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PMID:15820692

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Citation

Myers, CP, Lewcock, JW, Hanson, MG, Gosgnach, S, Aimone, JB, Gage, FH, Lee, KF, Landmesser, LT and Pfaff, SL (2005) Cholinergic input is required during embryonic development to mediate proper assembly of spinal locomotor circuits. Neuron 46:37-49

Abstract

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.

Links

PubMed Online version:10.1016/j.neuron.2005.02.022

Keywords

Acetylcholine/metabolism; Action Potentials/physiology; Animals; Ataxia/etiology; Choline O-Acetyltransferase/deficiency; Electrophysiology; Embryo, Mammalian; Immunohistochemistry; In Situ Hybridization; Mice; Mice, Mutant Strains; Motor Activity/physiology; Motor Neurons/metabolism; Neural Pathways/embryology; Neural Pathways/enzymology; Organ Culture Techniques; Spinal Cord/embryology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CLAT

acts_upstream_of_or_within

GO:0007628: adult walking behavior

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2450310

P

Seeded From UniProt

complete

MOUSE:CLAT

acts_upstream_of_or_within

GO:0007622: rhythmic behavior

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2450310

P

Seeded From UniProt

complete

MOUSE:CLAT

acts_upstream_of_or_within

GO:0043179: rhythmic excitation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2450310

P

Seeded From UniProt

complete

See also

References

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