Netrin-1-dependent spinal interneuron subtypes are required for the formation of left-right alternating locomotor circuitry

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

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.

Details

Original languageEnglish
Pages (from-to)15642-9
Number of pages8
JournalJournal of Neuroscience
Volume29
Issue number50
Publication statusPublished - 16 Dec 2009
Peer-reviewedYes

External IDs

PubMedCentral PMC6666172
Scopus 72449144159
ORCID /0000-0002-3188-8431/work/142251775

Keywords

Keywords

  • Animals, Animals, Newborn, Functional Laterality/physiology, Interneurons/cytology, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Motor Activity/physiology, Nerve Growth Factors/physiology, Nerve Net/cytology, Netrin-1, Psychomotor Performance/physiology, Spinal Cord/cytology, Tumor Suppressor Proteins/physiology