Stimulation of entorhinal cortex-dentate gyrus circuitry is antidepressive.

Yun S, Reynolds RP, Petrof I, White A, Rivera PD, Segev A, Gibson AD, Suarez M, DeSalle MJ, Ito N, Mukherjee S, Richardson DR, Kang CE, Ahrens-Nicklas RC, Soler I, Chetkovich DM, Kourrich S, Coulter DA, Eisch AJ
Nat Med. 2018 24 (5): 658-666

PMID: 29662202 · PMCID: PMC5948139 · DOI:10.1038/s41591-018-0002-1

Major depressive disorder (MDD) is considered a 'circuitopathy', and brain stimulation therapies hold promise for ameliorating MDD symptoms, including hippocampal dysfunction. It is unknown whether stimulation of upstream hippocampal circuitry, such as the entorhinal cortex (Ent), is antidepressive, although Ent stimulation improves learning and memory in mice and humans. Here we show that molecular targeting (Ent-specific knockdown of a psychosocial stress-induced protein) and chemogenetic stimulation of Ent neurons induce antidepressive-like effects in mice. Mechanistically, we show that Ent-stimulation-induced antidepressive-like behavior relies on the generation of new hippocampal neurons. Thus, controlled stimulation of Ent hippocampal afferents is antidepressive via increased hippocampal neurogenesis. These findings emphasize the power and potential of Ent glutamatergic afferent stimulation-previously well-known for its ability to influence learning and memory-for MDD treatment.

MeSH Terms (17)

Animals Antidepressive Agents Behavior, Animal Chronic Disease Dendrites Dentate Gyrus Entorhinal Cortex Glutamates HEK293 Cells Humans Membrane Proteins Mice, Inbred C57BL Mice, Knockout Nerve Net Neurogenesis Peroxins Stress, Psychological

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