Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025

Erindi/veggspjald / Talk/poster V42

Modulation of bulbar activity in a mouse model of impaired intrinsic excitability

Höfundar / Authors: S. Gadiwalla(1,2), E. Galliano(2), P.H. Petersen(1)

Starfsvettvangur / Affiliations: 1. Lífvísindasvið Læknadeildar Háskóla Íslands 2. Cambridge Háskóli

Kynnir / Presenter: Sana Gadiwalla

Intrinsic excitability regulation is a critical yet understudied aspect of adaptive neuronal plasticity, essential for maintaining stable neural activity in response to perturbations. Uncovering the molecular regulators of intrinsic excitability modulation is challenging due to its dynamic, cell-specific nature and the interplay between synaptic and intrinsic mechanisms. In the olfactory bulb headway has been made by discovering that the microphthalmia-associated transcription factor (Mitf) is specifically expressed in projection neurons (PN, mitral and tufted cells) and that in primary culture of knock-out mutant (MT) mice, the loss of Mitf results in hyperactive PNs. Using immunohistochemistry and cell whole cell patch clamp in acute slices this project assessed the role of Mitf in the transcriptional control of intrinsic excitability in bulbar PNs in a model where circuitry is maintained. Compared to WT controls, Mitf mutants PNs have shorter axon initial segments (WT 25.42±0.4μm; MT 23.05±0.7μm; t-test p=0.004) that are closer to the soma (WT 4.7±0.2μm; MT 3.7±0.2μm; t-test p<0.001). These structural changes are alignment with the physiological hyperexcitability of MT PNs. in current clamp, MTs fired more action potentials (WT 32.1±5.4; MT 51.0±4.1; Mann-Whitney p=0.013) with shorter latency to fire (WT 23.6±3.1ms; MT 16.9±0.2ms; Mann-Whitney p=0.029). Moreover, after 30 minutes of home-cage exposure to 8 odours before slice preparation, Mitf MTs showed altered gain con