NMDA-induced changes in a cortical network in vivo are prevented by AMPA.
Analogues of glutamic acid including N-methyl-D-aspartic acid (NMDA) depolarise neurones of the cerebral cortex in vivo and thus change the size of the somatosensory evoked potentials (SEPs). The potentials recover rapidly despite maintained superfusion with NMDA, suggesting a form of neuronal desensitisation or network adaptation. In this study potentials were evoked at the cortical surface by electrical stimulation of the contralateral forepaw and compounds applied topically to the cortical surface by a cortical cup. NMDA at 50-250 microM caused a concentration-dependent decrease in the amplitude of the SEPs, with the highest concentration always abolishing them. AMPA at 50 microM did not affect evoked potentials when applied alone, but prevented the NMDA. Such AMPA-NMDA interactions were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and enhanced by cyclothiazide (which prevents AMPA desensitisation). Superfusion with potassium did not change sensitivity to NMDA. These results suggest that, in the rat cerebral cortex in vivo, activation of AMPA receptors can induce a loss of the network response to activation of NMDA receptors. Such a phenomenon may have physiological and therapeutic implications.
Addae
J I
JI
Department of Preclinical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago. addae@carib-link.net
Evans
S M
SM
Ali
N
N
Stone
T W
TW
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001581:Benzothiadiazines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects* / Q000502:physiology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001581:Benzothiadiazines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C004639:cyclothiazide; D011188:Potassium