SCSB Lunch Series with Dr. Haoran Xu and Dr. Beizhen Zhang – Investigating Neural Circuit Abnormalities in SHANK3 Mutant Marmosets
December 5 | 12:00 pm - 1:00 pm
Date: Friday, December 5, 2025
Time: 12:00pm – 1:00pm
Location: Simons Center Conference room 46-6011 + Zoom [https://mit.zoom.us/j/95992863075]
Speakers: Haoran Xu, Ph.D., Research Scientist & Beizhen Zhang, Ph.D., Postdoctoral Fellow
Affiliation: Desimone Lab, McGovern Institute, MIT
Talk title: Investigating Neural Circuit Abnormalities in SHANK3 Mutant Marmosets
Abstract: Phelan-McDermid Syndrome (PMS) is a neurodevelopmental disorder caused by mutations or deletions in the SHANK3 gene, a key component for maintaining synaptic structure and neural circuit integrity. Individuals with PMS exhibit profound social communication deficits, intellectual disability, and sensory abnormalities, yet the neural circuit mechanisms underlying these symptoms remain elusive. In this talk, I will present our ongoing work using SHANK3 mutant marmosets as a primate model to probe these circuit dysfunctions. We implanted four 64-channel ECoG arrays across temporal and prefrontal regions in mutant and wild-type animals and examined their neural dynamics during social perception, cognitive, and auditory tasks. Despite showing normal gaze patterns while viewing faces or movies, SHANK3 mutants exhibited reduced high-gamma activity in face-selective regions and weakened social representations in both the prefrontal (PFC) and inferotemporal (IT) cortices. During working memory tasks, mutants performed more poorly, with their deficits linked to elevated alpha and high-gamma power in the PFC during the delay period. In the auditory domain, they showed hypoactivity in auditory cortical areas but paradoxical hyper-responsivity to noise-like sounds in the PFC and visual regions, suggesting impaired inhibition. Together, these findings reveal how SHANK3 disruption alters distributed neural circuits underlying social, cognitive, and sensory processing, offering a window into the circuit-level basis of PMS and related neurodevelopmental disorders.