Developmental regulation of thalamus-driven pauses in striatal cholinergic interneurons

Avery McGuirt; Irena Pigulevskiy; David Sulzer

doi:10.1016/j.isci.2022.105332

Developmental regulation of thalamus-driven pauses in striatal cholinergic interneurons

iScience. 2022 Oct 13;25(11):105332. doi: 10.1016/j.isci.2022.105332. eCollection 2022 Nov 18.

Authors

Avery McGuirt¹, Irena Pigulevskiy¹, David Sulzer¹

Affiliation

¹ Departments of Psychiatry, Neurology, Pharmacology, Columbia University Irving Medical Center, Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.

Abstract

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.

Keywords: Behavioral neuroscience; Biological sciences; Neuroscience.

Abstract

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