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Publication : Initiation of Behavioral Response to Antidepressants by Cholecystokinin Neurons of the Dentate Gyrus.

First Author  Medrihan L Year  2017
Journal  Neuron Volume  95
Issue  3 Pages  564-576.e4
PubMed ID  28735749 Mgi Jnum  J:256106
Mgi Id  MGI:6114536 Doi  10.1016/j.neuron.2017.06.044
Citation  Medrihan L, et al. (2017) Initiation of Behavioral Response to Antidepressants by Cholecystokinin Neurons of the Dentate Gyrus. Neuron 95(3):564-576.e4
abstractText  Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used class of antidepressant drugs, but the cellular and molecular mechanisms by which their therapeutic action is initiated are poorly understood. Here we show that serotonin 5-HT1B receptors in cholecystokinin (CCK) inhibitory interneurons of the mammalian dentate gyrus (DG) initiate the therapeutic response to antidepressants. In these neurons, 5-HT1B receptors are expressed presynaptically, and their activation inhibits GABA release. Inhibition of GABA release from CCK neurons disinhibits parvalbumin (PV) interneurons and, as a consequence, reduces the neuronal activity of the granule cells. Finally, inhibition of CCK neurons mimics the antidepressant behavioral effects of SSRIs, suggesting that these cells may represent a novel cellular target for the development of fast-acting antidepressant drugs.
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