming information to influence motor activity, two simplified neuronal loops are described: the direct pathway and the indirect pathway.


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Anatomy_Gray. The direct pathway has a series of connections through the basal nuclei, which result in an overall increase in motor activity. This pathway begins with input to the striatum, which sends axonal connections to the globus pallidus (eFig. 9.60A). The globus pallidus then has output connections to the thalamus, which completes the circuit with axonal connections back to the cortex. The indirect pathway has a similar course, with the addition of output connections to the subthalamic nucleus, which results in an overall decrease in motor activity (eFig. 9.60B). Part VII: Cerebellum


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Anatomy_Gray. Part VII: Cerebellum The cerebellum is the largest structure of the hindbrain. It resides within the posterior cranial fossa and is composed of two large hemispheres, which are connected by the vermis in the midline (eFig. 9.61). Functionally, the cerebellum plays a role in maintaining balance and influencing posture and is responsible for coordinating movements by synchronizing contraction and relaxation of voluntary muscles. We will first examine the structural organization of the cerebellum and then review how these structures contribute to the circuitry of the cerebellum.


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Anatomy_Gray. Within the posterior cranial fossa, the cerebellum is covered by the tentorium cerebelli of the dura mater (eFig. 9.17) and connects to the posterior surface of the brainstem via the superior, middle, and inferior cerebellar peduncles (eFig. 9.62). Anteriorly, the cerebellum forms the roof of the fourth ventricle (eFig. 9.14). On its surface, the cerebellum has several convoluted folds, or folia, separated by fissures. Two of these fissures serve as landmarks to divide the cerebellum into three lobes. Superiorly, the primary fissure separates the anterior lobe from the posterior lobe (eFig. 9.61). Anteriorly and inferiorly, the posterolateral fissure defines the structures of the flocculonodular lobe, which includes the flocculus from each hemisphere and nodule of the vermis (eFig. 9.63). A third fissure, the horizontal fissure, borders the superior and inferior surfaces of the cerebellum (eFig. 9.64).


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Anatomy_Gray. Each fold or folia of the cerebellar cortex has a central core of white matter covered by a thin layer of gray matter superficially. In sections parallel to the median plane, the branching pattern of the folia can be appreciated; this is often referred to as the arbor vitae (eFig. 9.28). Deep within the white matter of each hemisphere are four masses of cerebellar nuclei. From lateral to medial they are the dentate, emboliform, globose, and fastigial (eFig. 9.65). Note that the emboliform and globose are collectively referred to as the interposed nuclei. Output from the cerebellum originates from one of these four nuclear complexes before leaving through the superior cerebellar peduncle, predominantly. In general, the output from each cerebellar hemisphere coordinates movement on the ipsilateral side of the body.


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Anatomy_Gray. Functionally, the cerebellar cortex can be divided into three areas. The vermis in the midline influences movements along the axis of the body, including the neck, trunk, abdomen, and pelvis (eFig. 9.66). Adjacent to the vermis, the intermediate zone controls muscles of the distal upper and lower limbs. The lateral zone participates in motor planning to coordinate sequential movements of the entire body. Input to these functional areas of cerebellar cortex come from the cerebral cortex, spinal cord, and brainstem by passing predominantly through the middle and inferior cerebellar peduncles. Fibers entering the cerebellum proceed as mossy fibers (from various regions) or climbing fibers (from olivary nucleus). Mossy fibers form excitatory synapses with dendrites of the granule cells, in the granule cell layer (eFig. 9.67). From here, the granule cells send axons to the molecular layer, where they bifurcate into parallel fibers that run longitudinally in the folia. The parallel fibers


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Anatomy_Gray. granule cell layer (eFig. 9.67). From here, the granule cells send axons to the molecular layer, where they bifurcate into parallel fibers that run longitudinally in the folia. The parallel fibers then synapse on Purkinje cells in the outermost Purkinje cell layer (eFig. 9.67). Climbing fibers project to the Purkinje cell layer and form powerful excitatory connections with the Purkinje cells. The Purkinje cells then project to the deep cerebellar nuclei (eFig. 9.67).


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Anatomy_Gray. As mentioned earlier, the cerebellum receives input from the cerebral cortex, brainstem, and spinal cord. Input from the cerebral cortex to the cerebellum is primarily involved in voluntary muscle control and coordination of movement. Axonal projections from the cerebral cortex destined for the cerebellum descend through the internal capsule and terminate on pontine nuclei (eFig. 9.68). The axons from the pontine nuclei then cross over as transverse fibers to enter the contralateral cerebellum through the middle cerebellar peduncle.


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Anatomy_Gray. Input from the spinal cord to the cerebellum conveys information from muscles and joints to influence muscle tone and posture. The primary spinal cord pathways with connections to the cerebellum include the anterior or ventral spinocerebellar and the posterior or dorsal spinocerebellar tracts. These tracts originate from joint and cutaneous mechanoreceptors and ascend through the spinal cord to enter the ipsilateral cerebellum primarily through the inferior cerebellar peduncle (eFig. 9.69). A final source of cerebellar input arises from the vestibular nuclei and reticular formation in the brainstem. The connections are primarily involved in reflexive maintenance of balance. These nuclei send axonal projections to the ipsilateral cerebellum through the inferior cerebellar peduncle.


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Anatomy_Gray. Output from the cerebellum originates from one of the four deep cerebellar nuclei. The largest collection of fibers leaving the cerebellum originates from the dentate nucleus. Axons from this nuclear complex project to the contralateral ventral nucleus of the thalamus after decussating in the superior cerebellar peduncle. From here, axons of the thalamic nuclei project to the motor cortex (eFig. 9.70). This pathway influences posture and movement.


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Anatomy_Gray. The emboliform and globose nuclei, or interposed nuclei, have a similar course as the axons from the dentate, but with the addition of another synaptic target. Axons from the interposed nuclei decussate in the superior cerebellar peduncle to synapse on the contralateral ventral nucleus of the thalamus and the contralateral red nucleus in the midbrain (eFig. 9.70). Axons leaving the red nucleus descend to the inferior olivary nucleus in the medulla. The axonal projections from the interposed nuclei function in monitoring and correcting motor activity of the upper and lower extremities.


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Anatomy_Gray. Axons from the fastigial nucleus project to the vestibular nuclei, reticular formation, contralateral ventral nucleus of the thalamus, and contralateral tectum. Vestibular axons pass through the inferior cerebellar peduncle to reach the ipsilateral vestibular nucleus and uncinate fasciculus to reach the contralateral vestibular nucleus (eFig. 9.70). Also going through the inferior cerebellar peduncle are axons heading to the reticular formation. Ascending in the superior cerebellar peduncles are axons that will synapse with the contralateral tectum and contralateral ventral nucleus of the thalamus.


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Anatomy_Gray. The cerebellum is perfused by the vertebrobasilar system of arteries (eFig. 9.42). Before merging and forming the basilar artery, each vertebral artery gives rise to a PICA and posterior spinal artery and contributes to the formation of the anterior spinal artery (eFig. 9.71). The PICA perfuses the inferior portion of the cerebellum. At the level of the caudal pons, the AICA branches off the basilar artery and perfuses the anterior and lateral portion of the cerebellum, as well as the middle and inferior cerebellar peduncles (eFig. 9.71). Just before the midbrain, the superior cerebellar arteries branch off of the basilar artery and supply the superior cerebellar peduncles and superior portion of the cerebellar hemispheres (eFig. 9.71). Part VIII: Visual System


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Anatomy_Gray. Part VIII: Visual System The visual system is a complex special sensory system that begins in the eyeball and has neuronal connections to the thalamus, brainstem, primary visual cortex, and association cortices. In addition to mediating visual perception, these connections are also involved in higher visual functions, such as determining spatial relationships between objects and structural features of objects. In this section we will explore the primary or geniculate visual pathway from the retina to the primary visual cortex.


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Anatomy_Gray. Although the retinal layer of the eyeball is often considered the beginning of visual perception, the anterior structures of the eye play an important role in visual perception too. The anteriormost structure is the cornea and is the first layer through which light, the visual stimulus, enters the eye (eFig. 9.72). This transparent layer overlies the aqueous humor of the anterior chamber and the pupil, a small central aperture that controls how much light is admitted into the eye. After passing through the pupil light is refracted through the lens, which along with the ciliary body, separates the anterior portion of the eye from the posterior portion (eFig. 9.72). The lens is a clear biconvex structure that rounds in shape as the ciliary muscle contracts and relaxes the suspensory ligaments attached to the borders of the lens, a parasympathetically controlled process referred to as accommodation.


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Anatomy_Gray. After the lens, light passes through the vitreous humor of the posterior chamber and is projected onto the layers of the retina (eFig. 9.73). The retina is composed of a non-neural layer and several layers of neural cells with synaptic connections. To reduce the amount of light reflected in the eye, the choroid layer lining the inner surface of the sclera (eFig. 9.72), along with the pigment epithelium layer (non-neural) of the retina, absorb and refract some of the light stimulus (eFig. 9.73). Interdigitating between the pigment epithelial cells, the photoreceptors transduce the light stimulus into an electrical signal in a process called phototransduction. Images formed on the retina are inverted in both vertical and lateral dimensions (eFig. 9.74). Because of this, the visual field is defined as having four quadrants: left/right and upper/lower.


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Anatomy_Gray. Photoreceptors include rods, which are very sensitive to light and essential for vision in dimly lit conditions, and cones, which are responsible for color vision and high visual acuity. Although rods and cones are both distributed across the retina, rods outnumber cones by twentyfold and are concentrated in the periphery of the retina. Cones predominate near the macula and are the only photoreceptors present at the fovea (eFig. 9.72). The fovea represents the primary visual axis of the eye and is the location of maximal visual acuity. Despite their functional differences, both the rods and cones have an outer light-sensing segment, an inner segment, and a synaptic terminal. These synaptic terminals contact bipolar cells, the first-order neurons in the visual pathway (eFig. 9.73). Bipolar cells then synapse with ganglion cells, the second-order neurons in the visual pathway. Two other cell types present in the retina are horizontal and amacrine cells. These transversely oriented


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Anatomy_Gray. cells then synapse with ganglion cells, the second-order neurons in the visual pathway. Two other cell types present in the retina are horizontal and amacrine cells. These transversely oriented interneurons moderate the excitation level of bipolar and ganglion cells.


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Anatomy_Gray. Axons from the ganglion cells coalesce at the optic disc, which is absent of photoreceptors and thus creates a blind spot in the visual field. As they leave the optic disc they form the optic nerve, acquire a myelin sheath provided by oligodendrocytes, and are invested by the cranial meninges (eFig. 9.72). These morphological features derived during embryonic development, define the optic nerve as a component of the CNS. Anterior to the infundibular stalk, the optic nerves converge at the optic chiasm. Within the chiasm, axons from the nasal portion of the retina decussate and enter into the contralateral optic tract (eFig. 9.75). Conversely, axons from the temporal portion of the retina stay ipsilateral to enter the ipsilateral optic tract (eFig. 9.75).


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Anatomy_Gray. Continuing posteriorly, the optic tracts course around the midbrain to enter the lateral geniculate nucleus of the thalamus (eFig. 9.75). At this level, a small portion of the fibers from the optic tract travel to the pretectal area and superior colliculus to mediate the pupillary light reflex. Axons leaving the lateral geniculate nucleus form the optic radiations, which continue on to the primary visual cortex in the occipital lobe (eFig. 9.76). Fibers traveling in the lower portion of the optic radiations terminate on the lower half of the primary visual cortex, whereas fibers in the upper portion terminate on the upper half of the cortex (eFig. 9.76). A full review of how the visual field is represented throughout the visual pathway can be reviewed in eFig. 9.77.


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Anatomy_Gray. As mentioned previously, images formed on the retina are inverted in both vertical and lateral dimensions. In addition, the fibers from the nasal portion of the hemiretina decussate at the optic chiasm. Because of this, the optic tracts, thalamus, optic radiations, and primary visual cortex receive information relating only to the contralateral half of the visual field. Knowledge of how the visual field is represented throughout the visual pathway is essential for identifying the location of lesions in patients with visual field deficits. Examples of lesions in the five major structures of the visual pathway (optic nerve, optic chiasm, optic tract, optic radiations, primary visual cortex) and their associated visual field deficits are represented in eFig. 9.78. Part IX: Auditory and


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Anatomy_Gray. Part IX: Auditory and Cranial nerve VIII, the vestibulocochlear nerve, conveys sensory information from the vestibular and auditory organs of the inner ear to the pontomedullary junction of the brainstem. Although these sensory modalities are conveyed to the brainstem by a common nerve bundle, each of these sensory functions has different central pathways. In this section we will first review the central auditory pathways and then the vestibular pathways.


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Anatomy_Gray. Sound waves, the auditory stimulus, are directed toward the external acoustic meatus by the pinna of the outer ear and through the ear canal to the tympanic membrane (eFig. 9.79). Vibration of the tympanic membrane, induced by the incoming sound waves, is transmitted to the three ossicle bones (malleus, incus, and stapes) of the middle ear. These bones amplify sound waves so they can be converted to pressure waves at the oval window of the fluid-filled cochlea. To prevent damage from loud or high-decibel sounds, movements of the malleus and stapes are reduced by the tensor tympani and stapedius muscles.


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Anatomy_Gray. In the cochlea, sound waves are converted into an electrical signal at the organ of Corti. The organ of Corti rests upon the basilar membrane in the scala media, which is filled with endolymph (eFig. 9.80). In addition to contributing to the formation of the scala media with the vestibular membrane, the basilar membrane separates the cochlea into the scala vestibuli and scala tympani, which are filled with perilymph and are continuous with one another at the helicotrema (eFig. 9.80).


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Anatomy_Gray. As the sound waves move through the perilymph they displace the basilar membrane, which causes deflection of the hair cells in the organ of Corti (eFig. 9.81A). These sensory receptors synapse with sensory neurons, which have cell bodies in spiral ganglion located within the modiolus of the cochlea (eFig. 9.80). Axons leaving the modiolus form the cochlear nerve near the base of the cochlea. The cochlear nerve then passes through the internal acoustic meatus and subarachnoid space to enter the pontomedullary junction at the cerebellopontine angle.


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Anatomy_Gray. The first-order axons entering the brainstem from the cochlea terminate ipsilaterally on the dorsal and ventral cochlear nuclei. From here, second-order axons have several synaptic targets. Second-order axons forming the ascending auditory pathway ascend to the pons and project bilaterally on the superior olivary nucleus (eFig. 9.82). These bilateral projections are important for auditory acuity and localizing the origin of a sound. From here, fibers continue to ascend as the lateral lemniscus and terminate in the inferior colliculus of the midbrain. Axons leaving the inferior colliculus then have a synaptic relay in the medial geniculate nucleus of the thalamus before reaching the final synaptic target: the primary auditory cortex (superior temporal gyrus) of the temporal lobe (eFig. 9.82). Throughout this pathway, from the basilar membrane to the primary auditory cortex, auditory stimuli are tonotopically represented. This is analogous to the somatotopic map previously discussed in


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Anatomy_Gray. Throughout this pathway, from the basilar membrane to the primary auditory cortex, auditory stimuli are tonotopically represented. This is analogous to the somatotopic map previously discussed in the section on somatosensory systems pathways.


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Anatomy_Gray. In addition to the ascending auditory pathway, the superior olivary nucleus receives descending input from the primary auditory cortex as a form of feedback (eFig. 9.82). The superior olivary nucleus then sends descending olivocochlear fibers to the organ of Corti, which has an inhibitory function on the hair cells to prevent damage from harmfully loud sounds. It is also believed that the superior olivary nucleus has connections with the motor nuclei of the trigeminal and facial nerve to mediate reflexive contraction of the tensor tympani and stapedius muscles in response to loud sounds.


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Anatomy_Gray. The vestibular nerve transmits afferent or sensory information regarding movement and position of the head from the vestibular organs, which include semicircular ducts, utricle, and saccule. Like the cochlear apparatus, each of these vestibular organs is located within a membranous (ductal) portion of the vestibular apparatus, which is surrounded by a bony (canal) portion (eFig. 9.83). The cell bodies for these sensory receptors are located in the vestibular (Scarpa’s) ganglion within the internal acoustic meatus (eFig. 9.83). The vestibular nerve then passes through the internal acoustic meatus and subarachnoid space to enter the pontomedullary junction at the cerebellopontine angle.


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Anatomy_Gray. The central processes of the vestibular axons predominantly terminate in the four vestibular nuclei (superior, inferior, medial, and lateral), which are located in the rostral medulla and caudal pons (eFig. 9.40). Axons leaving the vestibular nuclei have several ascending and descending synaptic targets. These pathways connect with visual motor, descending motor, and cerebellar pathways to coordinate movement and maintain posture and balance (eFig. 9.84).


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Anatomy_Gray. Axons ascending after leaving the vestibular nuclei form the medial longitudinal fasciculus to reach the oculomotor, trochlear, and abducent nuclei (eFig. 9.85). These connections coordinate movement of the head and eyes so that visual fixation on an object can be maintained. Other axons ascending from the vestibular nuclei project to the cerebral cortex after a synaptic relay in the ventral posterior nucleus of the thalamus (eFig. 9.84B). This connection assists in consciously orienting oneself in space. In addition to these connections, axons leaving the vestibular nuclei pass through the inferior cerebellar peduncle to reach the cerebellum and modulate equilibrium (eFig. 9.84B).


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Anatomy_Gray. Axons descending after leaving the vestibular nuclei form the medial and lateral vestibulospinal tracts ipsilaterally (eFig. 9.84B). As mentioned in the previous section on medial motor systems in the spinal cord, the axons in these pathways synapse on interneurons within the anterior horn gray matter to influence spinal motor neuron activity and maintain posture and balance. Part X: Hypothalamus The hypothalamus is a neuroendocrine organ that regulates physiological processes for survival such as consumption of fluid and food, temperature control, the sleep–wake cycle, growth, and reproduction. As a result of this vast array of functions, the nuclei of the hypothalamus make connections with several other neural and endocrine structures in the body (eFig. 9.86). In this section we will explore the nuclei of the hypothalamus and their main connections.


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Anatomy_Gray. Located in the ventralmost aspect of the diencephalon, the hypothalamus is bounded by the lamina terminalis anteriorly, the hypothalamic sulcus superiorly, and the tegmentum of the midbrain posteriorly (eFig. 9.87). Laterally the hypothalamus is bordered by the substantia innominata rostrally and the posterior limb of the internal capsule caudally. It forms the floor in addition to the lower portion of the lateral walls in the third ventricle. When viewing the external surface of the ventral brain, the area containing the hypothalamus is circumscribed by the optic chiasm, optic tract, crus cerebri, and caudal edge of the mammillary bodies (eFig. 9.88).


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Anatomy_Gray. Continuous with the hypothalamus inferiorly is the pituitary gland. These two structures are connected by the infundibulum and hypophysial stalk just caudal to the optic chiasm (eFig. 9.87). The intimate relationship of the hypothalamus to the portal circulation of the pituitary gland allows the hypothalamus to be an efficient regulator of hormone synthesis and release. Releasing and inhibiting factors synthesized by the hypothalamus pass through these portal vessels via the tuberoinfundibular tract (eFig. 9.89) to reach the anterior pituitary (adenohypophysis) and control release of hormones produced by the anterior pituitary such as adrenocorticotropic hormone, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, growth hormone, and prolactin (eFig. 9.90).


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Anatomy_Gray. A second connection exists between the hypothalamus and pituitary through nerve fibers, which originate in the supraoptic region and paraventricular nuclei of the medial hypothalamus and extend through the hypothalamohypophyseal tract to the posterior lobe of the pituitary for release into the circulatory system (eFig. 9.89). Internally, the hypothalamus is composed of many small nuclei, which are divided by a parasagittal plane into a medial and lateral zone. Landmarks for this dividing point are the columns of the fornix and the mammillothalamic tract as they reside within this sagittal plane (eFig. 9.91). The hypothalamus is also divided by coronal planes into a preoptic area and periventricular zone. Note that the periventricular zone is not to be confused with the paraventricular nucleus, which is a thin region of cell bodies lying medial to the medial zone.


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Anatomy_Gray. Within the lateral zone of the hypothalamus is a large bundle of axons forming the medial forebrain bundle (MFB) (eFig. 9.90). Theses fibers interconnect the hypothalamus with the septal nuclei rostrally and nuclear complexes within the brainstem. Axons arising from the large lateral nucleus in this zone enter the MFB and function in promoting feeding behavior. The other and smaller nuclear group in this zone is the tuberal group. Axons from the tuberal nuclei make connections with the anterior pituitary through the tuberoinfundibular tract to regulate release of hormones in the hypophysial portal system and to the cerebellum to regulate motor activity (eFig. 9.89).


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Anatomy_Gray. The medial zone is divided into three regions: supraoptic, tuberal, and mammillary. There are four nuclei in the supraoptic region, which play a role in thermoregulation, osmoregulation, and the sleep–wake cycle. The supraoptic and paraventricular nuclei in this region synthesize antidiuretic hormone or vasopressin, which stimulates water uptake and oxytocin for stimulation of uterine contractions and lactation in the mammary glands. Axons from these nuclei are conveyed by the hypothalamohypophyseal tract to the posterior pituitary for release into the circulatory system (eFig. 9.89). A third nuclear group in this region is the suprachiasmatic nucleus. This nucleus receives input directly from the retina to influence circadian rhythms, which contribute to the light–dark cycle. The anterior nucleus is the final group and functions predominantly in regulating body temperature.


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Anatomy_Gray. The tuberal region in the medial zone contains three nuclei: ventromedial, dorsomedial, and arcuate. The largest and best defined is the ventromedial nucleus, which functions as a satiety center to decrease feeding behavior. Posterior to the ventromedial nucleus is the dorsomedial nucleus, which functions in the behavioral expression of rage or aggressive behavior. Finally, the arcuate nucleus serves as a center for releasing hormones, which are transmitted by the tuberoinfundibular tract and hypophysial portal system to the anterior pituitary (eFig. 9.89).


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Anatomy_Gray. The mammillary region or mammillary body is the final group of nuclei in the medial zone. Four nuclei comprise this region: medial, intermediate, lateral mammillary, and posterior hypothalamic. The best defined is the medial mammillary nucleus, as it is the primary site for the termination of axons from the postcommissural fornix. This pathway originates from the subiculum of the hippocampal complex and plays a key role in memory. The medial mammillary nuclei also connects to structures of the limbic system. The periventricular zone resides medial to the medial zone and adjacent to the ependymal cells of the third ventricle. Neurons from this zone predominantly synthesize releasing hormones. Axons from these neuronal cells project through the tuberoinfundibular tract to the hypophysial portal system to influence release of hormones from the anterior pituitary.


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Anatomy_Gray. Through the review of the hypothalamus thus far, it is apparent that this small, 4-gram structure has a significant role in regulating visceral, endocrine, and behavioral system functions through multiple pathways. It is important to remember the majority of the pathways mentioned represent input–output relationships between the hypothalamus and other structures. For a review of neural and non-neural inputs and outputs, refer to the summary figures (eFig. 9.92A and B). Part XI: Olfactory and


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Anatomy_Gray. Part XI: Olfactory and The sense of olfaction has a role in both pleasurable experiences and survival. The same receptors that allow us to enjoy the food we consume or experience odorants in the environment also help us avoid spoiled food or potentially hazardous situations like a fire. Unlike the other special sensory system pathways, the olfactory sensory pathway is unique in that it does not have a thalamic relay before reaching the primary olfactory cortex. In this section we will review the course of the neurons in the olfactory system and their connection to the limbic system.


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Anatomy_Gray. Three types of olfactory receptors make up the olfactory epithelium along the lateral and septal walls of the nasal cavity. These cells allow for regeneration (basal stem cells), support (sustentacular cells), and transmission of information (olfactory receptor neurons). Each olfactory receptor neuron has an olfactory vesicle with cilia that contain receptors for odorant molecules and an unmyelinated axon that passes through the cribriform plate to terminate in the olfactory bulb (eFig. 9.93). As the olfactory receptor neurons originate embryologically from the CNS, they are considered part of the CNS and not the PNS.


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Anatomy_Gray. After synapsing with the mitral cells in the glomeruli of the olfactory bulb, mitral cell axons converge to form the olfactory tract. The olfactory tract then divides into medial and lateral olfactory striae to reach different synaptic targets (eFig. 9.94). Some of the axons in the medial olfactory striae travel through the diagonal band to reach the septal area, whereas others cross the midline in the anterior commissure and inhibit mitral cell activity in the contralateral olfactory bulb to enhance localization of the olfactory stimulant. Axons in the lateral olfactory stria primarily terminate in the piriform cortex/primary olfactory cortex of the uncus and in the amygdala (eFig. 9.94). The medial forebrain bundle, traveling through the lateral hypothalamus, connects the olfactory cortex with both the hypothalamus and the brainstem to regulate autonomic responses such as arousal through the reticular formation, salivation, and gastric contraction.


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Anatomy_Gray. The limbic system is composed of several cortical and subcortical structures that participate in an intricate network of connections to regulate complicated behaviors such as memory, emotions, homeostatic functions, and motivational state. In this section we will review the major structures and pathways that form the limbic system. Grossly, the limbic lobe includes a ring-shaped area of cortical structures that border the brainstem. These cortical areas include the cingulate gyrus, parahippocampal gyrus, and subcallosal area (eFig. 9.12). Laterally, the insular cortex also participates in limbic system function (eFig. 9.10). Nuclear structures of the limbic system include the amygdala, hippocampal formation, anterior and mediodorsal thalamic nuclei, septal nuclei in the forebrain, and nucleus accumbens (eFig. 9.95).


Anatomy_Gray

Anatomy_Gray. The amygdaloid nucleus is an almond-shaped structure located anterior to the inferior horn of the lateral ventricle and tail of the caudate within the temporal lobe (eFig. 9.96). Structurally, the amygdala consists of three nuclear regions: a large basolateral group and a smaller corticomedial group, which includes the central nucleus. Functionally, the amygdala is primarily associated with the emotion of fear, but it also has an important role in autonomic and neuroendocrine pathways. Connections of the amygdala are predominantly bidirectional and follow three different pathways: the uncinate fasciculus, stria terminalis, and ventral amygdalofugal pathway (eFig. 9.97). Connections to cortical areas pass through the uncinate fasciculus, which progresses anterior to the amygdala. Projections to the septal area and hypothalamus follow the stria terminalis (eFig. 9.98A–D). Fibers forming the ventral amygdalofugal pathway project to thalamic nuclei and several brainstem and forebrain


Anatomy_Gray

Anatomy_Gray. to the septal area and hypothalamus follow the stria terminalis (eFig. 9.98A–D). Fibers forming the ventral amygdalofugal pathway project to thalamic nuclei and several brainstem and forebrain structures (eFig. 9.98A–D).


Anatomy_Gray

Anatomy_Gray. The nucleus accumbens resides with the ventral forebrain adjacent to where the putamen and head of the caudate become continuous with one another (eFig. 9.99). Afferent axons to the nucleus accumbens come from the amygdala through the amygdalofugal pathway, hippocampal formation by way of the fornix, basal forebrain area from the stria terminalis, and ventral tegmentum through the medial forebrain bundle (eFig. 9.98A–D). Efferent axons leaving the nucleus accumbens project directly to the hypothalamus and globus pallidus and reach nuclei in the brainstem through the medial forebrain bundle. Its connections to the globus pallidus represent an important connection of the limbic system to the motor system. The overall function of the nucleus accumbens is recognized as a gratification center and has been shown to play a role in behaviors related to addiction.


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Anatomy_Gray. The septal region is located rostral to the anterior commissure along the medial aspect of the cerebral hemispheres (eFig. 9.99). This region appears to play a role in pleasurable behaviors. Conversely, lesion studies indicate that damage to this area evokes behaviors of extreme displeasure or rage. Afferent axons to the septal area arise from the amygdala, hippocampus, olfactory tract, and monoaminergic nuclei in the brainstem (eFigs. 9.100 and 9.101). The septal area also connects to a collection of cholinergic neurons along the wall and roof of the third ventricle known as the habenular nuclei. Axons from the habenular nuclei project to the interpeduncular nucleus of the reticular formation, which is believed to play a role in the sleep–wake cycle (eFig. 9.100).


Anatomy_Gray

Anatomy_Gray. The hippocampal formation is located in the medial ventral temporal lobe (eFig. 9.102). It consists of the hippocampus, dentate gyrus, and subiculum (eFig. 9.103A and B). The hippocampal formation plays a role in memory processes such as episodic memory, short-term memory, working memory, and consolidation of memories. Input to the hippocampal formation is primarily received by the entorhinal cortex from association cortices. Because of this, it is believed that the “storage” of memories is in the association and primary cortices, not in the medial temporal lobe. Neurons from the entorhinal cortex project to the hippocampal formation by two pathways: the perforant pathway and alvear pathway. The perforant courses directly through the hippocampal sulcus to reach the dentate gyrus (eFig. 9.104B). As the hippocampus resembles the appearance of a ram’s horn, early on it was named cornu ammonis (horn of Ammon). Based on its cytoarchitecture, it was subdivided into four regions termed the


Anatomy_Gray

Anatomy_Gray. As the hippocampus resembles the appearance of a ram’s horn, early on it was named cornu ammonis (horn of Ammon). Based on its cytoarchitecture, it was subdivided into four regions termed the cornu ammonis 1 to 4 (eFig. 9.104A). From the dentate gyrus, axons project to CA3 of the hippocampus. Axons from the hippocampus leave via the fornix or as Shaffer collaterals to reach CA1. Axons from CA1 may enter the fornix or project to the subiculum. Finally, axons from the subiculum enter the fornix or go back to the entorhinal cortex.


Anatomy_Gray

Anatomy_Gray. A second afferent pathway from the entorhinal cortex to the hippocampal formation is through the alvear pathway. Axons in the alvear pathway project directly on to CA1 and CA3 of the hippocampus (eFig. 9.104B). Similar to the perforant pathway, axons leaving the alvear pathway primarily originate from CA1 and CA3, which then project to the subiculum.


Anatomy_Gray

Anatomy_Gray. Efferent axons leaving the hippocampal formation primarily exit from the subiculum and form the fornix (Latin for “arch”), a white matter structure that arches over the ventricular system (eFig. 9.95). The fornix begins with axons exiting the hippocampus to form the alveus along the ventricular surface of the hippocampus. As the axons come together medially, they form a bundle referred to as the fimbria of the fornix. The fornix then emerges from the hippocampal formation and curves under the corpus callosum before coursing medially to run adjacent to the midline (eFig. 9.105). At the anterior commissure, the fornix divides into a precommissural fornix and postcommissural fornix to reach the nucleus accumbens, septal nuclei, medial frontal cortex, mammillary nucleus, ventromedial nucleus of the hypothalamus, and anterior nucleus of the dorsal thalamus (eFig. 9.95).


Anatomy_Gray

Anatomy_Gray. Through this section we have described a collection of anatomical structures and defined their connections with other areas of the brain and brainstem without exploring how these individual structures are interconnected with one another. In the 1930s James Papez, an American neurologist, described a circuit that links these structures and cortical areas together in a way that was thought to be involved in the experience and expression of emotion. This is referred to as the Papez circuit (eFig. 9.106). The circuit begins with fibers from the subiculum, which then enter the fornix to reach the mammillary nuclei. These axons then project through the mammillothalamic tract to the anterior nucleus of the thalamus. Next, the axons from the anterior nucleus of the thalamus project through the internal capsule to the cingulate gyrus. Lastly, the cingulum fibers from the cingulate cortex project to the parahippocampal gyrus and then the entorhinal cortex and hippocampal formation (eFig.


Anatomy_Gray

Anatomy_Gray. the internal capsule to the cingulate gyrus. Lastly, the cingulum fibers from the cingulate cortex project to the parahippocampal gyrus and then the entorhinal cortex and hippocampal formation (eFig. 9.106). Papez’s description of this circuit is useful for reviewing the major limbic system pathways; however, the role of some of the structures in the pathway has been shown to play little or no role in the expression of emotion. In addition, many of the structures that do play a role in the expression of emotion also have a role in other functions.