Journal
NEURON
Volume 46, Issue 1, Pages 37-49Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2005.02.022
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Funding
- FIC NIH HHS [TW005563] Funding Source: Medline
- NCI NIH HHS [P30 CA14195, T32 CA09370] Funding Source: Medline
- NIGMS NIH HHS [5 T32 GM07198] Funding Source: Medline
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Rhythmic limb movements are controlled by pattern-generating neurons within the ventral spinal cord, but little is known about how these locomotor circuits are assembled during development. At early stages of embryogenesis, motor neurons are spontaneously active, releasing acetylcholine that triggers the depolarization of adjacent cells in the spinal cord. To investigate whether acetylcholine-driven activity is required for assembly of the central pattern-generating (CPG) circuit, we studied mice lacking the choline acetyltransferase (ChAT) enzyme. Our studies show that a rhythmically active spinal circuit forms in ChAT mutants, but the duration of each cycle period is elongated, and right-left and flexor-extensor coordination are abnormal. In contrast, blocking acetylcholine receptors after the locomotor network is wired does not affect right-left or flexor-extensor coordination. These findings suggest that the cholinergic neurotransmitter pathway is involved in configuring the CPG during a transient period of development.
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