Control of NMDA receptor-mediated activity by GABAergic mechanisms in mature and developing rat neocortex.
The effects of diazepam and low concentrations of bicuculline methiodide (BMI) on the expression of long-latency N-methyl-D-aspartate (NMDA) receptor-mediated activity was studied in supragranular layers of juvenile (14-18 days old) and adult rat (greater than or equal to 28 days) primary somatosensory cortex. In juvenile slices, orthodromic stimulation of layer VI/white matter evoked a long-lasting oscillatory field potential response which could be blocked by the NMDA receptor antagonist D(-)-2-amino-5-phosphonovaleric acid (D-APV) and by diazepam. Similar D-APV-sensitive responses could be observed in adult slices when the GABAergic system was slightly suppressed by adding low doses of BMI to the bathing solution. Our findings indicate that a small decrease in the efficacy of the inhibitory system, whether caused by developmental events or by processes that modulate inhibitory electrogenesis, can lead to NMDA receptor-mediated synchronized afterdischarges, which might play an important role in the functional maturation of the neocortex and in susceptibility to epileptogenesis.
Luhmann
H J
HJ
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305.
Prince
D A
DA
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013003:Somatosensory Cortex / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D005680:gamma-Aminobutyric Acid; D015763:2-Amino-5-phosphonovalerate; D003975:Diazepam; D001640:Bicuculline