Mitf Links Neuronal Activity and Long-Term Homeostatic Intrinsic Plasticity.

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.