Beta and Gamma Oscillations in Prefrontal Cortex During NMDA Hypofunction: An In Vitro Model of Schizophrenia Features. (15th July 2018)

• Record Type: Journal Article
• Authors: Rebollo, Beatriz; Perez-Zabalza, Maria; Ruiz-Mejias, Marcel; Perez-Mendez, Lorena; Sanchez-Vives, Maria V.
• Is Part Of: Neuroscience. Volume 383(2018)
• Page Start: 138
• Page End: 149
• Publication Date: 2018-07-15
• Subjects: CLZ clozapine -- CV coefficient of variation -- LFP local field potential -- MUA multiunit activity -- NMDAr N-methyl-d-aspartate receptor -- PCP phencyclidine -- PFC prefrontal cortex; NMDAr hypofunction -- slow oscillations -- beta frequency -- gamma frequency -- schizophrenia -- Up states; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.04.035
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: NMDAr blockers induce schizophrenia-like behavioral and electrophysiological features. We blocked NMDAr with MK-801 and studied spontaneous activity in prefrontal slices. MK-801 reduced slow oscillations and increased beta-gamma rhythms during Up states. Clozapine prevented the increase in beta-gamma oscillations during Up states. Some schizophrenia features can be reproduced in the local prefrontal circuit. Abstract: NMDA receptor (NMDAr) hypofunction has been widely used as a schizophrenia model. Decreased activation of NMDAr is associated with a disrupted excitation/inhibition balance in the prefrontal cortex and with alterations in gamma synchronization. Our aim was to investigate whether this phenomenon could be reproduced in the spontaneous oscillatory activity generated by the local prefrontal network in vitro and, if so, to explore the effects of antipsychotics on the resulting activity. Extracellular recordings were obtained from prefrontal cortex slices bathed in in vivo -like ACSF solution. Slow (<1 Hz) oscillations consisting of interspersed Up (active) and Down (silent) states spontaneously emerged. Fast-frequency oscillations (15–90 Hz) occurred during Up states. We explored the effects of the NMDAr antagonist MK-801 on the spontaneously generated activity. Bath-applied MK-801 induced a dose-dependent decrease in Up-state duration and in the frequency of Up states. However, the beta/gamma power during Up states significantly increased; this increase was in turn prevented by the antipsychotic drug clozapine. The increased beta/gamma power with NMDAr blockade implies that NMDAr activation in physiological conditions prevents hypersynchronization in this frequency range. High-frequency hypersynchronization following NMDAr blockade occurring in cortical slices suggests that—at least part of—the underlying mechanisms of this schizophrenia feature persist in the local cortical circuit, even in the absence of long-range cortical or subcortical inputs. The observed action of clozapine decreasing hypersynchronization in the local circuit may be one of the mechanisms of action of clozapine in preventing schizophrenia symptoms derived from NMDA hypofunction.