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全脳レベルの活動・回路マッピングから解き明かすストレス脳

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1-S08-2

Whole-brain mapping of activated neurons and circuits in brains after

exposure to acute stressors

Misaki Niu

1

, Atsushi Kasai

1

, Kaoru Seiriki

1,2

, Hitoshi Hashimoto

1,3,4,5,6

1

Lab. Mol. Neuropharmacol., Grad. Sch. Pharmaceut. Sci., Osaka Univ., 2Inst. Transdiscip. Grad. Degree Prog., Grad. Sch. Pharmaceut. Sci., Osaka Univ., 3Unit. Grad. Sch. Child Dev., Osaka Univ., 4Inst. Datability Sci., Osaka Univ., 5Open Tarnsdiscip. Res. Initi., Osaka Univ., 6Dep. Mol Pharmaceut. Sci., Grad. Sch. Med., Osaka Univ.

The processing of stress responses involves brain-wide communication among cortical and subcortical regions. Although considerable effort has been made to discover these brain regions, hypothesis-free and unbiased approaches to identify previously unknown neural elements have been limited until recently due to technical limitations. Here, we performed whole-brain activation mapping and machine learning-based analyses to identify previously uncharacterized brain regions and neuronal ensembles implicated in stress, and found that the claustrum (CLA) most prominently contributes to discrimination in stressed brains. Activity-dependent genetic labeling in TRAP2 mice subjected to social defeat stress revealed reciprocal connection of the CLA with fos-tagged neurons in brain-wide areas, including the basolateral amygdala and medial prefrontal cortex. Chemogenetic reactivation of the fos-tagged CLA neuronal ensemble reproduced anxiety-like behaviors and brain-wide neuronal activation, while its silencing attenuated anxiety-like behaviors induced by acute social defeat stress and increased resistance to chronic social defeat stress. The CLA thus controls stress-induced emotional responses bidirectionally through brain-wide networks, and its inactivation can be a preventative measure that increases stress resilience.

Copyright ©2021 The Japanese Pharmacological Society

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