Causal investigation of Cortical Communication

This project will reveal the causal rules that govern activity transmission across layers of the cerebral cortex by leveraging unique photonic probes that can read and write neural activity with high resolution. The evolutionary expansion of a common cortical circuit to perform diverse functions demonstrates this circuit’s computational power, yet we do not know the basic communication rules that drive this versatile computational system. Due to a lack of causal experiments, we do not know how activity in one cortical layer activates the other layers. Nor do we understand how long-range projections propagate activity to downstream regions. Finally, we do not understand how behavioral state modifies these interlaminar and long-range communication rules. We can now answer these questions due to advances in precision optogenetics and new Neuropixels Opto probes developed by the host laboratory, which combine electrophysiological recording with optogenetic activation for causal interrogation of circuit dynamics. First, I will causally test how activity is transmitted across cortical layers, by using targeted layer-specific activation to reveal whether activity flows through feedforward canonical or parallelized non-canonical communication pathways (Objective 1). Second, I will reveal the causal layer-specific rules of long-range communication across cortical areas, by testing the layer-specific impacts of activating long-range projections from superficial vs deep layers (Objective 2). Finally, I will quantify state-dependent changes in local and long-range communication rules, by pairing targeted activation, local and downstream recording, and monitoring of locomotor and arousal state (Objective 3). By pairing these causal perturbations with robust computational analysis, we will gain a fundamental understanding of the communication rules that give cortical circuits their remarkable computational power.