Prefrontal circuits underlying anxiety and anhedonia: studies of emotion regulation in a primate.
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). Altered activity in serotoninergic forebrain systems has also been implicated and currently, the front-line treatment of these disorders includes drugs that target the serotonin system. However, our understanding of the interaction between these brain structures, and their modulation by serotonin, in the control and regulation of emotion is only in its infancy. 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 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. These regions are at their most highly developed in primates and thus, to further our understanding of the regulation of amygdala-dependent emotional learning and expression by the ventral PFC 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 two main experimental strategies. The first, to determine the effects of localized prefrontal manipulations on emotional states and the activity of downstream targets, the latter via fluorodeoxyglucose microPET. The second, by studying 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. Recent review: Shiba et al (2016) Frontiers in Systems Neuroscience 10:12.