ArticleScientific reports2019
Balanced cholinergic modulation of spinal locomotor circuits via M2 and M3 muscarinic receptors.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- From pharmacophore predictions to pharmaceutical possibilities: an integrated approach to screen MMolecular diversity · 2026Article
- Synergistic mechanisms of medullary cholinergic-serotonergic pathway interactions in regulating neuronal excitability and locomotor activities.Communications biology · 2025Article
- Synaptopathy in the TDP-43ΔNLS Mouse Model of Sporadic Amyotrophic Lateral Sclerosis.The European journal of neuroscience · 2025Article
- Episodic rhythmicity is generated by a distributed neural network in the developing mammalian spinal cord.iScience · 2025Article
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- Multiple cholinergic receptor subtypes coordinate dual modulation of acetylcholine on anterior and posterior paraventricular thalamic neurons.Journal of neurochemistry · 2024Article
- Peptidergic modulation of motor neuron output via CART signaling at C bouton synapses.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Cholinergic Modulation of Locomotor Circuits in Vertebrates.International journal of molecular sciences · 2022Review
- Preclinical Evidence for the Role of Botulinum Neurotoxin A (BoNT/A) in the Treatment of Peripheral Nerve Injury.Microorganisms · 2022Review
- UtilizingBiochemistry and biophysics reports · 2022Article
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- Acetylcholine and spinal locomotor networks: The insider.Physiological reports · 2021Review
- A dynamic role for dopamine receptors in the control of mammalian spinal networks.Scientific reports · 2020Article
- Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuromodulation ensures that neural circuits produce output that is flexible whilst remaining within an optimal operational range. The neuromodulator acetylcholine is released during locomotion to regulate spinal motor circuits. However, the range of receptors and downstream mechanisms by which acetylcholine acts have yet to be fully elucidated. We therefore investigated metabotropic acetylcholine receptor-mediated modulation by using isolated spinal cord preparations from neonatal mice in which locomotor-related output can be induced pharmacologically. We report that M2 receptor blockade decreases the frequency and amplitude of locomotor-related activity, whilst reducing its variability. In contrast, M3 receptor blockade destabilizes locomotor-related bursting. Motoneuron recordings from spinal cord slices revealed that activation of M2 receptors induces an outward current, decreases rheobase, reduces the medium afterhyperpolarization, shortens spike duration and decreases synaptic inputs. In contrast, M3 receptor activation elicits an inward current, increases rheobase, extends action potential duration and increases synaptic inputs. Analysis of miniature postsynaptic currents support that M2 and M3 receptors modulate synaptic transmission via different mechanisms. In summary, we demonstrate that M2 and M3 receptors have opposing modulatory actions on locomotor circuit output, likely reflecting contrasting cellular mechanisms of action. Thus, intraspinal cholinergic systems mediate balanced, multimodal control of spinal motor output.
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