A cholinergic medial septum input to medial habenula mediates generalization formation and extinction of visual aversion

• DOI: 10.1016/j.celrep.2022.110882
• Publication Date: 2022-05-31T15:00:47Z
• Authors: Ronghao Mu; Susu Tang; Xiaomeng Han; Hao Wang; Danhua Yuan; Jiajia Zhao; Yan Long; Hao Hong
• Keywords: 0301 basic medicine; Affect; Habenula; 03 medical and health sciences; Cholinergic Agents; Glutamic Acid; Cholinergic Neurons

Generalization of visual aversion is a critical function the brain that supports survival, but underlying neurobiological mechanisms are unclear. We establish rapid generalization procedure for inducing by dynamic stripe images. By using fiber photometry, apoptosis, chemogenetic and optogenetic techniques, behavioral tests, we find decreased cholinergic neurons' activity in medial septum (MS) leads to loss aversion. Strikingly, identify projection from MS neurons habenula (MHb) inhibition MS→MHb circuit disrupts aversion-generalization formation while its continuous activation subsequent extinction. Further studies show projections modulate possibly via M1 muscarinic acetylcholine receptors (mAChRs) downstream coreleasing glutamate acetylcholine. These findings reveal node extinction potentially provides insight into pathogenesis affective disorders.