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Developmental change in GABA_A receptor desensitization kinetics and its role in synapse function in rat cortical neurons

Bruce Hutcheon, Paul Morley and Michael O. Poulter

1. We examined the maturation of GABA_A receptor synapses in cortical pyramidal neurons cultured from embryonic rats. The decay kinetics of GABA_A receptor-mediated miniature postsynaptic currents (mPSCs) were compared with those of responses evoked by GABA in excised membrane patches.

2. Fast perfusion of 1 or 10 mM GABA on membrane patches evoked currents with different desensitizing time courses in young and old neurons. For neurons older than 4 days in vitro (DIV), GABA_A currents had a fast component of desensitization (median 3 ms) seldom seen in patches from younger neurons. In contrast, mPSCs exhibited a substantial fast component of decay at 2-4 DIV that became more prominent with further development although the median value of its time constant remained unchanged.

3. The selective 3 subunit positive modulator SB-205384 had no effect on mPSCs at any time in vitro but potentiated extrasynaptic activity. This suggests that synapse maturation does not proceed by a gradual exchange of early embryonic GABA_A receptor subforms for adult forms.

4. At all ages, the kinetic properties of mPSCs were heterogeneous. This heterogeneity extended to the level of mPSCs from single neurons and may be a normal aspect of synaptic functioning.

5. These results suggest that inhibitory synapses in developing neurons are capable of selectively capturing GABA_A receptors having fast desensitization kinetics. This functional preference probably reflects the developmental turning point from an inwardly looking trophic capacity of embryonic GABA_A receptors to a role concerned with information processing.

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