Better understanding of affective behaviour through functional dissection of ventral subicular circuitry. (360G-Wellcome-109360_Z_15_Z)

The overall aim of the proposed work is to understand the control of affective behaviour, from the level of individual synaptic and cellular mechanisms through to the complex circuitry in which they are utilised. To achieve this I will investigate the ventral subiculum (vS). vS is considered crucial for affective behaviour, but due in part to its complex circuitry, how it carries out this important role is unknown. I will use a powerful combination of in vivo and in vitro circuit analysis to gai n a mechanistic understanding of how affective behaviour is controlled by vS circuitry, and altered by disease. I will first address the long-standing, but poorly tested hypothesis that distinct populations of projection neurons in vS have disparate and unique roles in the generation of affective behaviour using in vivo imaging and optogenetics. I will then investigate the afferent circuitry in vS that determines the activity of the different vS projection types, to provide a mechanistic m odel for how vS circuitry, and thus affective behaviour, is controlled. Finally, I will investigate cocaine-induced synaptic alterations in vS, and aim to provide a direct and mechanistic link between classically observed synaptic changes, circuit function and pathological behaviour.