GABA B-receptor modulation of short-term synaptic depression at an excitatory input to murine hippocampal CA3 pyramidal neurons

Abstract

GABA B agonists inhibit excitatory transmission to hippocampal CA3 neurons during low frequency stimulation. We examined whether GABA B receptor activation can also enhance synaptic efficacy, when investigated at an input with high initial release probability. Short-term depression of field excitatory postsynaptic potential (EPSP) amplitude was observed during trains of stimuli applied to associational/commissural inputs (10–50 Hz; 22 °C). Baclofen (10 μM) reduced the amplitude of initial EPSPs in a train, and also reduced the degree of short-term depression. EPSPs recorded late in a train were significantly larger in baclofen than those recorded in control solution. These dual effects were mimicked by another selective GABA B agonist (SKF 97541, 10 μM), and abolished by a GABA B-selective antagonist (SCH 50911, 20 μM). The effects of baclofen were similar at a higher recording temperature (32 °C), where short-term depression was observed at higher stimulation frequencies. These results are consistent with the idea that a reduction of transmitter release probability could increase the fidelity of high-frequency transmission at this input, an effect that could help account for excitatory effects of GABA B agonists in some seizure models.