Mitf links neuronal activity and long-term homeostatic intrinsic plasticity

Diahann A. M. Atacho, Hallur Reynisson, Anna Þóra Pétursdóttir, Thor Eysteinsson, Eiríkur Steingrímsson, Pétur Henry Petersen

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Mar 08, 2019
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Received Date: 18th February 19

Neuroplasticity forms the basis for neuronal circuit complexity and can determine differences between otherwise similar circuits. Although synaptic plasticity is fairly well characterized, much less is known about the molecular mechanisms underlying intrinsic plasticity, especially its transcriptional regulation. We show that the Microphthalmia-associated transcription factor (Mitf), best known as the master regulator of melanocytic cell fate and differentiation, plays a central role in homeostatic intrinsic plasticity of olfactory bulb (OB) projection neurons. Mitral and tufted (M/T) neurons from Mitf mutant mice are hyperexcitable due to reduced Type-A potassium current (IA) and they exhibit reduced expression of Kcnd3, which encodes a potassium voltage-gated channel subunit (Kv4.3) important for generating the IA. Furthermore, expression of the Mitf and Kcnd3 genes is activity-dependent in OB projection neurons, The MITF protein binds to and activates expression from Kcnd3 regulatory elements. Activity can therefore affect Kcnd3 expression directly via MITF. Moreover, Mitf mutant mice have changes in olfactory habituation and have increased habitutation for an odourant following long-term exposure, indicating that regulation of Kcnd3 is pivotal for long-term olfactory adaptation. Our findings show that Mitf acts as a direct regulator of intrinsic homeostatic feedback, plays a key role in olfactory adaptation and links neuronal activity, transcriptional changes and neuronal function.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.


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