An essential role for modulation of hyperpolarization-activated current in the development of binaural temporal precision.
An essential role for modulation of hyperpolarization-activated current in the development of binaural temporal precision.
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DOI：
10.1523/jneurosci.3882-11.2012
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发表时间：
2012-02-22
期刊：
影响因子：
--
通讯作者：
Golding NL
中科院分区：
文献类型：
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作者：
Khurana S;Liu Z;Lewis AS;Rosa K;Chetkovich D;Golding NL
在大脑的感觉回路中，电压门控离子通道的表达和调节的发育变化是常见的，但这种变化往往难以分配到明确的功能作用。我们已经探讨了这个问题，在双耳神经元的内侧上级橄榄（MSO），其时间精度在检测双耳输入的一致性决定了方位角的声音定位的分辨率。我们发现，在听觉的第一周，在沙鼠的MSO主神经元中，超极化激活电流（Ih）逐渐经历了最大电导的13倍增加，>10倍的动力学加速，最令人惊讶的是，在激活的电压依赖性中有30 mV的去极化偏移。这一时期与超极化和环核苷酸门控（HCN）通道亚基HCN 1，2和4在MSO的上调，但只有HCN 1和4强烈表达的主要神经元。在电生理学成熟的MSO神经元（>P18）的有核斑中记录的Ih表现出与听力发作前全细胞记录中发现的Ih几乎相同的动力学和激活范围。这些结果表明，Ih在MSO神经元的发育变化可以解释主要是由调制从扩散的细胞内因素，而不是通道亚基组成的变化。Ih的异常大的调制变化，以及突触特性的改进，将编码策略从求和和整合转变为已知的声音定位线索传输所需的亚毫秒重合检测。
In sensory circuits of the brain, developmental changes in the expression and modulation of voltage-gated ion channels are a common occurrence, but such changes are often difficult to assign to clear functional roles. We have explored this issue in the binaural neurons of the medial superior olive (MSO), whose temporal precision in detecting the coincidence of binaural inputs dictates the resolution of azimuthal sound localization. We show that in MSO principal neurons of gerbils during the first week of hearing, a hyperpolarization-activated current (Ih) progressively undergoes a 13-fold increase in maximal conductance, >10-fold acceleration of kinetics, and most surprisingly, a 30 mV depolarizing shift in the voltage dependence of activation. This period is associated with an upregulation of the hyperpolarization and cyclic nucleotide-gated (HCN) channel subunits HCN1, 2, and 4 in the MSO, but only HCN1 and 4 were expressed strongly in principal neurons. Ih recorded in nucleated patches from electrophysiologically mature MSO neurons (>P18) exhibited kinetics and an activation range nearly identical to Ih found in whole-cell recordings prior to hearing onset. These results indicate that the developmental changes in Ih in MSO neurons can be explained predominantly by modulation from diffusible intracellular factors, and not changes in channel subunit composition. The exceptionally large modulatory changes in Ih, together with refinements in synaptic properties transform the coding strategy from one of summation and integration to the submillisecond coincidence detection known to be required for transmission of sound localization cues.