Activity-dependent scaling of GABAergic excitation by dynamic Cl- changes in Cajal-Retzius cells

To unravel the functional implications of activity-dependent Cl- changes during early stages of neuronal development, we determined which changes in the GABA reversal potential (E (GABA)) and GABAergic rheobase shifts were induced by episodes of GABA(A) receptor activation using gramicidin-perforated patch-clamp recordings from Cajal-Retzius cells in tangential cortical slices of newborn mice. Under this condition, focal application of the GABA(A) agonist muscimol (10 μM) depolarized the membrane by 15 ± 0.8 mV (n = 35). Such subthreshold GABAergic depolarizations considerably reduced the rheobase, corresponding to an excitatory action. After repetitive focal muscimol applications (50 pulses at 0.5 Hz) a significant reduction of E (GABA) and an attenuation of the excitatory GABAergic rheobase shift were observed, while the GABAergic membrane conductance and the absolute value of the rheobase were unaltered after the muscimol pulses. Bath application of 100 μM carbachol induced bursts of spontaneous GABAergic postsynaptic potentials. Both, E (GABA) and the excitatory GABAergic rheobase shift was significantly reduced after such barrage of carbachol-induced GABAergic postsynaptic potentials, while neither the GABAergic membrane conductance nor the absolute value of the rheobase was affected under this condition. Both results indicate that GABAergic activity itself can limit the excitatory effects of GABA(A) receptor activation, which supports the hypothesis that the low capacity of the Cl- homeostasis in immature neurons could be a substrate for synaptic scaling and homeostatic plasticity.