Development of GABAAReceptor-Mediated Inhibitory Postsynaptic Currents in Hippocampus

Open Access
Publisher Website
Google Scholar
Abstract
Hippocampal CA1 pyramidal cells receive two kinetic classes of GABAAreceptor-mediated inhibition: slow dendritic inhibitory postsynaptic currents (GABAA,slowIPSCs) and fast perisomatic (GABAA,fast) IPSCs. These two classes of IPSCs are likely generated by two distinct groups of interneurons, and we have previously shown that the kinetics of the IPSCs have important functional consequences for generating synchronous firing patterns. Here, we studied developmental changes in the properties of GABAA,fastand GABAA,slowspontaneous, miniature, and evoked IPSCs (sIPSCs, mIPSCs, and eIPSCs, respectively) using whole cell voltage-clamp recordings in brain slices from animals aged P10–P35. We found that the rate of GABAA,slowsIPSCs increased by over 70-fold between P11 and P35 (from 0.0017 to 0.12 s−1). Over this same age range, we observed a >3.5-fold increase in the maximal amplitude of GABAA,sloweIPSCs evoked by stratum lacunosum-moleculare (SL-M) stimuli. However, the rate and amplitude of GABAA,slowmIPSCs remained unchanged between P10 and P30, suggesting that the properties of GABAA,slowsynapses remained stable over this age range, and that the increase in sIPSC rate and in eIPSC amplitude was due to increased excitability or excitation of GABAA,slowinterneurons. This hypothesis was tested using bath application of norepinephrine (NE), which we found at low concentrations (1 μM) selectively increased the rate of GABAA,slowsIPSCs while leaving GABAA,fastsIPSCs unchanged. This effect was observed in animals as young as P13 and was blocked by coapplication of tetrodotoxin, suggesting that NE was acting to increase the spontaneous firing rate of GABAA,slowinterneurons and consistent with our hypothesis that developmental changes in GABAA,slowIPSCs are due to changes in presynaptic excitability. In contrast to the changes we observed in GABAA,slowIPSCs, the properties of GABAA,fastsIPSCs remained largely constant between P11 and P35, whereas the rate, amplitude, and kinetics of GABAA,fastmIPSCs showed significant changes between P10 and P30, suggesting counterbalancing changes in action potential-dependent GABAA,fastsIPSCs. These observations suggest differential developmental regulation of the firing properties of GABAA,fastand GABAA,slowinterneurons in CA1 between P10 and P35.