The central nervous system (CNS) has a crucial role in the maintenance of energy homeostasis by orchestrating a plethora of signals from peripheral organs about the state of energy stores and the current energy intake needed to match energy expenditure. These signals converge into the hypothalamic regions and its complex local circuitry.
CNS-derived cholecystokinin (CCK) at central level modulates energy balance by regulating neuronal activity of hypothalamic neurons that regulate food intake, energy storage and consumption. Moreover, our recent work has identified CCK neurons as a novel and critical cellular component of the HPA axis, and has shown a requirement for TrkB signalling in the transmission of glucocorticoid signalling (Geibel M. et al, (2014), Nat Commun). However, the source of endogenous CCK, the function of CCK neurons in the hypothalamus, as well as their potential role in the network dynamics regarding energy homeostasis has not been elucidated.
My project seeks to understand the role of CCK neurons in hypothalamic circuits by combining state-of-the-art mouse genetic tools with stereotactic intracranial delivery of adeno-associated viruses that results in cell-type specific synaptic silencing, or by chemogenetic inhibition of these neurons.