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Dysregulated emotions are a core feature of many neuropsychiatric disorders and are often associated with altered activity in limbic emotional circuitry that includes the amygdala, hippocampus and prefrontal cortex (PFC).  Front line treatments include drugs that target the serotonin system and more recently the glutamate system, but how they work, and in which patient, is poorly understood. Recently, much insight has been gained into the role of the medial PFC in the regulation of the amygdala-dependent freezing response to a fear conditioned stimulus, primarily from studies in rodents. However, the comparability of medial PFC across rodents and primates, including humans, is far from clear. Moreover, the neuroimaging of patients with mood and anxiety disorders have revealed structural and activity changes not only in the medial but also the ventral PFC, including orbitofrontal and ventrolateral PFC. All these regions are at their most highly developed in primates and thus, to further our understanding of the prefrontal regulation of amygdala-dependent emotional learning and we have developed models of negative and positive emotional learning and expression in a new world primate, the common marmoset. Since emotional states are composed of both physiological and behavioural components we use an automated telemetry system to allow the simultaneous measurement of behavioural and cardiovascular emotional responses e.g. heart rate and blood pressure, in freely moving marmosets. We employ three main experimental strategies. The first, to determine the effects of localized prefrontal manipulations on emotional states, their impact on activity in downstream targets using fluorodeoxyglucose microPET and their sensitivity to drugs targeting the glutamate and serotonin system. Second, we have initiated a neuroimaging program to characterize the development of prefrontal circuits across childhood and adolescence in the marmoset since the majority of anxiety and mood disorders have their onset during these critical periods of development in humans. The third, to study the impact of known behavioural and genetic risk factors for mood and anxiety disorders, i.e. trait anxiety and a polymorphism in the upstream promotor region of the serotonin transporter gene, on these prefrontal circuits using microPET, structural mri, microdialysis and post mortem mRNA analysis. The first two strategies will be the focus of this presentation.

Recent review: Shiba et al (2016) Frontiers in Systems Neuroscience 10:12.

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