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

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 pathogene...

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Vydáno v:bioRxiv
Hlavní autoři: Antonucci, Stefano, Caron, Guillaume, Dikwella, Natalie, Krishnamurty, Sruthi Sankari, Harster, Anthony, Zarrin, Hina, Tahanis, Aboud, Heuvel, Florian Olde, Danner, Simon M, Ludolph, Albert C, Grycz, Kamil, Bączyk, Marcin, Zytnicki, Daniel, Roselli, Francesco
Médium: Journal Article Paper
Jazyk:angličtina
Vydáno: United States Cold Spring Harbor Laboratory Press 20.12.2024
Cold Spring Harbor Laboratory
Vydání:3.1
Témata:
Adrenergic receptors
Amyotrophic lateral sclerosis
Down-regulation
Electrical properties
Excitability
Feedback
Motor neurons
Neural networks
Neuromodulation
Neuroscience
Receptor mechanisms
Superoxide dismutase
β-adrenergic neuromodulation
Amyotrophic Lateral Sclerosis
homeostatic feedbacks
in vivo intracellular electrophysiology
Spinal motoneurons
transcriptomics
GPCR
channelome
ISSN:2692-8205, 2692-8205
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Shrnutí: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 β2 and β3- 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 firing and excitability properties of MNs. 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.
Bibliografie:SourceType-Working Papers-1
ObjectType-Working Paper/Pre-Print-1
content type line 50
Competing Interest Statement: The authors have declared no competing interest.
ISSN:2692-8205
2692-8205
DOI:10.1101/2024.03.25.586570