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Coordinated Postnatal Maturation of Striatal Cholinergic Interneurons and Dopamine Release Dynamics in Mice.
McGuirt, Avery F; Post, Michael R; Pigulevskiy, Irena; Sulzer, David; Lieberman, Ori J.
Afiliação
  • McGuirt AF; Departments of Psychiatry, Neurology, Pharmacology, Columbia University Irving Medical Center, New York, New York 10032.
  • Post MR; Departments of Psychiatry, Neurology, Pharmacology, Columbia University Irving Medical Center, New York, New York 10032.
  • Pigulevskiy I; Departments of Psychiatry, Neurology, Pharmacology, Columbia University Irving Medical Center, New York, New York 10032.
  • Sulzer D; Departments of Psychiatry, Neurology, Pharmacology, Columbia University Irving Medical Center, New York, New York 10032 ojl2106@cumc.columbia.edu ds43@cumc.columbia.edu.
  • Lieberman OJ; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York 10032.
J Neurosci ; 41(16): 3597-3609, 2021 04 21.
Article em En | MEDLINE | ID: mdl-33664134
ABSTRACT
Dynamic changes in motor abilities and motivated behaviors occur during the juvenile and adolescent periods. The striatum is a subcortical nucleus critical to action selection, motor learning, and reward processing. Its tonically active cholinergic interneuron (ChI) is an integral regulator of the synaptic activity of other striatal neurons, as well as afferent axonal projections of midbrain dopamine (DA) neurons; however, little is known about its development. Here, we report that ChI spontaneous activity increases during postnatal development of male and female mice, concomitant with a decreased afterhyperpolarization (AHP). We characterized the postnatal development of four currents that contribute to the spontaneous firing rate of ChIs, including ISK, IA, Ih, and INaP We demonstrated that the developmental increase in INaP drives increased ChI firing rates during the postnatal period and can be reversed by the INaP inhibitor, ranolazine. We next addressed whether immature cholinergic signaling may lead to functional differences in DA release during the juvenile period. In the adult striatum, nicotinic acetylcholine receptors (nAChRs) prevent linear summation of DA release in response to trains of high-frequency stimuli. We show that, in contrast, during the second postnatal week, DA release linearly sums with trains of high-frequency stimuli. Consistently, nAChR antagonists exert little effect on dopamine release at postnatal day (P)10, but enhance the summation of evoked DA release in mice older than postnatal day P28. Together, these results reveal that postnatal maturation of ChI activity is due primarily to enhanced INaP and identify an interaction between developing cholinergic signaling and DA neurotransmission in the juvenile striatum.SIGNIFICANCE STATEMENT Motor skills and motivated behavior develop rapidly in juvenile rodents. Recent work has highlighted processes that contribute to the postnatal maturation of striatal principal neurons during development. The functional development of the striatal cholinergic interneuron (ChI), however, has been unexplored. In this study, we tracked the ontogeny of ChI activity and cellular morphology, as well as the developmental trajectory of specific conductances that contribute to the activity of these cells. We further report a link between cholinergic signaling and dopamine (DA) release, revealing a change in the frequency-dependence of DA release during the early postnatal period that is mediated by cholinergic signaling. This study provides evidence that striatal microcircuits are dynamic during the postnatal period and that they undergo coordinated maturation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sistema Nervoso Parassimpático / Envelhecimento / Dopamina / Neostriado / Neurônios Dopaminérgicos / Interneurônios Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sistema Nervoso Parassimpático / Envelhecimento / Dopamina / Neostriado / Neurônios Dopaminérgicos / Interneurônios Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article