Banke Tue G, McBain Chris J
Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Neurosci. 2006 Nov 8;26(45):11720-5. doi: 10.1523/JNEUROSCI.2887-06.2006.
In hippocampus, the net flow of excitability is controlled by inhibitory input provided by the many populations of local circuit inhibitory interneurons. In principal cells, GABA(A) receptor-mediated synaptic input undergoes a highly coordinated shift from depolarizing early in life to a more conventional hyperpolarizing inhibition on maturation. This switch in inhibitory input polarity is controlled by the developmental regulation of two chloride cotransporters (NKCC1 and KCC2) that results in a net shift from high to low intracellular Cl(-). Whether inhibitory input onto inhibitory interneurons demonstrates a similar developmental shift in intracellular Cl(-) is unexplored. Using the gramicidin perforated-patch configuration, we recorded from CA3 hippocampal stratum lucidum interneurons and pyramidal cells to monitor inhibitory input across a broad developmental range. GABA(A) receptor-mediated synaptic input onto stratum lucidum inhibitory interneurons was shunting in nature across the entire developmental age range tested, as resting membrane potential and the IPSC reversal potential remained within a few millivolts (1-4 mV) between postnatal day 5 (P5) and P31. Furthermore, sensitivity to block of the two chloride cotransporters KCC2 and NKCC1 did not differ across the same age range, suggesting that their relative expression is fixed across development. In contrast, pyramidal cell synaptic inhibition demonstrated the well described switch from depolarizing to hyperpolarizing over the same age range. Thus, in contrast to principal cells, inhibitory synaptic input onto CA3 interneurons remains shunting throughout development.
在海马体中，兴奋性的净流动由许多局部回路抑制性中间神经元群体提供的抑制性输入控制。在主细胞中，GABA(A)受体介导的突触输入经历了从生命早期的去极化到成熟时更传统的超极化抑制的高度协调转变。抑制性输入极性的这种转变由两种氯共转运体（NKCC1和KCC2）的发育调节控制，这导致细胞内氯离子从高到低的净转变。抑制性中间神经元上的抑制性输入在细胞内氯离子方面是否表现出类似的发育转变尚不清楚。我们使用短杆菌肽穿孔膜片钳配置，从CA3海马体透明层中间神经元和锥体细胞进行记录，以监测广泛发育范围内的抑制性输入。在整个测试的发育年龄范围内，GABA(A)受体介导的突触输入到透明层抑制性中间神经元本质上是分流性的，因为静息膜电位和IPSC反转电位在出生后第5天（P5）到P31之间保持在几毫伏（1-4 mV）以内。此外，在相同年龄范围内，对两种氯共转运体KCC2和NKCC1阻断的敏感性没有差异，这表明它们的相对表达在整个发育过程中是固定的。相比之下，锥体细胞突触抑制在相同年龄范围内表现出从去极化到超极化的转变，这是众所周知的。因此，与主细胞不同，CA3中间神经元上的抑制性突触输入在整个发育过程中仍然是分流性的。
