Synchronization of inhibitory neurones in the guinea‐pig hippocampus in vitro.

Abstract

1. Intracellular recordings were obtained from pyramidal, granule and hilar cells in transverse slices of guinea-pig hippocampus to examine synaptic interactions between GABAergic neurones. 2. In the presence of the convulsant compound 4-aminopyridine (4-AP), after fast excitatory amino acid (EAA) neurotransmission was blocked pharmacologically, large amplitude inhibitory postsynaptic potentials (IPSPs) occurred rhythmically (every 4-8 s) and synchronously in all principal cell populations (triphasic synchronized IPSPs). In the presence of the GABAA receptor blocker picrotoxin (PTX), a large amplitude IPSP continued to occur spontaneously in all principal cells simultaneously (monophasic synchronized IPSP). 3. Burst firing occurred simultaneously in a group of hilar neurones (synchronized bursting neurones) coincident with triphasic synchronized IPSPs in principal cells. After PTX was added, the bursts and the underlying depolarizing synaptic potentials were completely suppressed in some of the synchronized bursting neurones (type I hilar neurones), while others (type II hilar neurones) continued to fire in bursts coincident with monophasic synchronized IPSPs in principal cells. Intense hyperpolarization blocked burst firing and revealed underlying attenuated spikes of less than 10 mV, but did not uncover any underlying depolarizing synaptic potentials. 4. In type II hilar neurones, during sufficient hyperpolarization, spontaneous activity consisted of attenuated spikes. With depolarization, the small spikes began to trigger full size action potentials. These data suggest the presence of electrotonically remote spike initiation sites. 5. The morphology of synchronized bursting neurones was revealed by intracellular injection of the fluorescent dye Lucifer Yellow. Attempts to inject dye into one type II hilar neurone often resulted in the labelling of two to four cells (dye coupling). Dye coupling was not observed in type I hilar neurones. 6. These findings indicate that excitatory interactions synchronizing the firing of GABAergic neurones can occur in the absence of fast EAA neurotransmission. GABAergic neurones can become synchronized via their recurrent collaterals through the depolarizing action of synaptically activated GABAA receptors. In addition, a subpopulation of GABAergic neurones can become synchronized by a mechanism probably involving electrotonic coupling.Until recently, experiments addressing cellular and isolation from excitatory synaptic transmission can only be synaptic properties of cortical neurones have mainly obtained under very restrictive conditions such as direct focused on the excitatory pyramidal cells (Andersen, paired recording and antidromic stimulation (Miles &

Anin vitroblood–brain barrier model: Cocultures between endothelial cells and organotypic brain slice cultures

“…As Glu concentration can be 1,000-fold higher in the blood than in the extracellular space of the brain, a barrier to this amino acid is essential to allow a normal neuronal and synaptic activity (1). In contrast, picrotoxin, a ␥-aminobutyric acid antagonist, can easily cross the BBB and can induce epilepsy in animals (67,68). Our results indicate that Glu was prevented from reaching the nervous tissue in the coculture assemblies, whereas the picrotoxin epileptogenic effect was observed, as expected, in both control and cocultures.…”

Epileptiform synchronization in the rat insular and perirhinal cortices in vitro

“…4AP application results in downregulation of the KCC2 co-transporter in hippocampal slices, resulting in intracellular CI-accumulation and hence depolarizing postsynaptic responses to GABA (Rivera et aL, 2004). It is thus possible that these potentials were not completely abolished despite the presence of DAGO due to strong somatic excitation mediated by interneuron recurrent collateral release of depolarizing GABA, to lead to large synchronized interneuronal network discharges (Michelson and Wong, 1994 (Delfs et aL, 1994;Burkey et aL, 1996;Jasmin et aL, 2003). The increased abundance of IJ-opioid receptors within the IC therefore may account for differences in response to DAGO between the PC and the IC, however more experimentation would be necessary to determine precisely how these phenomena relate.…”

“…In the hippocampus and neocortex, these potentials are the result of synchronized discharges of interneuronal networks Michelson and Wong, 1994;Avoli et aL, 1996;Lamsa and Kaila, 1997), and appear to play a role in the initiation of in vitro ictal discharges in the EC . We found that these potentials occur within the PC and the IC synchronously without a preferential site of initiation.…”

“…It was recently shown that a similar process may contribute toward the ability of 4AP to induce depolarizing GABA responses. The KCC2 co-transporter is downregulated following periods of prolonged network activity such as during convulsant-induced epileptiform discharging (Rivera et aL, 2004), and in response to kindling in vivo (Rivera et aL, 2002 Avo li , 1989, 1992;Avoli et aL, 1994;Michelson and Wong, 1994;Avoli, 1996;Avoli et aL, 1996;Lamsa and Kaila, 1997), providing a convenient model for the study of GABA-driven interneuronal network synchronization. These potentials are GABAA receptor-dependent, implying that depolarizing GABA contributes to these large-scale network responses.…”

Gap Junctions and Emergent Rhythms

“…There is now little doubt that gap junctions play a substantial role in the generation of neural rhythms [28,5], both functional [25,1,28,5] and pathological [17,51]. One natural question therefore is how does the presence of gap junction coupling affect synchronous neuronal firing [40,24,4]. Independent experimental studies have proposed that gaps synchronize neuronal firing even in the absence of chemical synapses [16,37].…”