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Spinal motoneuron excitability is homeostatically-regulated through β-adrenergic neuromodulation in wild-type and presymptomatic SOD1 mice
Journal article   Open access   Peer reviewed

Spinal motoneuron excitability is homeostatically-regulated through β-adrenergic neuromodulation in wild-type and presymptomatic SOD1 mice

Stefano Antonucci, Guillaume Caron, Natalie Dikwella, Sruthi Sankari Krishnamurth, Anthony Harster, Bartosz Wasicki, Hina Zarrin, Aboud Tahani, Florian olde Heuvel, Simon M Danner, …
Progress in neurobiology, v 260, 102905
01 Mar 2026
DOI: https://doi.org/10.1016/j.pneurobio.2026.102905
PMID: 41812870
Featured in Collection :   Drexel's Newest Publications
url
https://doi.org/10.1016/j.pneurobio.2026.102905View
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Abstract

beta-adrenergic neuromodulation Homeostatic regulation G protein-coupled receptors Channelome Amyotrophic Lateral Sclerosis Transcriptomics in vivo intracellular electrophysiology
Homeostatic feedback loops are essential to stabilize the activity of neurons and neuronal networks. It has been hypothesized that, in the context of Amyotrophic Lateral Sclerosis (ALS), an excessive gain in feedback loops might hyper- or hypo-excite motoneurons (MNs) and contribute to the pathogenesis. Here, we investigated how the neuromodulation of MN intrinsic properties is homeostatically controlled in presymptomatic adult SOD1(G93A) mice and in the age-matched control WT mice. First, we determined that Adrb2 and Adrb3 adrenergic receptors, which are Gs-coupled receptors and subject to tight and robust feedback loops, are specifically expressed in spinal MNs of both SOD1 and WT mice at P45. We then demonstrated that these receptors elicit a so-far overlooked neuromodulation of the electrical properties of MNs, in particular the frequency-current gain, a crucial determinant of excitability. These electrical properties are homeostatically regulated following receptor engagement, which triggers ion channel transcriptional changes and downregulates those receptors. These homeostatic feedbacks are not dysregulated in presymptomatic SOD1 mice, and they set the MN excitability upon β-adrenergic neuromodulation.

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