Synchronized GABAergic IPSPs recorded in the neocortex after blockade of synaptic transmission mediated by excitatory amino acids

Abstract

1. Intracellular and extracellular recordings were carried out in guinea pig neocortical slices to examine the effects of blockade of excitatory amino acid (EAA) synaptic transmission on population discharges elicited by 4-aminopyridine (4-AP; 50-100 microM). 2. After the introduction of 4-AP, two distinct types of rhythmic spontaneous field potentials were recorded in neocortical slices. Type I consisted of multiple spike discharges lasting 20-90 s. These events occurred at a frequency of 0.4-0.2/min. Type II were single field potential spikes (3-6 s in duration) occurring at a higher frequency (2-4/min). 3. Blockade of amino acid-mediated excitatory synaptic transmission with D-2-amino-5-phosphonovaleric acid (D-AP5; 10-30 microM) or 3-(2-carboxypiperazin-4-yl)propyl-l-phosphonic acid (CPP, 10 microM) and 6-cyano-7nitroquinoxaline-2,3-dione (CNQX; 10 microM) abolished the first type of 4-AP-induced field potential, whereas type II events persisted. 4. Type II field events, occurring in the presence of EAA blockers, were further characterized by paired recordings. Events recorded along an axis orthogonal to the pia surface occurred simultaneously without measurable delay. Recordings made along a plane parallel to the pia surface showed that type II discharges propagated over distances of greater than or equal to 3 mm at an estimated velocity of 7.5 mm/s. 5. Intracellular recordings show that during type II field discharges all cells exhibited phasic depolarizations or hyperpolarizations, depending on the resting membrane potential. When resting potentials were more depolarized than -68 mV, events became mostly hyperpolarizing.(ABSTRACT TRUNCATED AT 250 WORDS)

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

“…The contribution of GABA A receptors to the 4AP-induced slow, interictal events recorded during blockade of glutamatergic receptors is further supported by intracellular data obtained from principal cells in the neocortex (Aram et al, 1991;Avoli et al, 1994), hippocampus (Perreault and Avoli, 1992) and in other limbic areas such as the amygdala or the entorhinal cortex. In all cases, the counterpart of the slow discharges that continue to occur in the presence of glutamatergic receptor antagonists is a sequence of hyperpolarizingdepolarizing potentials that change in amplitude as expected for a post-synaptic response due to Cl − conductances (Fig.…”

“…Moreover, Benardo (1997) has shown that during 4AP application neocortical interneurons generate sustained action potential firing. Finally, long-lasting depolarizations with associated firing have been reported to occur in principal cells of the neocortex (Aram et al, 1991;Avoli et al, 1994) and of the cingulate cortex (Panuccio et al, 2009) during 4AP treatment.…”

4-aminopyridine-induced epileptiform activity and a GABA-mediated long- lasting depolarization in the rat hippocampus

“…This is supported by the fact that LLDs remained coupled in all areas of the slice after the addition of both NMDA and non-NMDA antagonists that block fast synaptic transmission of many pathways in the hippocampus (Neumann et al, 1988;Davies and Collingridge, 1989;Lambert et al, 1989). Recent observations in the neocortex have also shown that the occurrence of GABA-mediated slow depolarizations is resistant to excitatory amino acid antagonists (Aram et al, 1991).…”

Epileptiform synchronization in the rat insular and perirhinal cortices in vitro

“…Currently, there is strong evidence favouring GABA, not glutamate, as the important excitatory neurotransmitter coordinating neuronal network maturation during development by inducing giant depolarizing potentials (GDPs; Ben-Ari et al, 1989;Kasyanov et al, 2004;Krnjevic, 2004;Ben-Ari and Holmes,2005). GABA has also been observed to exert excitatory postsynaptic effects in adult hippocampal slices in response to high frequency stimulation or intense dendritic activation (Staley et al, 1995;Lamsa and Taira, 2003;Krnjevic, 2004), and in the presence of 4AP (Perreault and Avoli, 1989;Aram et al, 1991;Michelson and Wong, 1991;Lamsa and Kaila, 1997).…”