Sana Gadiwalla, Fatich Mechmet and Petur Henry Petersen
Introduction. Neuronal plasticity is crucial for learning and memory and pivotal in neurological disorders like epilepsy and neurodegeneration. Intrinsic to plasticity is neuronal activity which plays a key role in the maintenance of neuronal circuits. We have shown that the microphthalmia-associated transcription factor (Mitf) is key in regulating neuronal activity in projection neurons (PNs) of the murine olfactory bulb (OB) supported by hyperactive phenotypes in primary cell models. As PNs have a direct impact on sensory processing disrupting their behavior leads to olfactory deficits; indeed, Mitf constitutive mutants have deficits in long term olfactory adaptation. Methods. To visualize discrepancies in neuronal activity at the level of circuitry, constitutive Mitf knockout mice were presented with acute odor enrichment. We performed RNAseq to identify activity dependent target genes and followed up with RNA in-situ hybridization, immunohistochemistry and real-time qPCR. Results. Focusing on immediate early genes, preliminary results from RNAseq data when compared to wild type controls, demonstrate that Mitf mutants do not respond correctly to activity induction in a cell-type specific manner. Conclusions. These results confirm functional defects in olfaction and offer insights into Mitf’s role in the transcriptional regulation of neuronal activity.
