V1 and V2b Interneurons Secure the Alternating Flexor-Extensor Motor Activity Mice Require for Limbed Locomotion

• Type of Material: Article
• Authors: Jingming Zhang, Salk Institute for Biological Studies; Guillermo M. Lanuza, Salk Institute for Biological Studies; Olivier Britz, Salk Institute for Biological Studies; Zhi Wang, Tufts University; Valerie C. Siembab, Wright State University; Ying Zhang, Emory University; Tomoka Velasquez, Salk Institute for Biological Studies; Francisco Alvarez, Emory University; Eric Frank, Tufts University; Martyn Goulding, Salk Institute for Biological Studies
• Language: English
• Date: 2014-04-02
• Publisher: Elsevier (Cell Press): 12 month embargo
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.neuron.2014.02.013
• Title of Journal or Parent Work: Neuron
• ISSN: 0896-6273
• Volume: 82
• Issue: 1
• Start Page: 138
• End Page: 150
• Grant/Funding Information: This research was supported by grants from the National Institutes of Health (R37-NS037075, P01-NS031249, R01-NS047357); the Human Frontier Science Program; and the Christopher and Dana Reeve Foundation.; GL was supported by an HFSP postdoctoral fellowship.
• Keywords: RECIPROCAL IA INHIBITION; Science & Technology; NEONATAL-RAT; GREEN FLUORESCENT PROTEIN; SYNAPTIC DRIVE; Neurosciences; NEURONS; MOTONEURONS; SPINAL-CORD; NETWORKS; Neurosciences & Neurology; LOCALIZATION; V2-DERIVED INTERNEURONS; Life Sciences & Biomedicine
• Research Categories: Biology, Neuroscience; Biology, Physiology

Abstract

Reciprocal activation of flexor and extensor muscles constitutes the fundamental mechanism that tetrapod vertebrates use for locomotion and limb-driven reflex behaviors. This aspect of motor coordination is controlled by inhibitory neurons in the spinal cord; however, the identity of the spinal interneurons that serve this function is not known. Here, we show that the production of an alternating flexor-extensor motor rhythm depends on the composite activities of two classes of ventrally located inhibitory neurons, V1 and V2b interneurons (INs). Abrogating V1 and V2b IN-derived neurotransmission in the isolated spinal cord results in a synchronous pattern of L2 flexor-related and L5 extensor-related locomotor activity. Mice lacking V1 and V2b inhibition are unable to articulate their limb joints and display marked deficits in limb-driven reflex movements. Taken together, these findings identify V1- and V2b-derived neurons as the core interneuronal components of the limb central pattern generator (CPG) that coordinate flexor-extensor motor activity.