ELSC Seminar Series

Depression is a common psychiatric condition and is a leading cause of disability worldwide. The poor understanding of the pathophysiology of depression has translated to limited development of new pharmacotherapies; unfortunately, more than 30% of patients are still considered treatment-resistant.
Thus, there is an urgent need to identify the molecular mechanisms underlying depression and to develop effective novel, targeted antidepressants. Accumulating data strongly implicate the dysfunction of hippocampal inhibitory interneurons (INs) in human and rodent depression. Hence, targeting these neurons has great potential to alleviate depression, leading to the development of novel cell-typespecific psychotherapies. Recently, we identified Neurensin-2 as a novel modulator of hippocampal inhibitory neuron function and as a potent mediator of depressive-like behavior.
Neurensin-2 is a vesicular protein selectively expressed in the subtypes of hippocampal inhibitory neurons, including cholecystokinin (CCK) neurons. Overexpression of Neurensin-2 in CCK neurons results in altered neuronal function and profound depressive-like behaviors. However, the molecular mechanisms by which Neurensin-2 modulates behavior are currently unknown. In my talk, I will present novel findings providing evidence that Neurensin-2 regulates the expression and function of cannabinoid receptor 1 (CBR1) and will discuss how this new regulatory pathway may mediate depression and anxiety in a celltype-specific manner.