Synchronization of GABAergic inputs to CA3 pyramidal cells precedes seizure-like event onset in juvenile rat hippocampal slices

Bálint Lasztóczi, G. Nyitrai, László Héja, J. Kardos

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Abstract

Here we address how dynamics of glutamatergic and GABAergic synaptic input to CA3 pyramidal cells contribute to spontaneous emergence and evolution of recurrent seizure-like events (SLEs) in juvenile (P10-13) rat hippocampal slices bathed in low-[Mg2+] artificial cerebrospinal fluid. In field potential recordings from the CA3 pyramidal layer, a short epoch of high-frequency oscillation (HFO; 400-800 Hz) was observed during the first 10 ms of SLE onset. GABAergic synaptic input currents to CA3 pyramidal cells were synchronized and coincided with HFO, whereas the glutamatergic input lagged by ∼10 ms. If the intracellular [Cl-] remained unperturbed (cell-attached recordings) or was set high with whole cell electrode solution, CA3 pyramidal cell firing peaked with HFO and GABAergic input. By contrast, with low intracellular [Cl-], spikes of CA3 pyramidal cells lagged behind HFO and GABAergic input. This temporal arrangement of HFO, synaptic input sequence, synchrony of GABAergic currents, and pyramidal cell firing emerged gradually with preictal discharges until the SLE onset. Blockade of GABA A receptor-mediated currents by picrotoxin reduced the inter-SLE interval and the number of preictal discharges and did not block recurrent SLEs. Our data suggest that dynamic changes of the functional properties of GABAergic input contribute to ictogenesis and GABAergic and glutamatergic inputs are both excitatory at the instant of SLE onset. At the SLE onset GABAergic input contributes to synchronization and recruitment of pyramidal cells. We conjecture that this network state is reached by an activity-dependent shift in GABA reversal potential during the preictal phase.

Original languageEnglish
Pages (from-to)2538-2553
Number of pages16
JournalJournal of Neurophysiology
Volume102
Issue number4
DOIs
Publication statusPublished - Oct 2009

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Pyramidal Cells
Seizures
Picrotoxin
GABA-A Receptors
gamma-Aminobutyric Acid
Cerebrospinal Fluid
Electrodes

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Synchronization of GABAergic inputs to CA3 pyramidal cells precedes seizure-like event onset in juvenile rat hippocampal slices. / Lasztóczi, Bálint; Nyitrai, G.; Héja, László; Kardos, J.

In: Journal of Neurophysiology, Vol. 102, No. 4, 10.2009, p. 2538-2553.

Research output: Contribution to journalArticle

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