title: Netrin-1-dependent spinal interneuron subtypes are required for the formation of left-right alternating locomotor circuitry.
abstract: Neuronal circuits in the spinal cord that produce the rhythmic and coordinated activities necessary for limb movements are referred to as locomotor central pattern generators (CPGs). The identities and preceding development of neurons essential for coordination between left and right limbs are not yet known. We show that the ventral floor plate chemoattractant Netrin-1 preferentially guides dorsally originating subtypes of commissural interneurons, the majority of which are inhibitory. In contrast, the excitatory and ventralmost V3 subtype of interneurons have a normal number of commissural fibers in Netrin-1 mutant mice, thus being entirely independent of Netrin-1-mediated attraction. This selective loss of commissural fibers in Netrin-1 mutant mice resulted in an abnormal circuitry manifested by a complete switch from alternating to synchronous fictive locomotor activity suggesting that the most ventral-originating excitatory commissural interneurons are an important component of a left-right synchrony circuit in the locomotor CPG. Thus, during development, Netrin-1 plays a critical role for the establishment of a functional balanced CPG.
authors.affiliation: Department of Neuroscience, Uppsala University, 751 24 Uppsala, Sweden.
authors.forename: Nadine
authors.initials: N
authors.lastname: Rabe
authors.forename: Henrik
authors.initials: H
authors.lastname: Gezelius
authors.forename: Anna
authors.initials: A
authors.lastname: Vallstedt
authors.forename: Fatima
authors.initials: F
authors.lastname: Memic
authors.forename: Klas
authors.initials: K
authors.lastname: Kullander
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D007839:Functional Laterality / Q000502:physiology*; D007395:Interneurons / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000502:physiology*; D009414:Nerve Growth Factors / Q000502:physiology*; D009415:Nerve Net / Q000166:cytology / Q000502:physiology*; D000075388:Netrin-1; D011597:Psychomotor Performance / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1