Elsevier

Neuropharmacology

Volume 37, Issue 9, September 1998, Pages 1111-1122
Neuropharmacology

GABA-induced long-term potentiation in the guinea-pig superior colliculus

https://doi.org/10.1016/S0028-3908(98)00100-2Get rights and content

Abstract

Although GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the brain, intense activation of GABA receptors can cause excitation under certain conditions. In the superficial layers of the guinea-pig superior colliculus (SC) slice the excitatory action of GABA (≤3 mM) is dominant and sufficient to induce a robust and novel form of long-term potentiation, termed LTPG, of evoked field excitatory postsynaptic potentials (fEPSPs). This action of GABA could neither be mimicked by GABA-A nor -B agonists which were found to suppress synaptic transmission. Additionally, LTPG was not inhibited by the GABA-A receptor antagonist bicuculline while the GABA-C receptor antagonist imidazol-4-acetic acid prevented LTPG. Glutamatergic synaptic transmission was found to be required, as LTPG was partially use-dependent and did not emerge when glutamate receptors of the non-NMDA type were blocked during GABA application. Moreover, LTPG declined to baseline values in the presence of the NMDA antagonist d,l-2-amino-5-phosphonovaleric acid (APV). In addition, the L-type calcium channel blocker nifedipine inhibited the induction of LTPG. It is suggested that activation of excitatory GABA non-A, non-B receptors can lead to LTP in the SC, which may be of major importance for plastic events since the content of GABA and GABA receptors are particularly high in this brain area.

Introduction

γ-Aminobutyric acid (GABA) receptors can be divided into three subclasses: GABA-A, -B and -C receptors. Bicuculline-sensitive GABA-A and bicuculline-insensitive GABA-C receptors are associated with an ion channel selectively permeable for chloride (Cl) and bicarbonate (HCO3), whereas GABA-B receptors couple to Ca2+ and K+ channels via G-proteins and intracellular second messenger systems (Bormann, 1988, Bormann and Feigenspann, 1995). The GABA-C receptor has only recently been studied at the molecular level and has, so far, been investigated in detail only in the retina (Quian and Dowling, 1993, Quian and Dowling, 1995) and in expression systems such as oocytes (Kusama et al., 1993a, Kusama et al., 1993b).

Although GABA is the main inhibitory neurotransmitter in the central nervous system it can also depolarise neurones under certain conditions for instance in the hippocampus of neonatal rats (Cherubini et al., 1991, Strata and Cherubini, 1994, Martina et al., 1995, Ben-Ari et al., 1997). In this context, GABA was found to increase intracellular calcium via the activation of voltage-dependent calcium channels (VDCCs, Reichling et al., 1994, Leinekugel et al., 1995, Obrietan and van den Pol, 1995) which appears to play a major role in early development (Cherubini et al., 1991, LoTurco et al., 1995, Obrietan and van den Pol, 1996), but also after neuronal injury (Van den Pol et al., 1996). In addition, strong activation of GABA-A receptors was reported to cause a biphasic inhibitory/excitatory response in distal dendrites of the mature hippocampus (Alger and Nicoll, 1979, Andersen et al., 1980, Lambert et al., 1991) which could also be observed after 200 Hz stimulation (Grover et al., 1993).

The superior colliculus (SC) is a multi-layered midbrain nucleus which shows various forms of plasticity such as tetanus-induced long-term potentiation (LTP, Miyamoto et al., 1990) habituation (Platt and Withington, 1997a) and paired-pulse depression (Platt and Withington, 1997c). GABA has been described as a major transmitter beside the excitatory neurotransmitter glutamate. In fact, approximately 50% of SC neurones show GABA-labelling and highest concentrations of GABA and glutamate decarboxylase, the GABA synthesising enzyme are found in this brain area (Mize, 1992). Three different types of GABA-labelled neurones have been identified in the SC, with the densest distribution of GABA receptors found in the superficial layers (Mize, 1992, Okada, 1992). Application of GABA was described to cause both an enhancement and depression of evoked postsynaptic potentials in SC slices of adult guinea-pigs, depending on the concentration used (Arakawa and Okada, 1988). Interestingly, GABA-mediated excitation could also be induced by applying the GABA-uptake inhibitor nipecotic acid. In this paper, the authors attributed the excitatory action of GABA to GABA-A and the inhibitory action to GABA-B receptor activation. However, application of GABA-A antagonists caused clear signs of disinhibition in SC slices (Arakawa and Okada, 1988, Platt and Withington, 1997a, Platt and Withington, 1997c) and tetanus-induced in vivo LTP could only be induced in the presence of GABA-A antagonists (Hirai and Okada, 1993) suggesting inhibitory rather than excitatory GABA-A mediated responses. In the frog optic tectum (the homologue of the SC in amphibians), an excitatory action of GABA was reported which was insensitive to the specific GABA-A antagonist bicuculline (Nistri and Sivilotti, 1985, Sivilotti and Nistri, 1989). Similar evidence for bicuculline- and baclofen-insensitive excitatory GABA receptors in early postnatal life was provided for instance in the hippocampal slice preparation (Strata and Cherubini, 1994, Martina et al., 1995).

The aim of the present study was to characterise pharmacologically the unusual excitatory action of GABA in SC slices of adult guinea pigs, and the consequences of GABA-induced excitation on synaptic transmission. A preliminary report of some of the data presented here has already appeared in abstract form (Platt and Withington, 1997b).

Section snippets

Methods

A detailed description of the experimental procedures can be found elsewhere (Platt and Withington, 1997c). Briefly, anaesthetised adult guinea-pigs (>50 days) were decapitated and the brains were quickly transferred into ice-cold Ringer solution (composition in mM: NaCl 125, KCl 5, MgCl2 1.3, CaCl2 2.5, KH2PO4 1.2, glucose 10, NaHCO3 25; saturated with 95% O2/5% CO2, pH 7.4,). Sagittal SC slices (400 μm) were prepared using a vibratome. After 60 min of equilibration at 32°C, slices were placed

GABA causes a long-lasting enhancement of synaptic transmission

During superfusion of GABA (300 μM–3 mM) an enhancement of the fEPSP recorded in the SGL of the SC (see Fig. 1A for experimental design) was seen which is in agreement with the reports of others (Arakawa and Okada, 1988, Okada, 1992).

When GABA was applied for 7 min, however, the enhancement of the fEPSP was found to be sustained and lasted for at least 1 h after washout. We propose that this type of long-lasting increase of synaptic efficacy, termed `GABA-induced long-term potentiation' (LTPG),

The excitatory action of GABA is not mediated through GABA-A or -B receptors

Our data show that application of GABA (≤3 mM) caused an enhancement of evoked fEPSPs in the superficial layers of the SC leading to a novel form of long-term potentiation, LTPG. For the 3 mM group, the increase of the slope was maintained after removal of GABA while it declined partially when induced by 500 μM indicating the concentration-dependence of LTPG. The enhancement of the fEPSP slope during superfusion of 3 mM GABA was slightly weaker than the one observed during application of 500 μM

Acknowledgements

BP was supported by the European Community, DJW is a senior MRC Research Fellow.

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