
Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 16, 2024
Clinical and preclinical studies have identified somatostatin (SST)-positive interneurons as critical elements that regulate the vulnerability to stress-related psychiatric disorders. Conversely, disinhibition of SST neurons in mice results resilience behavioral effects chronic stress. Here, we established a low-dose chemogenetic protocol map these changes positively negatively motivated behaviors specific brain regions. AAV-hM3Dq-mediated activation prelimbic cortex (PLC) had antidepressant drug-like on anxiety- anhedonia-like male but not female mice. Analogous manipulation ventral hippocampus (vHPC) such Moreover, PLC vHPC resulted stress resilience. Activation reversed prior stress-induced defects behavior males was ineffective females. alterations females males. Quantitation c-Fos+ FosB+ stress-exposed revealed leads paradoxical increase pyramidal cell activity. Collectively, data demonstrate GABAergic microcircuits driven by dendrite targeting enable sex- brain-region-specific neural plasticity promotes reverses behavior. The provide rationale for lack efficacy benzodiazepines superior dendrite-targeting, low-potency GABAA receptor agonists, independent sex despite striking differences relevant substrates.
Language: Английский