Increased excitation-inhibition balance and loss of GABAergic synapses in the serine racemase knockout model of NMDA receptor hypofunction
Shekib A. Jami, Scott Cameron, Jonathan M. Wong, Emily R. Daly, A. Kimberley McAllister, J.A. Gray
Abstract
Recently, disruption of excitation/inhibition (E/I) balance has become an area of considerable interest for psychiatric research. Here, we report a reduction in inhibition in the serine racemase knockout 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.
Topics & Concepts
NeuroscienceGABAergicNMDA receptorSynapseInhibitory postsynaptic potentialNeurochemicalGlutamatergicKnockout mousePyramidal cellChemistryNeurotransmissionReceptorBiologyGlutamate receptorHippocampusBiochemistryAmino Acid Enzymes and MetabolismNeuroscience and Neuropharmacology ResearchTryptophan and brain disorders