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Mitf Links Neuronal Activity and Long-Term Homeostatic Intrinsic Plasticity

Mitf Links Neuronal Activity and Long-Term Homeostatic Intrinsic Plasticity

Title: Mitf Links Neuronal Activity and Long-Term Homeostatic Intrinsic Plasticity
Author: Atacho, Diahann A. M.
Reynisson, Hallur
Pétursdóttir, Anna Þóra
Eysteinsson, Thor   orcid.org/0000-0002-9748-5854
Steingrimsson, Eirikur   orcid.org/0000-0001-5826-7486
Petersen, Petur Henry   orcid.org/0000-0001-6622-3002
Date: 2020-03
Language: English
Scope: ENEURO.0412-19.2020
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Lífvísindasetur (HÍ)
Biomedical Center (UI)
Læknadeild (HÍ)
Faculty of Medicine (UI)
Series: Eneuro;7(2)
ISSN: 2373-2822
DOI: 10.1523/ENEURO.0412-19.2020
Subject: Genetics; Hyperactivity; Intrinsic plasticity; Kcnd3; Potassium channel; Transcription; Erfðafræði; Gen; Taugafrumur
URI: https://hdl.handle.net/20.500.11815/1933

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Atacho, D. A. M., Reynisson, H., Petursdottir, A. T., Eysteinsson, T., Steingrimsson, E., & Petersen, P. H. (2020). Mitf Links Neuronal Activity and Long-Term Homeostatic Intrinsic Plasticity. 7(2), ENEURO.0412-0419.2020. doi:10.1523/ENEURO.0412-19.2020 %J eneuro


Neuroplasticity forms the basis for neuronal circuit complexity and differences between otherwise similar circuits. We show that the microphthalmia-associated transcription factor (Mitf) plays a central role in intrinsic plasticity of olfactory bulb (OB) projection neurons. Mitral and tufted (M/T) neurons from Mitf mutant mice are hyperexcitable, have a reduced A-type potassium current (IA) and 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 and the MITF protein activates expression from Kcnd3 regulatory elements. Moreover, Mitf mutant mice have changes in olfactory habituation and have increased habituation for an odorant 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 and links neuronal activity, transcriptional changes and neuronal function.


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