A chemical-genetic approach to decipher the function of corticothalamic feedback

描述（由申请人提供）：感觉表征是通过连接大脑皮层和丘脑的上升和下降连接动态维持的。虽然下行皮质丘脑投射的总体范围和地形特异性可以等于或超过丘脑皮质投射，但对它们在感知或学习中的作用知之甚少。在这里，我们提出了一种新的化学遗传学方法，称为DREADDs（由设计药物独家激活的设计受体），以分析听觉皮层主要和次要区域的第5层与第6层产生的皮质丘脑回路的功能贡献。通过沉默特定的皮质反馈回路，同时记录被动聆听声音或积极参与聆听任务的小鼠丘脑神经元群，我们将更深入地了解多个并行反馈系统的工作原理，这些系统使大脑皮层能够修改其传入输入流。

DESCRIPTION (provided by applicant: Sensory representations are dynamically maintained by ascending and descending connections linking the cerebral cortex and the thalamus. Although the overall extent and topographic specificity of descending corticothalamic projections can equal or surpass that of thalamocortical projections, little is known about their role in perception or learning. Here, we propose a new chemical-genetic approach known as DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) to parse the functional contribution of corticothalamic circuits that arise from layer 5 versus layer 6 of primay and secondary areas of the auditory cortex. By silencing specific cortical feedback circuits while recording from ensembles of thalamic neurons in mice that are either passively listening to sound or are actively engaged in listening tasks, we will gain deeper insight into the workings of multiple, parallel feedback systems that enable the cerebral cortex to modify its afferent input stream.