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

Abstract

SUMMARY The 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.

Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus

“…In the mouse, V1 INs play an important role in locomotion (Gosgnach et al, 2006;Zhang et al, 2014). Our Prdm12 knockdown experiments indicate that the aINs, the homologues of V1 INs, are required for swimming movement in Xenopus, as observed for CiA INs in zebrafish (Zannino et al, 2014).…”

“…In aquatic vertebrates, this class of INs comprises only one type of multifunctional INs, known as circumferential ipsilateral ascending neurons (CiA) in fish and ascending interneurons (aINs) in frogs. In mammals, the V1 class of INs that plays a crucial role in regulating the rhythm of locomotor outputs and flexor-extensor inhibition (Gosgnach et al, 2006;Zhang et al, 2014) comprises a large variety of derivatives, including Renshaw cells (RCs) and putative reciprocal Ia inhibitory INs (Ia INs) (Alvarez et al, 2005;Siembab et al, 2010;BenitoGonzalez and Alvarez, 2012;Francius et al, 2013). In the chick, the population of En1-expressing neurons in the embryonic spinal cord has equally been shown to be heterogeneous (Wenner et al, 2000).…”

The late and dual origin of cerebrospinal fluid-contacting neurons in the mouse spinal cord

“…The transcription factors Gata2 and Gata3 have been considered to be selective indicators of spinal V2b identity (Karunaratne et al, 2002;Peng et al, 2007;Lundfald et al, 2007;Zhang et al, 2014). However, we provide compelling evidence that CSF-cNs do not belong to the V2b neuronal lineage, although both populations share the expression of Gata2/3 proteins.…”

“…1E,G,H) (Sapir et al, 2004;Zhang et al, 2014Zhang et al, , 2008, whereas V2a interneurons were detected by Chx10 (Vsx2 -Mouse Genome Informatics) staining (Fig. 1F).…”

“…1I, arrowhead) (Zhang et al, 2014;Lundfald et al, 2007), and a second group in the vicinity of the central canal (Fig. 1I, arrow).…”