This study shows that SCN2A deficiency in human brain assembloids disrupts cortico-striatal circuitry by impairing axonal projections and synaptic transmission, leading to hyperexcitability.

Neuron · Sep 1, 2026Peer-reviewedNeuroscience

Epilepsy-Associated SCN2A-L1342P Mutation Drives Network Hyperexcitability and Widespread Transcriptomic Changes in Human Cortical Organoids

Maria I. Olivero-Acosta, Morgan J. Robinson, Zhefu Que, Zaiyang Zhang, Karen V. Salazar‐Salazar, Hope Elizabeth Harlow, Vinayak Shankar, Seoyeon Hong, Muhan Wang, C. Max Otterbacher, Hina Kadono, Manasi Suchit Halurkar, Harish Kothandaraman, Nadia A. Lanman, Trang Nguyen, , Yang Yang

This study investigates the effects of the SCN2A-L1342P mutation in human cortical organoids, finding increased neuronal excitability, enhanced synaptic transmission, and transcriptomic changes related to synaptic and developmental pathways.

Epilepsia · Jul 30, 2026Peer-reviewedNeuroscience

Chemogenetic Inhibition of the Cortical Amygdala Reduces Alcohol Intake and Restores Thalamic Connectivity in Dependent Female Mice

Tiange Xiao, Xi Cheng, Jingliang Zhang, Yueyi Chen, Zhefu Que, Xiaoling Chen, Danielle McAuliffe, Alyssa Boisvert, Yang Yang, Alexander A. Chubykin, Adam Kimbrough

This study shows that inhibiting the cortical amygdala reduces alcohol intake in dependent mice and restores thalamic connectivity during withdrawal.

bioRxiv · May 12, 2026 · PreprintNeuroscience

Human microglia in brain assembloids display region-specific diversity and respond to hyperexcitable neurons carrying SCN2A mutation

Jiaxiang Wu, Xiaoling Chen, Jingliang Zhang, Kyle W. Wettschurack, Morgan J. Robinson, Weihao Li, Yuanrui Zhao, Ye-Eun Yoo, Brody A. Deming, Akila D. Abeyaratna, Zhefu Que, Dongshu Du, Matthew Tegtmeyer, Chongli Yuan, William C. Skarnes, , Yang Yang

This study uses brain organoids and assembloids with microglia to show region-specific microglial diversity and their response to SCN2A mutation-induced neuronal hyperactivity.

bioRxiv · Jun 4, 2025 · PreprintNeuroscience

Restoration of excitation/inhibition balance enhances neuronal signal-to-noise ratio and rescues social deficits in autism-associated Scn2a-deficiency

Jingliang Zhang, Muriel Eaton, Xiaoling Chen, Yuanrui Zhao, Shivam Kant, Brody A. Deming, Kothandaraman Harish, Huynhvi P. Nguyen, Yue Long Shu, Shirong Lai, Jiaxiang Wu, Zhefu Que, Kyle W. Wettschurack, Zaiyang Zhang, Tiange Xiao, , Yang Yang

This study shows that restoring NaV1.2 expression in adulthood rescues social deficits and improves neuronal signal-to-noise ratio in Scn2a-deficient mice.

bioRxiv · Mar 4, 2025 · PreprintNeuroscience

Human iPSC-derived microglia sense and dampen hyperexcitability of cortical neurons carrying the epilepsy-associated SCN2A-L1342P mutation

Zhefu Que, Maria I. Olivero-Acosta, Morgan J. Robinson, Ian Chen, Jingliang Zhang, Kyle W. Wettschurack, Jiaxiang Wu, Tiange Xiao, C. Max Otterbacher, Vinayak Shankar, Hope Elizabeth Harlow, Seoyong Hong, Benjamin Zirkle, Muhan Wang, Ningren Cui, , Yang Yang

This study shows human iPSC-derived microglia detect and reduce hyperexcitability in neurons with the SCN2A-L1342P epilepsy mutation through morphological and calcium changes and reduced sodium channel current density.

Journal of Neuroscience · Nov 18, 2024Peer-reviewedNeuroscience

Severe deficiency of voltage-gated sodium channel NaV1.2 elevates neuronal excitability in adult mice

Jingliang Zhang, Xiaoling Chen, Muriel Eaton, Jiaxiang Wu, Zhixiong Ma, Shirong Lai, Anthony Park, Talha S. Ahmad, Zhefu Que, Ji Hea Lee, Tiange Xiao, Yuansong Li, Yujia Wang, Maria I. Olivero-Acosta, James A. Schaber, , Yang Yang

This study shows that severe NaV1.2 deficiency increases neuronal excitability in adult mice, challenging the current understanding of its role in autism and epilepsy.

Cell Reports · Aug 1, 2021Peer-reviewedNeuroscience

Sodium channel Nav1.2-L1342P variant displaying complex biophysical properties renders hyperexcitability of cortical neurons derived fromhuman iPSCs

Zhefu Que, Maria I. Olivero-Acosta, Jingliang Zhang, Muriel Eaton, William C. Skarnes, Yang Yang

This study investigates the effects of the SCN2A L1342P variant in human iPSC-derived neurons, showing increased excitability and resistance to phenytoin, but responsiveness to PTx3.

bioRxiv · Jan 18, 2021 · PreprintNeuroscience