Impairment of Neural Coordination in Hippocampal Neuronal Ensembles After a Psychotomimetic Dose of Dizocilpine

Ewa Szczurowska, Nikhil Ahuja, Přemysl Jiruška, Eduard Kelemen, Aleš Stuchlík

Prog Neuropsychopharmacol Biol Psychiatry. 2018 Feb 2;81:275-283.

PMID: 28935586

Abstract:

The discoordination hypothesis of schizophrenia posits discoordination of neural activity as the central mechanism that underlies some psychotic symptoms (including 'hallmark' cognitive symptoms) of schizophrenia. To test this proposition, we studied the activity of hippocampal neurons in urethane anesthetized Long Evans rats after 0.15mg/kg dizocilpine (MK-801), an N-Methyl-d-aspartate (NMDA) glutamate receptor antagonist, which can cause psychotic symptoms in humans and cognitive control impairments in animals. We observed that MK-801 altered the temporal coordination, but not rate, of neuronal firing. Coactivation between neurons increased, driven primarily by increased coincident firing of cell pairs that did not originally fire together before MK-801 injection. Increased pairwise coactivation manifested as disorganized discharge on the level of neuronal ensembles, which in turn could lead to disorganization in information processing. Disorganization of neuronal activity after a psychotomimetic dose of MK-801 supports the discoordination hypothesis of psychosis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP77086227-A	(+)-MK 801 Maleate - CAS 77086-22-7		77086-22-7	Price