The role of glutamatergic inputs onto parvalbumin-positive interneurons: relevance for schizophrenia.
Cognitive impairment, a core feature of schizophrenia, has been suggested to arise from a disturbance of gamma oscillations that is due to decreased neurotransmission from the parvalbumin (PV) subtype of interneurons. Indeed, PV interneurons have uniquely fast membrane and synaptic properties that are crucially important for network functions such as feedforward inhibition or gamma oscillations. The causes leading to impairment of PV neurotransmission in schizophrenia are still under investigation. Interestingly, NMDA receptors (NMDARs) antagonism results in schizophrenia-like symptoms in healthy adults. Additionally, systemic NMDAR antagonist administration increases prefrontal cortex pyramidal cell firing, apparently by producing disinhibition, and repeated exposure to NMDA antagonists leads to changes in the GABAergic markers that mimic the impairments found in schizophrenia. Based on these findings, PV neuron deficits in schizophrenia have been proposed to be secondary to (NMDAR) hypofunction at glutamatergic synapses onto these cells. However, NMDARs generate long-lasting postsynaptic currents that result in prolonged depolarization of the postsynaptic cells, a property inconsistent with the role of PV cells in network dynamics. Here, we review evidence leading to the conclusion that cortical disinhibition and GABAergic impairment produced by NMDAR antagonists are unlikely to be mediated via NMDARs at glutamatergic synapses onto mature cortical PV neurons.
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam 1081 HV, The Netherlands.
Diana C
DC
Rotaru
David A
DA
Lewis
Guillermo
G
Gonzalez-Burgos
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000473:pathology*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007395:Interneurons / Q000378:metabolism*; D009434:Neural Pathways; D010320:Parvalbumins / Q000378:metabolism*
D010320:Parvalbumins; D018698:Glutamic Acid