Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (2): 364-367.doi: 10.4103/1673-5374.346544

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Nicotinic acetylcholine signaling is required for motor learning but not for rehabilitation from spinal cord injury

Yue Li1, †, Edmund R. Hollis II1, 2, *   

  1. 1Burke Neurological Institute, White Plains, NY, USA; 2Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA
  • Online:2023-02-15 Published:2022-08-08
  • Contact: Edmund R. Hollis II, PhD, edh3001@med.cornell.edu.
  • Supported by:
    This study was supported by the Burke Foundation and the National Institutes of Health Common Fund, No. DP2 NS106663 (to ERH); the New York State Department of Health Spinal Cord Injury Research Board Postdoctoral Fellowship, No. C32633GG (to YL).

Abstract: Therapeutic intervention for spinal cord injury is limited, with many approaches relying on strengthening the remaining substrate and driving recovery through rehabilitative training. As compared with learning novel compensatory strategies, rehabilitation focuses on restoring movements lost to injury. Whether rehabilitation of previously learned movements after spinal cord injury requires the molecular mechanisms of motor learning, or if it engages previously trained motor circuits without requiring novel learning remains an open question. In this study, mice were randomly assigned to receive intraperitoneal injection with the pan-nicotinic, non-competitive antagonist mecamylamine and the nicotinic α7 subunit selective antagonist methyllycaconitine citrate salt or vehicle (normal saline) prior to motor learning assays, then randomly reassigned after motor learning for rehabilitation study post-injury. Cervical spinal cord dorsal column lesion was used as a model of incomplete injury. Results of this study showed that nicotinic acetylcholine signaling was required for motor learning of the single pellet-reaching task but it was dispensable for the rehabilitation of the same task after injury. Our findings indicate that critical differences exist between the molecular mechanisms supporting compensatory motor learning strategies and the restoration of behavior lost to spinal cord injury.

Key words: acetylcholine, basal forebrain, corticospinal tract, dorsal column lesion, mecamylamine, methyllycaconitine, motor control, rehabilitation, rotarod, single pellet-reaching task