Excitatory Synaptic Responses Mediated by GABA _A Receptors in the Hippocampus

Abstract

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the cortex. Activation of postsynaptic GABAA receptors hyperpolarizes cells and inhibits neuronal activity. Synaptic responses mediated by GABAA receptors also strongly excited hippocampal neurons. This excitatory response was recorded in morphologically identified interneurons in the presence of 4-aminopyridine or after elevation of extracellular potassium concentrations. The synaptic excitation sustained by GABAA receptors synchronized the activity of inhibitory interneurons. This synchronized discharge of interneurons in turn elicited large-amplitude inhibitory postsynaptic potentials in pyramidal and granule cells. Excitatory synaptic responses mediated by GABAA receptors may thus provide a mechanism for the recruitment of GABAergic interneurons through their recurrent connections.

Models of drug-induced epileptiform synchronization in vitro

“…Shortly after, Voskuyl and Albus (1985) identified 2 types of spontaneous, interictal-like field potentials in isolated hippocampal slices; the first type resembled the spontaneous epileptiform activity induced by GABA A receptor antagonists and originated in the CA3 subfield, while the second lasted longer, spread at slower velocity and was resistant to glutamatergic receptor antagonism. These results were later confirmed by other investigators (Rutecki et al, 1987;Michelson and Wong, 1991;Perreault and Avoli, 1992;Watts and Jefferys, 1993).…”

“…The "slow" glutamatergic-independent spikes recorded in the CA3 subfield during 4AP application are associated with transient increases in extracellular [K + ] that are caused by the activation of GABA A receptors following the release of GABA from interneurons (Morris et al, 1996). In line with this view, Benardo (1997) has found in rat neocortical slices that interneurons generate periodic action potential firing in the presence of 4AP and excitatory transmission blockers while large amplitude IPSPs occur rhythmically in pyramidal cells; he also suggested that under these pharmacological conditions, interneurons are synchronized through electrotonic coupling and recurrent collaterals (which release GABA thus causing postsynaptic GABA A receptor depolarizations as proposed in the hippocampus by Michelson and Wong, 1991).…”

Relationships Among Seizures, Extracellular Amino Acid Changes, and Neurodegeneration Induced by 4‐Aminopyridine in Rat Hippocampus: A Microdialysis and Electroencephalographic Study

“…The resultant increase in extracellular glutamate content was not as dramatic as that previously observed in the striatum, and this change by itself cannot account for the convulsive activity, because it was observed only with the three highest 4-AP concentrations used, whereas the epileptiform discharges occurred also with lower concentrations. The remarkable enhancement of extracellular GABA induced by 4-AP might also be involved in the hyperexcitation, because it has been repeatedly shown in hippocampal slices that under conditions of neuronal overactivity (Staley et al, 1995;Kaila et al, 1997;Labrakakis et al, 1997), including that induced by 4-AP (Michelson and Wong, 1991;Perrault and Avoli, 1992;Lamsa and Kaila, 1997;Siniscalchi et al, 1997), the synaptic action of this neurotransmitter changes from inhibitory to excitatory. Nonetheless, as with glutamate, GABA content increases were observed only with the highest 4-AP concentrations.…”

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

“…Interneuron communication is provided by glutamatergic transmission (Lacaille, 1991) but also by GABA A receptor postsynaptic currents that are frankly excitatory (Michelson and Wong, 1991) along with gap junctions containing specific types of connexin proteins (Gibson et al, 1999(Gibson et al, , 2004Traub et al, 2003Traub et al, , 2004Mancilla et al, 2007).…”