Origin of Synchronized Oscillations Induced by Neocortical DisinhibitionIn Vivo

Abstract

During disinhibition, the neocortex generates synchronous activities. Block of GABA(A) receptors in neocortex transforms cortical slow-wave oscillations into large-amplitude approximately 1 Hz discharges consisting of a negative spike or multiple negative spikes riding on a positive wave. Further block of GABA(B) receptors in neocortex slows the discharges to approximately 0.5 Hz and increments the number of negative spikes forming rhythmic approximately 10 Hz neocortical oscillations. Although the thalamus responds robustly to these neocortical discharges, these are unaffected by thalamic inactivation using tetrodotoxin. Thus, an important problem relates to the origin of these activities within the neocortex. Current source density analysis and intracellular recordings revealed that the first negative spike in a discharge corresponded to a current sink that reflected a paroxysmal depolarizing shift (PDS) and could originate in the lower layers or in the upper layers. Regardless of the origin (upper or lower layer), the initial current sink always spreads to the same site in upper layer V-IV. In contrast, the approximately 10 Hz oscillation that follows the initial negative spike corresponds to current sinks that always originate in the lower layers but do not spread to upper layer V-IV, jumping directly to the upper layers. Each current sink in the approximately 10 Hz oscillation reflects a small PDS and is followed by a current source that reflects the repolarization after each PDS.