2026 Theses Doctoral

Inferring recurrent cortical circuit motifs and mechanisms from holographic optogenetic perturbations

Chau, Ho Yin

The cerebral cortex is strongly recurrently connected with complex wiring rules. What are these wiring rules, and how do they coordinate to perform useful computations? A promising approach is to experimentally measure cortical responses to causal perturbations of neural activity, then infer the recurrent circuit motifs and mechanisms that generate these perturbation responses.

In particular, by enabling perturbations at single-cell resolution, holographic optogenetics may unveil recurrent circuit mechanisms at a greater level of detail than can be achieved with other perturbation techniques. However, we currently lack a general theory of perturbation responses in recurrent circuits, limiting our ability to infer the cortical circuitry that produces these responses. My thesis addresses this issue in two parts.

First, I derive an exact analytical solution of perturbation responses in a linear recurrent cortical model, and use it to infer recurrent cortical circuit motifs from single-cell perturbation data. Next, I develop a theory of perturbation responses in nonlinear recurrent networks, and apply it to holographic optogenetics data to reveal an SST-mediated nonlinear recurrent circuit mechanism underlying tuned ensemble perturbations. Together, these results establish a theoretical foundation of holographic perturbation responses and provide new insights into recurrent cortical circuits.