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Synaptic mechanisms underlying modulation of locomotor-related motoneuron output by premotor cholinergic interneurons.

Filipe NascimentoMatthew James BroadheadEfstathia TetringaEirini TsapeLaskaro ZagoraiouGareth Brian Miles
Published in: eLife (2020)
Spinal motor networks are formed by diverse populations of interneurons that set the strength and rhythmicity of behaviors such as locomotion. A small cluster of cholinergic interneurons, expressing the transcription factor Pitx2, modulates the intensity of muscle activation via 'C-bouton' inputs to motoneurons. However, the synaptic mechanisms underlying this neuromodulation remain unclear. Here, we confirm in mice that Pitx2+ interneurons are active during fictive locomotion and that their chemogenetic inhibition reduces the amplitude of motor output. Furthermore, after genetic ablation of cholinergic Pitx2+ interneurons, M2 receptor-dependent regulation of the intensity of locomotor output is lost. Conversely, chemogenetic stimulation of Pitx2+ interneurons leads to activation of M2 receptors on motoneurons, regulation of Kv2.1 channels and greater motoneuron output due to an increase in the inter-spike afterhyperpolarization and a reduction in spike half-width. Our findings elucidate synaptic mechanisms by which cholinergic spinal interneurons modulate the final common pathway for motor output.
Keyphrases
  • transcription factor
  • spinal cord injury
  • prefrontal cortex
  • magnetic resonance imaging
  • metabolic syndrome
  • dna methylation
  • genome wide