Synchronized oscillations caused by disinhibition in rodent neocortex are generated by recurrent synaptic activity mediated by AMPA receptors.
During disinhibition the neocortex generates synchronous activities. In neocortical slices application of GABA(A) and GABA(B) receptor antagonists transformed slow oscillations into large amplitude spike-wave discharges that contained a rhythmic ~10 Hz neocortical oscillation. The 10 Hz oscillations caused by disinhibition were highly region specific and were generated only in frontal agranular regions of neocortex, such as the primary motor cortex, but not in granular neocortex. Pharmacological manipulations showed that the 10 Hz oscillations were critically dependent on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. Current source density (CSD) analyses in slices using 16-site silicon probes revealed that the 10 Hz oscillations were expressed with large current sinks in the upper layers and smaller current sinks in the lower layers that precede them. The results indicate that blocking GABA(B) receptors in the agranular neocortex unmasks recurrent synaptic activity mediated by AMPA receptors that results in the generation of these oscillations.
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4. mcastro@bic.mni.mcgill.ca
Manuel A
MA
Castro-Alamancos
Pavlos
P
Rigas
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D019579:Neocortex / Q000502:physiology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D009991:Oscillometry; D018091:Receptors, AMPA / Q000502:physiology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000502:physiology*
D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C066430:CGP 35348; D001640:Bicuculline