title: Cholinergic input is required during embryonic development to mediate proper assembly of spinal locomotor circuits.
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.
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Myers
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Lewcock
authors.forename: M Gartz
authors.initials: MG
authors.lastname: Hanson
authors.forename: Simon
authors.initials: S
authors.lastname: Gosgnach
authors.forename: James B
authors.initials: JB
authors.lastname: Aimone
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
authors.forename: Kuo-Fen
authors.initials: KF
authors.lastname: Lee
authors.forename: Lynn T
authors.initials: LT
authors.lastname: Landmesser
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Pfaff
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001259:Ataxia / Q000209:etiology; D002795:Choline O-Acetyltransferase / Q000172:deficiency*; D004594:Electrophysiology; D004622:Embryo, Mammalian; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000502:physiology; D009046:Motor Neurons / Q000378:metabolism*; D009434:Neural Pathways / Q000196:embryology* / Q000201:enzymology; D009924:Organ Culture Techniques; D013116:Spinal Cord / Q000196:embryology*
chemical_list: D002795:Choline O-Acetyltransferase; D000109:Acetylcholine