Mapping Functional Connectivity from the Dorsal Cortex to the Thalamus

Neural activity in the cortical-thalamic-cortical circuits are crucial for sensation, memory, decision and actions. Nevertheless, a systematic characterization of cortical-thalamic functional connectivity has not been achieved. Here, we developed a high throughput method in awake mice to systematically map functional connections from the dorsal cortex to the thalamus, by combing optogenetic-cortical-inhibition with single-neuron resolution thalamic recording. Photoinhibition of the cortex resulted in a rapid reduction of thalamic activity, revealing topographically-organized corticothalamic excitatory inputs. Cluster analysis showed that groups of neurons within individual thalamic nuclei exhibited distinct dynamics. Their cortical inputs expanded with time and the effects of photoinhibition were modulated by behavioral states. Furthermore, we found that individual thalamic neurons received convergent inputs from widespread cortical regions. Our results present a framework for collecting, analyzing, and presenting large electrophysiological datasets with region specific optogenetic perturbations and serve as a foundation for further investigation of information processing in the corticothalamic pathway.