A network model of the modulation of gamma oscillations by NMDA receptors in cerebral cortex
Destexhe, A., Susin, E.
This preprint (2021) used computational models of cortical networks generating gamma oscillations (frequency of brainwaves) while integrating the actions of NMDA-receptor drugs like ketamine to better understand the mechanism by which these drugs produce gamma oscillations as seen in disorders like schizophrenia. It was found that ketamine (like substances) induce an increased excitability state and increase the response to external inputs which may help to explain phenomena like hallucinations.
Abstract
Psychotic drugs such as ketamine induce symptoms close to schizophrenia, and stimulate the production of gamma oscillations, as also seen in patients, but the underlying mechanisms are still unclear. Here, we have used computational models of cortical networks generating gamma oscillations, and have integrated the action of drugs such as ketamine to partially block n-methyl-d-aspartate (NMDA) receptors. The model can reproduce the modulation of gamma oscillations by NMDA-receptor antagonists, assuming that antagonists affect NMDA receptors predominantly on inhibitory interneurons. We next used the model to compare the responsiveness of the network to external stimuli, and found that when NMDA channels are blocked an increase of Gamma power is observed altogether with an increase of network responsiveness. However, this responsiveness increase applies not only to gamma states but also to asynchronous states with no apparent gamma. We conclude that NMDA antagonists induce increased excitability state, which may or may not produce gamma oscillations, but the response to external inputs is exacerbated, which may explain phenomena such as altered perception or hallucinations.