Acute NMDA receptor antagonism disrupts synchronization of action potential firing in rat prefrontal cortex.
Antagonists of N-methyl-D-aspartate receptors (NMDAR) have psychotomimetic effects in humans and are used to model schizophrenia in animals. We used high-density electrophysiological recordings to assess the effects of acute systemic injection of an NMDAR antagonist (MK-801) on ensemble neural processing in the medial prefrontal cortex of freely moving rats. Although MK-801 increased neuron firing rates and the amplitude of gamma-frequency oscillations in field potentials, the synchronization of action potential firing decreased and spike trains became more Poisson-like. This disorganization of action potential firing following MK-801 administration is consistent with changes in simulated cortical networks as the functional connections among pyramidal neurons become less clustered. Such loss of functional heterogeneity of the cortical microcircuit may disrupt information processing dependent on spike timing or the activation of discrete cortical neural ensembles, and thereby contribute to hallucinations and other features of psychosis induced by NMDAR antagonists.
Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada.
Leonardo A
LA
Molina
Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada.
Ivan
I
Skelin
Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada.
Aaron J
AJ
Gruber
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004566:Electrodes; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate