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

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 chloride transporter 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 synchronization between individual GABA neurons and increased dopamine responses to rewards and reward-related stimuli. Conversely, enhancing KCC2 function during learning reduced GABA synchronization, diminished relevant dopa..., , # Data from: Dynamic changes in chloride homeostasis coordinate midbrain inhibitory network activity during reward learning

Dataset DOI: [10.5061/dryad.44j0zpcv7](https://doi.org/10.5061/dryad.44j0zpcv7)

## Description of the data and file structure

We utilized multidisciplinary approach in transgenic rats to demonstrate that midbrain GABA neurons exhibit altered ionic homeostasis through functional downregulation of the potassium chloride cotransporter, KCC2, within fine temporal windows during reward learning. Specifically using rat Pavlovian learning tests, slice patch clamp recordings, and immunostaining, we show that during the acquisition phase of learning, KCC2 undergoes transient downregulation, manifesting as altered inhibitory synaptic transmission in VTA GABA neurons (Figures 1 and 2). Using a variety of physiological methods, we show that KCC2 alterations were associated with increased firing synchrony within midbrain GABA neuronal networks and enhanced phasic bursting in...,