“Peptidergic modulation of motor neuron output via CART signaling at C bouton synapses”

Abstract

The intensity of muscle contraction, and therefore movement vigour, needs to be adaptable to enable complex motor behaviors. This can be achieved by adjusting the properties of motor neurons, which form the final common pathway for all motor output from the central nervous system. Here we identify novel roles for a neuropeptide, Cocaine and Amphetamine Regulated Transcript (CART), in the control of movement vigour. We reveal distinct, but parallel mechanisms by which CART and acetylcholine, both released at C bouton synapses on motor neurons, selectively amplify the output of subtypes of motor neurons that are recruited during intense movement. We find that mice with broad genetic deletion of CART or selective elimination of acetylcholine from C boutons exhibit deficits in behavioral tasks that require higher levels of motor output. Overall, these data uncover novel spinal modulatory mechanisms that control movement vigour to support movements that require a high degree of muscle force.

M‐type potassium currents differentially affect activation of motoneuron subtypes and tune recruitment gain

“…These results establish roles for voltage‐gated ion channels in the differential control of motoneuron recruitment, which is important because many of these channels are well known to be targeted by multiple neuromodulatory inputs. Indeed, emerging evidence points toward differential control of motoneuron subtypes, through yet unresolved mechanisms (Bertuzzi & Ampatzis, 2018; Jha & Thirumalai, 2020; Eleftheriadis et al., 2023). M‐type potassium currents were initially described based on the inhibitory influence of muscarine on these channels (Brown & Adams, 1980; Wang et al., 1998).…”

“…While cholinergic pathways are likely to modulate M‐currents in turtle motoneurons (Alaburda et al., 2002), they do not contribute to cholinergic modulation of hypoglossal motoneurons (Ireland et al., 2012). Although not tested directly in mouse lumbar motoneurons, pharmacological activation of muscarinic receptors in fast motoneurons produces a very different complement of changes in intrinsic properties compared to manipulating KCNQ channels (Miles et al., 2007; Nascimento et al., 2019; Eleftheriadis et al., 2023). On the other hand, 5‐HT fibres have been reported at the AIS (Deardorff et al., 2021) where KCNQ channels are clustered (Verneuil et al., 2020).…”

“…Asterisks denote significance: * P <0.05, * * P < 0.01. [Colour figure can be viewed at wileyonlinelibrary.com] Ampatzis, 2018;Jha & Thirumalai, 2020;Eleftheriadis…”

M-type potassium currents differentially affect activation of motoneuron subtypes and tune recruitment gain

“…Asterisks denote significance: * P <0.05, * * P < 0.01. Jha & Thirumalai, 2020;Eleftheriadis et al, 2023). M-type potassium currents were initially described based on the inhibitory influence of muscarine on these channels (Brown & Adams, 1980;Wang et al, 1998).…”

“…While cholinergic pathways are likely to modulate M-currents in turtle motoneurons (Alaburda et al, 2002), they do not contribute to cholinergic modulation of hypoglossal motoneurons (Ireland et al, 2012). Although not tested directly in mouse lumbar motoneurons, pharmacological activation of muscarinic receptors in fast motoneurons produces a very different complement of changes in intrinsic properties compared to manipulating KCNQ channels (Miles et al, 2007;Nascimento et al, 2019;Eleftheriadis et al, 2023). On the other hand, 5-HT fibres have been reported at the AIS (Deardorff et al, 2021) where KCNQ channels are clustered (Verneuil et al, 2020).…”