Associative Learning is Supported by State Dependent Changes to Inhibition in Striatal D1 and D2 Cells

Abstract

Auditory stimulus response associations are in part mediated by projections from the auditory cortex to the auditory striatum. Using chemogenetic techniques in freely moving Mongolian gerbils, we show that suppression of glutamatergic input from auditory cortex layer 5 to the auditory striatum impacts both learning speed and performance in a sound discrimination task. Early cortical suppression during learning caused significant delays in task acquisition, while suppression after task acquisition affected discrimination performance. Whole-cell recordings sampled throughout learning revealed a transient reduction in postsynaptic inhibition in both striatal D1 and D2 cells. In contrast, when baseline striatal inhibitory strengths were reduced by a transient sensory deprivation, learning was associated with briefly augmented inhibition and evoked firing rates. The latter was supported by phenotype-dependent compensatory mechanisms in striatal D1 and D2 cell intrinsic membrane properties. Together, these results reveal a flexible corticostriatal inhibitory synaptic plasticity mechanism that accompanies associative auditory learning.