Muscarinic depression of synaptic transmission in the epileptogenic GABA withdrawal syndrome focus

C. Silva-Barrat, M. Szente, Ch Menini, J. C. Velluti, J. Champagnat

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Abstract

The GABA withdrawal syndrome (GWS) is a model of local status epilepticus consecutive to the interruption of a prolonged GABA infusion into the rat somatomotor cortex. Bursting patterns in slices from GWS rats include intrinsic bursts of action potentials (APs) induced by intracellular depolarizing current injection and/or paroxysmal depolarization shifts (PDSs) induced by white matter stimulation. Possible changes in the effects of cholinergic drugs after in vivo induction of GWS were investigated on bursting cells (n = 30) intracellularly recorded in neocortical slices. In GWS slices, acetylcholine (Ach, 200-1000 μM) or carbachol (Cch, 50 μM) applications increased the number of bursts induced by depolarizing current injection while synaptically induced PDSs were significantly diminished (by 50-60%) or even blocked independently of the cholinergic-induced depolarization, The intrinsic burst facilitation and PDS depression provoked by Ach or Cch were mimicked by methylacetylcholine (mAch, 100-400 μM, n = 11), were reversed by atropine application (1-50 μM, n = 3), and were not mimicked by nicotine (50-100 μM, n = 4), indicating the involvement of muscarinic receptors. In contrast, in nonbursting cells from the same epileptic area (n = 42) or from equivalent area in control rats (n = 24), a nonsignificant muscarinic depression of EPSPs was induced by Cch and Ach. The mAch depression of excitatory postsynaptic potential (EPSPs) was significantly lower than that seen for PDSs in GWS rats. None of the cholinergic agonists caused bursting appearance in these cells. Therefore the present study demonstrates a unique implication of muscarinic receptors in exerting opposite effects on intrinsic membrane properties and on synaptic transmission in epileptiform GWS. Muscarinic receptor mechanisms may therefore have a protective role against the development and spread of epileptiform activity from the otherwise-activated epileptic focus.

Original languageEnglish
Pages (from-to)2159-2165
Number of pages7
JournalJournal of Neurophysiology
Volume85
Issue number5
Publication statusPublished - May 26 2001

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

Silva-Barrat, C., Szente, M., Menini, C., Velluti, J. C., & Champagnat, J. (2001). Muscarinic depression of synaptic transmission in the epileptogenic GABA withdrawal syndrome focus. Journal of Neurophysiology, 85(5), 2159-2165.