Dynamic changes in chloride homeostasis coordinate midbrain inhibitory network activity during reward learning.

ABSTRACT: The ability to associate environmental stimuli with positive outcomes is a fundamental form of learning. While extensive research has focused on midbrain dopamine neurons during associative learning, less is known about learning-mediated changes in the afferents that shape dopamine neuron responses. We demonstrate in rats that during critical phases of learning, anion homeostasis in midbrain inhibitory GABA neurons - a primary source of input to dopamine neurons - is disrupted due to downregulation of the potassium chloride cotransporter KCC2. This alteration in GABA neurons preferentially impacted lateral mesoaccumbal dopamine pathways and was not observed after learning was established. At the network level, learning-mediated KCC2 downregulation was associated with enhanced synchronizati

SUBMITTER: Woo J 

PROVIDER: S-EPMC12689616 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature