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Synchronous GABAA-receptor-dependent potentials in limbic areas of the in-vitro isolated adult guinea pig brain

Authors

  • Laura Uva,

    1. Unit of Experimental Neurophysiology and Epileptology, Fondazione Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy
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  • Massimo Avoli,

    1. Montreal Neurological Institute and Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada
    2. Dipartimento di Medicina Sperimentale, Sapienza Università di Roma, Rome, Italy
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  • Marco De Curtis

    1. Unit of Experimental Neurophysiology and Epileptology, Fondazione Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy
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Dr M. de Curtis, as above.
E-mail: decurtis@istituto-besta.it

Abstract

Epileptiform discharges are known to reflect the hypersynchronous glutamatergic activation of cortical neurons. However, experimental evidence has revealed that epileptiform synchronization is also contributed to by population events mediated by GABAA receptors. Here, we analysed the spatial distribution of GABAA-receptor-dependent interictal events in the hippocampal/parahippocampal region of the adult guinea pig brain isolated in vitro. We found that arterial perfusion of this preparation with 4-aminopyridine caused the appearance of glutamatergic-independent interictal potentials that were reversibly abolished by GABAA receptor antagonism. Laminar profiles and current source density analysis performed in different limbic areas demonstrated that these GABAA-receptor-mediated events were independently generated in different areas of the hippocampal/parahippocampal formation (most often in the medial entorhinal cortex) and propagated between interconnected limbic structures of both hemispheres. Finally, intracellular recordings from principal neurons of the medial entorhinal cortex demonstrated that the GABAergic field potential correlated to inhibitory postsynaptic potentials (membrane potential reversal, −68.12 ± 8.01 mV, n = 5) that were interrupted by ectopic spiking. Our findings demonstrate that, in an acute seizure model developed in the adult guinea pig brain, hypersynchronous GABAA-receptor-mediated interictal events are generated from independent sources and propagate within limbic cortices in the absence of excitatory synaptic transmission. As spared or enhanced inhibition was reported in models of epilepsy, our data may support a role of GABA-mediated signaling in ictogenesis and epileptogenesis.

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