Induction of a novel form of hippocampal long‐term depression by muscimol: involvement of GABA_A but not glutamate receptors

Abstract

1 Unlike long-term potentiation, long-term depression (LTD) 4 Adenosine decreased the spike size in a concentration-dependent manner, but failed to induce LTD. 5 Alphaxalone and 5a-pregnan-3a-ol-20-one at concentrations that did not have any effect themselves on the population spike (0.5 and 1 gM), potentiated the inhibitory effect of muscimol on the population spike size, including concentrations which were not effective by themselves. Both steroids were able to potentiate the ability of muscimol to induce LTD. 6 Bicuculline, 5 gM, reversed the LTD induced by muscimol, 10 gM. 7 The NMDA receptor antagonist (±)-2-amino-5-phosphonopentanoic acid (2-AP5), the NMDA/ metabotropic antagonist 2-AP3 and selective metabotropic antagonist L-(+)-2-amino-3-phosphonopropionic acid (L(+)-AP3) failed to modify the LTD. Similarly, quisqualic acid and (IS, 3R)-aminocyclopentane dicarboxylic acid (ACPD) a selective agonist at metabotropic receptors did not induce LTD or short-term depression, whereas kynurenic acid prevented the reversal of the LTD obtained at 1 Hz. 8 It is concluded that LTD can be induced by the selective activation of GABAA receptors. The lack of involvement of glutamate receptors in our protocol confirms the unique nature of the LTD described here. The phenomenon of GABA-induced LTD and its reversal by 1 Hz stimulation may represent a novel type of long-lasting depression by which inhibitory interneurones can modulate pyramidal cell excitability in a frequency-dependent manner.

Ethanol inhibits excitatory neurotransmission in the nucleus accumbens of adolescent mice through GABAAand GABABreceptors

“…Alternatively, this effect could underlie a form of long‐term synaptic plasticity, i.e. long‐term depression, as shown previously in the hippocampus (Akhondzadeh & Stone 1995).…”

Hippocampal Metaplasticity Induced by Deficiency in the Extracellular Matrix Glycoprotein Tenascin-R

“…That 2 h treatments were able to affect metaplasticity is not surprising because of previous reports showing rapid triggering and reversal of metaplastic changes (Abraham and Bear, 1996;Shakesby et al, 2002). Application of muscimol or zolpidem increases GABA A receptor-mediated currents and reduces spiking and excitatory postsynaptic potentials (Rovira et al, 1984;Akhondzadeh and Stone, 1995;Steele and Mauk, 1999;Hajos et al, 2000;Liang et al, 2004). Two other treatments of slices from TNRϪ/Ϫ mice, namely with the GABA B receptor antagonist CGP54626A and the HNK-1 peptidomimetic, produced a similar normalization of LTP as GABA A receptor agonists.…”

The GABAAreceptor agonist muscimol induces an age- and region-dependent form of long-term depression in the mouse striatum

“…Several neurotransmitters, such as glutamate, dopamine, adenosine, and serotonin contribute to the induction of endocannabinoid-dependent LTD in the striatum (Lovinger 2010;Tozzi et al 2011;Lerner and Kreitzer 2012;Burattini et al 2014). Although GABA is the most important inhibitory neurotransmitter in the brain, few studies have examined its ability to induce synaptic plasticity at glutamatergic synapses (Akhondzadeh and Stone 1995). We recently found that the GABA A receptor agonist muscimol induced a long-lasting inhibition of glutamatergic synaptic transmission in the NAc in adolescent but not adult mice (Mishra and Chergui 2013).…”