Kavli Affiliate: Samuel Pleasure
| Authors: Jing Zhou, Ariele Greenfield, Rita Loudermilk, Christopher Bartley, Baouyen Tran, Chao Zhao, Hong Wang, Michael Wilson and Samuel Pleasure
| Summary:
Abstract NMDA receptor autoimmune encephalitis (NMDAR-AE) is characterized by cerebrospinal fluid (CSF)-resident anti-NMDA receptor autoantibodies that cause behavioral and neurologic deficits. Although many symptoms are responsive to immunotherapy, for many patients functionally impairing deficits persist. We used patient-derived GluN1 and GluN2A-specific monoclonal antibodies (mAbs) to interrogate the molecular and circuit basis for persistent sensory-motor deficits following NMDAR-AE. During postnatal development, intracortical injection of either mAb disrupted callosal circuit formation with excess callosal projections in primary somatosensory cortex (S1), although the anti-GluN1 antibody provoked the more severe phenotype. S1 circuit disruption during development results in permanent axon morphology alterations and sensory-motor deficits lasting to adulthood. The severity of sensory-motor deficits was correlated with the severity of axon morphology alterations, and these anatomic changes are associated with sensory-motor behavior deficits similar to those in children NMDAR-AE. Our studies provide a molecular, cellular, and circuit basis for persistent neuropsychiatric deficits in NMDAR-AE. Competing Interest Statement The authors have declared no competing interest.