title: In vivo activation of channelrhodopsin-2 reveals that normal patterns of spontaneous activity are required for motoneuron guidance and maintenance of guidance molecules.
abstract: Spontaneous, highly rhythmic episodes of propagating bursting activity are present early during the development of chick and mouse spinal cords. Acetylcholine, and GABA and glycine, which are both excitatory at this stage, provide the excitatory drive. It was previously shown that a moderate decrease in the frequency of bursting activity, caused by in ovo application of the GABA(A) receptor blocker, picrotoxin, resulted in motoneurons making dorsal-ventral (D-V) pathfinding errors in the limb and in the altered expression of guidance molecules associated with this decision. To distinguish whether the pathfinding errors were caused by perturbation of the normal frequency of bursting activity or interference with GABA(A) receptor signaling, chick embryos were chronically treated in ovo with picrotoxin to block GABA(A) receptors, while light activation by channelrhodopsin-2 was used to restore bursting activity to the control frequency. The restoration of normal patterns of neural activity in the presence of picrotoxin prevented the D-V pathfinding errors in the limb and maintained the normal expression levels of EphA4, EphB1, and polysialic acid on neural cell adhesion molecule, three molecules previously shown to be necessary for this pathfinding choice. These observations demonstrate that developing spinal motor circuits are highly sensitive to the precise frequency and pattern of spontaneous activity, and that any drugs that alter this activity could result in developmental defects.
authors.affiliation: Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4975, USA.
authors.forename: Ksenia V
authors.initials: KV
authors.lastname: Kastanenka
authors.forename: Lynn T
authors.initials: LT
authors.lastname: Landmesser
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D002642:Chick Embryo; D018756:GABA Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000378:metabolism*; D012243:Rhodopsin / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D018756:GABA Antagonists; D009419:Nerve Tissue Proteins; D010852:Picrotoxin; D011963:Receptors, GABA-A; D012243:Rhodopsin