Complex opioid-driven modulation of glutamatergic and cholinergic neurotransmission in a GABAergic brain nucleus associated with emotion, reward, and addiction.

ABSTRACT: The medial habenula (mHb)/interpeduncular nucleus (IPN) circuitry is resident to divergent molecular, neurochemical, and cellular components which, in concert, perform computations to drive emotion, reward, and addiction behaviors. Although housing one of the most prominent mu-opioid receptor (mOR) expression levels in the brain, remarkably little is known as to how they impact mHb/IPN circuit function at the granular level. In this study, our systematic functional and pharmacogenetic analyses in mice demonstrate that mOR activation attenuates glutamatergic signaling while producing an opposing potentiation of glutamatergic/cholinergic co-transmission mediated by mHb substance P and cholinergic neurons, respectively. Intriguingly, this latter non-canonical augmentation is developmentally r

SUBMITTER: Chittajallu R 

PROVIDER: S-EPMC12668670 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature