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

Panagiotis E Eleftheriadis, Konstantinos Pothakos, Simon A. Sharples, Panagiota E Apostolou, Maria Mina, Efstathia Tetringa, Eirini Tsape, Gareth B. Miles, Laskaro Zagoraiou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Article numbere2300348120
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number39
Early online date21 Sept 2023
Publication statusPublished - 26 Sept 2023


  • Motor control
  • Acetylcholine
  • Cocaine and amphetamine regulated transcript
  • Spinal cord
  • C boutons


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