BMI SEMINAR // Cerebral cortex interneuron myelination: Fundamental mechanisms and clinical implications

Previous studies have identified well-replicated structural abnormalities of white matter in schizophrenia, including in first-episode and treatment-naive patients. However, the causality of these changes has been difficult to ascertain.  Seemingly unrelated abnormalities of parvalbumin (PV) interneurons in schizophrenia post-mortem neocortex have also been consistently observed, the leading candidate mechanism for disease-related deficits in gamma oscillations.  In my talk, I will describe our findings combining family-based rare variant genetic discovery with induced pluripotent stem cell (iPSC) modeling which now suggest that oligodendrocyte progenitor cell dysfunction should be considered as a candidate etiological cell type in schizophrenia. Moreover, I will also discuss our discovery that fast-spiking PV interneurons in the neocortex and hippocampus are universally myelinated and exhibit a novel form of activity-dependent myelin plasticity, which could therefore represent an important locus of pathophysiological convergence.