Banks Matthew I, Hardie Jason B, Pearce Robert A
Department of Anesthesiology and Neuroscience Training Program, University of Wisconsin, Madison, Wisconsin 53706, USA.
J Neurophysiol. 2002 Dec;88(6):3097-107. doi: 10.1152/jn.00026.2002.
Hippocampal CA1 pyramidal cells receive two kinetic classes of GABA(A) receptor-mediated inhibition: slow dendritic inhibitory postsynaptic currents (GABA(A,slow) IPSCs) and fast perisomatic (GABA(A,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 GABA(A,fast) and GABA(A,slow) spontaneous, 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 GABA(A,slow) sIPSCs 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 GABA(A,slow) eIPSCs evoked by stratum lacunosum-moleculare (SL-M) stimuli. However, the rate and amplitude of GABA(A,slow) mIPSCs remained unchanged between P10 and P30, suggesting that the properties of GABA(A,slow) synapses 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 GABA(A,slow) interneurons. This hypothesis was tested using bath application of norepinephrine (NE), which we found at low concentrations (1 microM) selectively increased the rate of GABA(A,slow) sIPSCs while leaving GABA(A,fast) sIPSCs 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 GABA(A,slow) interneurons and consistent with our hypothesis that developmental changes in GABA(A,slow) IPSCs are due to changes in presynaptic excitability. In contrast to the changes we observed in GABA(A,slow) IPSCs, the properties of GABA(A,fast) sIPSCs remained largely constant between P11 and P35, whereas the rate, amplitude, and kinetics of GABA(A,fast) mIPSCs showed significant changes between P10 and P30, suggesting counterbalancing changes in action potential-dependent GABA(A,fast) sIPSCs. These observations suggest differential developmental regulation of the firing properties of GABA(A,fast) and GABA(A,slow) interneurons in CA1 between P10 and P35.
海马体CA1锥体细胞接受两类动力学的GABA(A)受体介导的抑制作用：缓慢的树突抑制性突触后电流（GABA(A,slow) IPSCs）和快速的胞体周围（GABA(A,fast)）IPSCs。这两类IPSCs可能由两组不同的中间神经元产生，并且我们之前已经表明，IPSCs的动力学对于产生同步放电模式具有重要的功能影响。在这里，我们使用全细胞电压钳记录技术，研究了P10 - P35年龄段动物脑片中GABA(A,fast)和GABA(A,slow)的自发性、微小性和诱发性IPSCs（分别为sIPSCs、mIPSCs和eIPSCs）特性的发育变化。我们发现，在P11到P35之间，GABA(A,slow) sIPSCs的频率增加了70多倍（从0.0017增加到0.12 s(-1)）。在相同的年龄范围内，我们观察到由腔隙分子层（SL - M）刺激诱发的GABA(A,slow) eIPSCs的最大幅度增加了3.5倍以上。然而，GABA(A,slow) mIPSCs的频率和幅度在P10到P30之间保持不变，这表明在这个年龄范围内，GABA(A,slow)突触的特性保持稳定，并且sIPSC频率和eIPSC幅度的增加是由于GABA(A,slow)中间神经元的兴奋性增加或受到的兴奋增强。我们使用浴加去甲肾上腺素（NE）来验证这一假设，我们发现在低浓度（1 microM）时，NE选择性地增加了GABA(A,slow) sIPSCs的频率，而GABA(A,fast) sIPSCs保持不变。在P13及以上的动物中观察到了这种效应，并且被同时应用河豚毒素所阻断，这表明NE的作用是增加GABA(A,slow)中间神经元的自发放电频率，这与我们的假设一致，即GABA(A,slow) IPSCs的发育变化是由于突触前兴奋性的改变。与我们在GABA(A,slow) IPSCs中观察到的变化相反，GABA(A,fast) sIPSCs的特性在P11到P35之间基本保持不变，而GABA(A,fast) mIPSCs的频率、幅度和动力学在P10到P30之间显示出显著变化，这表明与动作电位相关的GABA(A,fast) sIPSCs存在平衡变化。这些观察结果表明，在P10到P35之间，CA1区GABA(A,fast)和GABA(A,slow)中间神经元的放电特性受到不同的发育调节。
