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

描述（由申请人提供）：感觉表征通过连接大脑皮层和丘脑的上行和下行连接动态维持。虽然皮质丘脑下行投射的整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的方法称为DREADDs（设计师受体专门激活的设计师药物）解析的皮质丘脑电路，从第5层与第6层的初级和次级区域的听觉皮层的功能贡献。通过沉默特定的皮层反馈回路，同时记录被动听声音或积极参与听任务的小鼠丘脑神经元的集合，我们将更深入地了解多个并行反馈系统的工作原理，这些反馈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.