Department of Anatomy, BioMedical Center, Faculty of Medicine.
Department of Biochemistry and Molecular Biology, BioMedical Center, Faculty of Medicine.
eNeuro. 2020 Apr 21;7(2). doi: 10.1523/ENEURO.0412-19.2020. Print 2020 Mar/Apr.
Neuroplasticity forms the basis for neuronal circuit complexity and differences between otherwise similar circuits. We show that the microphthalmia-associated transcription factor () plays a central role in intrinsic plasticity of olfactory bulb (OB) projection neurons. Mitral and tufted (M/T) neurons from mutant mice are hyperexcitable, have a reduced A-type potassium current (I) and exhibit reduced expression of , which encodes a potassium voltage-gated channel subunit (Kv4.3) important for generating the I Furthermore, expression of the and genes is activity dependent in OB projection neurons and the MITF protein activates expression from regulatory elements. Moreover, mutant mice have changes in olfactory habituation and have increased habituation for an odorant following long-term exposure, indicating that regulation of is pivotal for long-term olfactory adaptation. Our findings show that acts as a direct regulator of intrinsic homeostatic feedback and links neuronal activity, transcriptional changes and neuronal function.
神经可塑性是神经元回路复杂性和相似回路之间差异的基础。我们表明小眼畸形相关转录因子（MITF）在嗅球（OB）投射神经元的内在可塑性中发挥核心作用。来自突变小鼠的僧帽细胞和丛状细胞（M/T）神经元兴奋性过高，A 型钾电流（I）减少，并表现出编码钾电压门控通道亚基（Kv4.3）的减少，该亚基对于产生 I 很重要。此外，OB 投射神经元中 和 基因的表达依赖于活动，MITF 蛋白激活 调节元件的表达。此外，突变小鼠的嗅觉习惯化发生变化，并且在长期暴露后对气味的习惯化增加，表明 调节对于长期嗅觉适应至关重要。我们的发现表明，MITF 作为内在动态平衡反馈的直接调节剂，将神经元活动、转录变化和神经元功能联系起来。
