V3 Spinal Neurons Establish a Robust and Balanced Locomotor Rhythm during Walking

Abstract

Summary A robust and well-organized rhythm is a key feature of many neuronal networks, including those that regulate essential behaviors such as circadian rhythmogenesis, breathing and locomotion. Here we show that excitatory V3-derived neurons are necessary for a robust and organized locomotor rhythm during walking. When V3-mediated neurotransmission is selectively blocked by the expression of the Tetanus toxin light chain subunit (TeNT), the regularity and robustness of the locomotor rhythm is severely perturbed. A similar degeneration in the locomotor rhythm occurs when the excitability of V3-derived neurons is reduced acutely by ligand-induced activation of the allatostatin receptor. The V3-derived neurons additionally function to balance the locomotor output between both halves of the spinal cord, thereby ensuring a symmetrical pattern of locomotor activity during walking. We propose that the V3 neurons establish a robust and balanced motor rhythm by distributing excitatory drive between both halves of the spinal cord.

Netrin-1-Dependent Spinal Interneuron Subtypes Are Required for the Formation of Left-Right Alternating Locomotor Circuitry

“…Despite the severe overall loss of CINs, the remaining neurons appear sufficient to maintain a coordinated activity over the midline, albeit with a strict left-right synchronous pattern. This suggests that the V3 population is an important component of the left-right synchrony circuitry, which is in line with previous findings where V3 neurons were suggested to balance the motor outputs produced in each half of the spinal cord (Zhang et al, 2008). Neurons originating from the V0 population, which was only partially affected, could in principle also be involved in left-right synchrony.…”

“…Mice in which the V3 derived neurons were genetically manipulated to disrupt their synaptic transmission maintained the ability of leftright alternation (Zhang et al, 2008). In contrast, in Netrin-1 mutant mice, the only CIN population left intact in its entirety was the V3 interneurons.…”

“…Dorsal progenitor cells give rise to six early classes of neurons, dI1 to dI6, and ventral progenitors give rise to motor neurons and four classes of interneurons, V0 to V3. Several of the ventraloriginating populations have recently been shown to be involved in specific aspects of locomotion (Gosgnach et al, 2006;Crone et al, 2008;Zhang et al, 2008). With regard to left-right coordination, the rhythms of fictive locomotion were irregular with episodes of synchrony and alternation (Lanuza et al, 2004) or drifting in and out of strict alternation (Crone et al, 2008), perhaps best described as uncoordinated phenotypes.…”

Optogenetic dissection reveals multiple rhythmogenic modules underlying locomotion

“…Moreover, light-induced locomotor-like activity has a higher burst frequency than seen with other methods (up to 2.7 Hz), is well tuned, and is instantaneously turned on with the appropriate pattern. Drug-induced locomotor-like activity is readily evoked and can be maintained for hours, permitting long timespan analysis in wild type as well as mutant and lesioned animals (45)(46)(47)(48)(49)(50). Although the activity most likely uses the same networks as under in vivo conditions, an obvious drawback is that the drugs act upon every neuron in the spinal cord, not all of which are necessarily components of the locomotor network.…”

Organization of Functional Synaptic Connections between Medullary Reticulospinal Neurons and Lumbar Descending Commissural Interneurons in the Neonatal Mouse

“…In the mouse spinal cord, two broad populations of excitatory INs have been identified by their intraspinal axonal trajectories and developmental expression of molecular markers: (1) ipsilaterally projecting INs that express the transcription factors HB9 (Hinckley et al, 2005;Wilson et al, 2005), Chx10 (AlMosawie et al, 2007;Lundfald et al, 2007), or Sim1 (Zhang et al, 2008; J. C. Glover, unpublished observations); and (2) contralaterally projecting INs (CINs) that express the transcription factors Evx1 Pierani et al, 2001;Lanuza et al, 2004) or Sim1 (Zhang et al, 2008;Hägglund et al, 2010). It is clearly established in the adult cat that excitatory CINs receive inputs from pontine reticulospinal neurons (Jankowska et al, 2009 and references therein).…”