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Neuron. 2017 Aug 2;95(3):564-576.e4. doi: 10.1016/j.neuron.2017.06.044. Epub 2017 Jul 20.

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

Author information

1
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA.
2
Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
3
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA. Electronic address: greengard@rockefeller.edu.

Abstract

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.

KEYWORDS:

5-HT1BR; 5-HT2AR; CCK; PV; SSRI; TRAP; antidepressants; hippocampus; p11

PMID:
28735749
DOI:
10.1016/j.neuron.2017.06.044
[Indexed for MEDLINE]
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