GABAergic input onto CA3 hippocampal interneurons remains shunting throughout development
GABAergic input onto CA3 hippocampal interneurons remains shunting throughout development
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DOI：
10.1523/jneurosci.2887-06.2006
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发表时间：
2006-11-08
影响因子：
5.3
通讯作者：
McBain, Chris J.
中科院分区：
文献类型：
--
作者：
Banke, Tue G.;McBain, Chris J.
在海马中，兴奋性的净流量由许多局部回路抑制性中间神经元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一个高度协调的转变，从生命早期的去极化到成熟时更常规的超极化抑制。抑制性输入极性的这种转换是由两个氯离子协同转运蛋白（NKCC 1和KCC 2）的发育调节控制的，这导致细胞内Cl-从高到低的净转移。是否抑制性输入抑制性中间神经元表现出类似的发展变化，在细胞内的Cl-是未知的。使用短杆菌肽穿孔补丁配置，我们记录从CA 3海马透明层中间神经元和锥体细胞监测抑制输入在广泛的发展范围。GABAA受体介导的对透明层抑制性中间神经元的突触输入在整个测试的发育年龄范围内本质上是分流的，因为静息膜电位和IPSC逆转电位在出生后第5天（P5）和P31之间保持在几毫伏（1 - 4 mV）内。此外，在相同的年龄范围内，两种氯协同转运蛋白KCC 2和NKCC 1对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，锥体细胞突触抑制证明了在相同年龄范围内从去极化到超极化的充分描述的转变。因此，与主细胞相反，对CA 3中间神经元的抑制性突触输入在整个发育过程中保持分流。
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. GABAA 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 - 4mV) 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.