Parvalbumin Interneurons Modulate Striatal Output and Enhance Performance during Associative Learning

The prevailing view is that striatal parvalbumin (PV)-positive interneurons primarily function to downregulate medium spiny projection neuron (MSN) activity via monosynaptic inhibitory signaling. Here, by combining in vivo neural recordings and optogenetics, we unexpectedly find that both suppressing and over-activating PV cells attenuates spontaneous MSN activity. To account for this, we find that, in addition to monosynaptic coupling, PV-MSN interactions are mediated by a competing disynaptic inhibitory circuit involving a variety of neuropeptide Y-expressing interneurons. Next we use optogenetic and chemogenetic approaches to show that dorsolateral striatal PV interneurons influence the initial expression of reward-conditioned responses but that their contribution to performance declines with experience. Consistent with this, we observe with large-scale recordings in behaving animals that the relative contribution of PV cells on MSN activity diminishes with training. Together, this work provides a possible mechanism by which PV interneurons modulate striatal output and selectively enhance performance early in learning. •Examined PV cell function with large-scale neural recordings and optogenetics•Suppressing or over-activating striatal PV cells reduces projection neuron firing•A disynaptic inhibitory circuit couples PV cells to projection neurons•The influence of PV cells on striatal output and behavior declines with experience Lee et al. show that striatal PV cells normally enhance striatal output but are capable of suppressing output, via competing inhibitory microcircuits. They show that the relative contribution of PV cells on striatal activity and behavioral performance diminishes with experience.