BME PhD Dissertation Defense: Songyang Wang

Title: "Structural and functional organization of somatosensory cortex microcircuits in working-memory-related processing"

Advisory Committee: Jerry L. Chen, Ph.D. – Biology, BME (Research Advisor) Kamal Sen, Ph.D.- BME (Chair) Michael N. Economo, Ph.D.- BME Wei-Chung Allen Lee, Ph.D.– Harvard Medical School Neurology and Neurobiology Gabriel Koch Ocker, Ph.D – Mathematics and Statistics

Abstract: Working memory-related activity in the sensory cortex has been increasingly recognized, and previous work has shown context-dependent delay-period signals in the mouse somatosensory cortex during a delayed non-match-to-sample task. However, the synaptic circuit organization underlying these signals remains unresolved. To address this gap, we combined in vivo two-photon calcium imaging with synaptic-resolution electron microscopy to analyze the structural and functional organization of local microcircuits in primary and secondary somatosensory cortex across cortical layers and areas. The results showed that neurons tuned to different sensory stimuli were more spatially segregated, whereas higher-order task-related working-memory signals were more spatially intermixed and embedded within sensory-structured local subnetworks. Synaptic connectivity was strongly shaped by cell type, spatial distance, subnetwork structure, and functional identity. In addition, the circuit exhibited like-to-like excitatory connectivity together with recurrent or mutual inhibitory structure. Collectively, these findings indicate that local architecture in S1 and S2 constrains how working-memory-related processing can be implemented in the sensory cortex. This work narrows the range of plausible microcircuit models and provides an empirical basis for future mechanistic and computational testing.