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. Much insight has been gained recently 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 positive and negative emotional learning and expression in a new world primate, the common marmoset. Since emotional responses are composed of both physiological and behavioural components we use an automated telemetry system to allow the simultaneous measurement of behavioural and autonomic e.g. heart rate and blood pressure, emotional responses in freely moving marmosets. This also helps bridge the gap between current human and rodent studies in which the primary measures of emotional expression are autonomic activity and behaviour, respectively. So far we have identified the critical role of the orbitofrontal cortex in the regulation of both positive (Reekie et al, 2008) and negative (Agustin-Pavon et al, 2012) emotional responses, responses that we have already shown to be dependent upon the amygdala. Lesions of the OFC not only disrupt the contextual regulation of autonomic and behavioural emotional responses as contingencies in the environment change but also lead to their uncoupling, an effect that could have a major impact on overall levels of emotionality. A separate contribution is also made by the ventrolateral PFC. In addition, we have identified the critical role of serotonin in modulating the processing of positive and negative feedback within the amygdala and ventral PFC, dissociating it’s role from that of dopamine. More recently, we have begun to explore prefronto-amygdala circuits in the context of individual differences in both genes and behavioural traits. It has been hypothesised that high trait anxiety and the 5-HT transporter polymorphism may act as vulnerability factors for developing neuropsychiatric disorders and so, using structural MRI, microPET and microdialysis we have begun to identify alterations in the prefronto-amygdala network in marmosets that are related to these individual differences.
Physiology 2012 (Edinburgh) (2012) Proc Physiol Soc 27, SA80
Research Symposium: Contribution of ventral prefrontal cortex to the regulation of amygdala-dependent negative and positive emotions
A. Roberts1
1. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.