When considering the mechanisms that underlie activity-dependent changes in synaptic strength, researchers have often focused solely on changes in the probability of transmitter release or in the responsiveness of the postsynaptic cell. In a recent paper in the Journal of Physiology, Engel and colleagues draw attention to another potential source of variation in synaptic efficacy — the metabolism of neurotransmitter and its effect on the filling of synaptic vesicles.

The production of the inhibitory transmitter GABA (γ-aminobutyric acid) is known to vary in response to changes in neuronal activity. But could regulated fluctuations in vesicular GABA content represent a mechanism of plasticity at inhibitory synapses? To examine this possibility, Engel et al. used pharmacological tools to increase or decrease the presynaptic GABA content of interneurons in cultured hippocampal slices. The effects of GABA release were assessed by monitoring spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in CA3 pyramidal cells. They found that blocking the degradation of GABA led to an increase in the amplitude and frequency of GABAA-receptor-mediated mIPSCs; conversely, the suppression of GABA synthesis was associated with a decrease in these measures.

These data are evidence of a direct relationship between synaptic efficacy and GABA metabolism at a central synapse. It will be interesting to determine whether fluctuations in GABA content can lead to short-term, activity-dependent changes in the strength of inhibitory synapses. But more importantly, these findings might have parallels at excitatory synapses, which would further challenge the commonly made assumptions about the reliability of quantal analysis in the central nervous system.