Developmental regulation of thalamus-driven pauses in striatal cholinergic interneurons

In response to salient sensory cues, the tonically active striatal cholinergic interneuron (ChI) exhibits a characteristic synchronized pause thought to facilitate learning and the execution of motivated behavior. We report that thalamostriatal-driven ChI pauses are enhanced in ex vivo brain slices from infantile (P10) mice, with decreasing expression in preadolescent (P28) and adult (P100) mice concurrent with waning excitatory input to ChIs. Our data are consistent with previous reports that the adult ChI pause is dependent on dopamine signaling, but we find that the robust pausing at P10 is dopamine independent. Instead, elevated expression of the noninactivating delayed rectifier Kv7.2/3 current promotes pausing in infantile ChIs. Because this current decreases over development, a parallel increase in I-h further attenuates pause expression. These findings demonstrate that cell intrinsic and circuit mechanisms of ChI pause expression are developmentally determined and may underlie changes in learning properties as the nervous system matures.

Automated summary

In this study, the enhanced pause expression of striatal cholinergic interneurons (ChI) in infantile mice is found to decrease as the excitatory input declines during development. The activation of noninactivating delayed rectifier Kv7.2/3 current in infantile ChIs promotes pause expression, which decreases over development, accompanied by an increase in I-h, demonstrating that the developmental changes in intrinsic and circuit mechanisms of ChI pause expression may underlie alterations in learning properties as the nervous system matures.