Sex-specific GABAergic microcircuits that switch vulnerability into resilience to stress and reverse the effects of chronic stress exposure DOI Creative Commons
Tong Jiang, Mengyang Feng,

Alexander Hutsell

et al.

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

Sex-specific GABAergic microcircuits that switch vulnerability into resilience to stress and reverse the effects of chronic stress exposure DOI Creative Commons
Tong Jiang, Mengyang Feng,

Alexander Hutsell

et al.

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

Citations

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