Increased excitation-inhibition balance and loss of GABAergic synapses in the serine racemase knockout model of NMDA receptor hypofunction
What are the neuronal mechanisms that are the neuronal mechanisms implicated in Schizophrenia? Why is the SRKO mouse such a great model? How does it compare to other models of Schizophrenia in general and NMDA hypofunction in particular? In this podcast Editor in Chief Professor Nino Ramirez and author, Dr. John Gray (University of California, Davis) discusses his manuscript titled “Increased excitation-inhibition balance and loss of GABAergic synapses in the serine racemase knockout model of NMDA receptor hypofunction”. Recently, disruption of E/I balance has become an area of considerable interest for psychiatric research. Here, we report a reduction in inhibition in the serine racemase KO mouse model of schizophrenia that increases E/I balance and enhances synaptically-driven neuronal excitability. This reduced inhibition was driven cell-autonomously in pyramidal cells lacking serine racemase, suggesting a novel mechanism for how chronic NMDA receptor hypofunction can disrupt information processing in schizophrenia. Listen to learn more about this fascinating study.
Shekib A. Jami, Scott Cameron, Jonathan M. Wong, Emily R. Daly , A.
Kimberley McAllister, and John A. Gray
Read the manuscript here: https://doi.org/10.1152/jn.00661.2020