Somatostatin interneurons select dorsomedial striatal representations of the initial motor learning phase

The dorsomedial striatum (DMS) is an associative node involved in the initial formation of motor sequences and the adaptation of ongoing actions. During early associative or motor learning tasks, DMS shows a global reduction of activity, eventually refining a subset of active neurons whose number correlates with animal performance. Understanding how this representation emerges is crucial to deciphering the plasticity mechanisms underlying early phases of learning. Here, we propose that local inhibitory interneurons shape early DMS representation and influence task performance. We report that the selective manipulation of somatostatin (SOM)-positive interneurons disrupts DMS activity reorganization and modulates early-learning performance. This effect is cell specific, as manipulation of parvalbumin-positive interneurons has no effect. We also identify the high plasticity of SOM-mediated feedforward inhibition as a critical modulator of striatal projection neuron firing activity. Hence, SOM interneurons are key DMS circuit organizers and set the pace of early learning.