Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2019
Erindi/veggspjald / Talk/poster V77
Höfundar / Authors: Diahann Atacho, Hallur Reynisson, Þór Eysteinsson, Eiríkur Steingrímsson, Pétur Henry Petersen
Starfsvettvangur / Affiliations: Lífvísindasetur Háskóla Íslands
Kynnir / Presenter: Petur Henry Petersen
The Microphthalmia associated transcription factor (MITF) is a basic helix-loop-helix-leucine zipper transcription factor essential for the development of melanocytes and mast cells. Mitf is also expressed in the glutamatergic projection neurons of the mouse olfactory bulb. Mitf has been shown in melanocytes to be regulated by glutamate signaling. As the nervous system itself is shaped and regulated by glutamate signaling, we determined whether MITF takes part in activity-induced responses at the transcriptional level. Using the Mitfmi-vga9 mouse model, we have determined that lack of Mitf leads to an increase in the ability of the Mitfmi-vga9 mouse to distinguish between odors, while its capacity to detect odor is similar to the wild type mice. However, the ability of the mutant mice to adapt to odors over a period of hours is changed. We have identified tentative target genes of MITF in the projection neurons of the OB, including the potassium channels subunit Kcnd3, which is important for type A potassium current. Expression of both Mitf and Kcnd3 is activity-dependent and expression of Kcnd3 is Mitf dependent. MITF binds to a strong enhancer of the Kcnd3 gene, suggesting that MITF regulates Kcnd3 expression directly. A decrease in Type A- potassium current in Mitfmi-vga9 mouse M/T neurons is also observed, and a concomitant increase in neuronal activity of the M/T neurons of the Mitfmi-vga9 mouse. Other putative target genes of MITF in OB projection neurons, suggest a general role of MITF as a negative regulator of neuronal activity. We propose a model, where MITF regulates intrinsic plasticity in the olfactory bulb projection neurons. The role of MITF in neuronal homeostasis following activity suggests that MITF plays a major role in long-term selective olfactory habituation and homestatic plasticity.