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

描述(申请人提供：感觉表征由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图的特异性可以与丘脑皮质投射持平或超过，但人们对它们在知觉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(设计者受体，由设计者药物独占激活)，以解析来自听觉皮质初级和次级区域的第5层和第6层的皮质丘脑回路的功能贡献。通过在记录被动听声音或主动参与听任务的小鼠的丘脑神经元集合时使特定的皮质反馈电路沉默，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.