Horizontal spread of synchronized activity in neocortex and its control by GABA-mediated inhibition

Y. Chagnac-Amitai, B. W. Connors

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411 Scopus citations


Suppression of GABA(A) receptor-mediated inhibition disrupts the neural activity of neocortex and can lead to synchronized discharges that mimic those of partial epilepsy. We have studied the role of GABA(A)-mediated inhibition in controlling the synchronization and horizontal (tangential) spread of cortical activity. Slices of rat SmI were maintained in vitro and focally stimulated in layer VI while recording with a horizontal array of extracellular electrodes. Inhibition was slightly suppressed by adding low concentrations of the GABA(A) antagonists bicuculline or bicuculline methiodide to the bathing medium. Under control conditions neural activity was narrowly confined to a vertical strip of cortex. The horizontal spread of activity expanded about twofold in the presence of antagonist concentrations (≤ 0.5 μM) that were expected to suppress GABA(A) function by no more than 10-20%. At antagonist concentrations between 0.4 and 1.0 μM, evoked epileptiform activity appeared. These threshold-dose epileptiform events showed wide variations in size and duration (even at the same recording site), very variable distances of horizontal propagation, specific sites of propagation failure, reversals of propagation direction, and directional asymmetries in their probability of propagation. This contrasts with activity observed previously (Ref. 9) in high bicuculline concentrations (≥ 10 μM): large, stereotyped events that propagate reliably without decrement or reflection. Intracellular recordings were obtained from pyramidal neurons in layers II/III in the presence of ≤ 1 μM bicuculline. Inhibitory postsynaptic potentials (IPSPs) were observed during both primary evoked responses and propagating epileptiform events and were often comparable in size and duration to those in untreated cortex. Epileptiform field potentials were always correlated with synaptic activity in single cells, but the pattern and type of PSPs varied with the form of the field potentials. Large amplitude epileptiform events coincided with an overwhelming inhibition of upper layer neurons. We conclude that 1) the horizontal spread of normal cortical activity is strongly constrained by GABA(A)-mediated IPSPs, 2) a relatively small reduction in the efficacy of inhibition leads to a large increase in the spread of excitation, 3) initiation and propagation of synchronized epileptiform activity can occur even in the presence of robust cortical inhibition, and 4) the character of epileptiform activity is strongly affected by the influences of inhibition.

Original languageEnglish
Pages (from-to)747-758
Number of pages12
JournalJournal of Neurophysiology
Issue number4
StatePublished - 1 Jan 1989
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience
  • Physiology


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