Data from: 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 dopamine
signaling, and prevented cue-reward associations. Thus, circuit-specific
adaptations in midbrain GABA neurons are crucial for forming new
reward-related behaviors.