Molecular Neurophysiology and Biophysics Unit, Program in Development Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Neurosci. 2012 Oct 10;32(41):14427-32. doi: 10.1523/JNEUROSCI.2373-12.2012.
Neuronal activity is critical for the formation and modification of neural circuits during brain development. In hippocampal CA1 pyramidal dendrites, A-type voltage-gated K(+) currents, formed primarily by Kv4.2 subunits, control excitability. Here we used Kv4.2 knock-out (Kv4.2-KO) mice along with acute in vivo expression of Kv4.2 or its dominant-negative pore mutant to examine the role of Kv4.2 in the development of CA1 synapses. We found that Kv4.2 expression induces synaptic maturation in juvenile WT mice and rescues developmentally delayed synapses in adult Kv4.2-KO mice. In addition, we show that NMDAR subunit composition can be reverted back to the juvenile form in WT adult synapses by functionally downregulating Kv4.2 levels. These results suggest that Kv4.2 regulation of excitability determines synaptic maturation state, which can be bidirectionally adjusted into adulthood.
神经元活动对于大脑发育过程中神经回路的形成和修饰至关重要。在海马 CA1 锥体树突中，由 Kv4.2 亚基主要构成的 A 型电压门控 K(+)电流控制兴奋性。在这里，我们使用 Kv4.2 敲除 (Kv4.2-KO) 小鼠，以及 Kv4.2 的急性体内表达或其显性失活孔突变体，来研究 Kv4.2 在 CA1 突触发育中的作用。我们发现，Kv4.2 的表达可诱导幼年 WT 小鼠的突触成熟，并挽救成年 Kv4.2-KO 小鼠发育延迟的突触。此外，我们还表明，通过功能下调 Kv4.2 水平，WT 成年突触中的 NMDAR 亚基组成可以逆转回幼年形式。这些结果表明，Kv4.2 对兴奋性的调节决定了突触成熟状态，这种状态可以在成年期进行双向调节。
