McGuirt Avery, Pigulevskiy Irena, Sulzer David
Departments of Psychiatry, Neurology, Pharmacology, Columbia University Irving Medical Center, Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
iScience. 2022 Oct 13;25(11):105332. doi: 10.1016/j.isci.2022.105332. eCollection 2022 Nov 18.
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 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 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.
为响应显著的感觉线索，紧张性活动的纹状体胆碱能中间神经元（ChI）表现出一种典型的同步“暂停”，据认为这有助于学习和动机行为的执行。我们报告，在幼年（P10）小鼠的脑片中，丘脑纹状体驱动的ChI暂停增强，而在青春期前（P28）和成年（P100）小鼠中表达降低，同时ChIs的兴奋性输入减弱。我们的数据与先前的报道一致，即成年ChI暂停依赖于多巴胺信号传导，但我们发现P10时强烈的暂停是多巴胺非依赖性的。相反，非失活性延迟整流Kv7.2/3电流的表达升高促进了幼年ChIs的暂停。由于这种电流在发育过程中减少，I的平行增加进一步减弱了暂停表达。这些发现表明，ChI暂停表达的细胞内在和回路机制是由发育决定的，并且可能是神经系统成熟时学习特性变化的基础。
