NMDA receptor-mediated transmission contributes to network 'hyperexcitability' in the rat insular cortex.
The insular cortex (IC) plays distinct roles under physiological and pathological conditions. However, the mechanisms regulating excitability in this area remain unknown. By employing field potential and sharp-electrode intracellular recordings in horizontal rat brain slices comprising the IC and the perirhinal cortex, we studied here the intrinsic and network characteristics of neurons in the agranular IC. These cells generated regular action potential firing with weak adaptation during intracellular injection of depolarizing current pulses, and were pyramidal in shape when neurobiotin filled. Spontaneous, field events (duration = 2.3 +/- 0.25 s; intervals of occurrence = 44.9 +/- 6.3 s) were identified in 22/52 slices and corresponded in IC neurons to intracellular depolarizations with action potential firing. Similar field and intracellular discharges were elicited in all slices by electrical stimuli. Antagonizing N-methyl-d-aspartate (NMDA) receptors blocked the spontaneous activity and reduced or abolished the stimulus-induced discharges. In the latter cases, stimuli elicited depolarizing events that became hyperpolarizing at about -64 mV, suggesting the contribution of gamma-aminobutyric acid (GABA)(A) receptor-mediated conductances. Our findings identify for the first time some functional properties of agranular IC neurons and point at a powerful NMDA receptor-mediated mechanism implementing network hyperexcitability. This feature may contribute to the role of IC in neurological disorders.
Inaba
Yuji
Y
Montreal Neurological Institute and Departments of Neurology & Neurosurgery, and of Physiology, McGill University, Montréal, QC, Canada H3A 2B4.
de Guzman
Philip
P
Avoli
Massimo
M
D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010721:Phosphinic Acids / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D016194:Receptors, N-Methyl-D-Aspartate; C085075:CGP 55845A