Stimulation of entorhinal cortex-dentate gyrus circuitry is antidepressive.
Nat Med
; 24(5): 658-666, 2018 05.
Article
in En
| MEDLINE
| ID: mdl-29662202
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Entorhinal Cortex
/
Dentate Gyrus
/
Antidepressive Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Med
Journal subject:
BIOLOGIA MOLECULAR
/
MEDICINA
Year:
2018
Document type:
Article
Affiliation country:
Estados Unidos