The role of V3 neurons in speed-dependent interlimb coordination during locomotion in mice

Abstract

Speed-dependent interlimb coordination allows animals to maintain stable locomotion under different circumstances. We have previously demonstrated that a subset of spinal V3 neurons contributes to stable locomotion by mediating mutual excitation between left and right lumbar rhythm generators (RGs). Here, we expanded our investigation to the V3 neurons involved in ascending long propriospinal interactions (aLPNs). Using retrograde tracing, we revealed a subpopulation of lumbar V3 aLPNs with contralateral cervical projections. V3OFF mice, in which all V3 neurons were silenced, had a significantly reduced maximal locomotor speed, were unable to move using stable trot, gallop, or bound, and predominantly used lateral-sequence walk. To understand the functional roles of V3 aLPNs, we adapted our previous model of spinal circuitry controlling quadrupedal locomotion (Danner et al., 2017), by incorporating diagonal V3 aLPNs mediating inputs from each lumbar RG to the contralateral cervical RG. The updated model reproduces our experimental results and suggests that locally projecting V3 neurons, mediating left–right interactions within lumbar and cervical cords, promote left–right synchronization necessary for gallop and bound, whereas the V3 aLPNs promote synchronization between diagonal fore and hind RGs necessary for trot. The model proposes the organization of spinal circuits available for future experimental testing.

Multimodal sensory control of motor performance by glycinergic interneurons of the spinal cord deep dorsal horn

“…Therefore, accommodating their altered gait transitions, dPV abl mice showed altered intalimb and interlimb forelimb-hindlimb but not left-right coordination. This is surprising, given we did not find evidence for propriospinal dPV neurons, those thought to be responsible for modulating hindlimb-forelimb ipsilateral coordination (H. Zhang et al 2022; Danner et al 2016; Kiehn 2016). This result could be a consequence of the specific ablation of dPVs in the lumbosacral region in our study.…”

“…Andersson and Grillner 1981; 1983; Akay et al 2014; Guertin et al 1995; J and Kg 1980; Stecina, Quevedo, and McCrea 2005; L. J. G. Bouyer and Rossignol 2003a; 2003b; Duysens 1977; Schomburg et al 1998b; Grillner and Rossignol 1978; Hiebert et al 1996). Third, dPVs may alter the recruitment of premotor neurons with a speed-dependent role in locomotion, such as the V0 D, V0 v, V1, V2a, V2b and V3 interneurons (Crone et al 2008; Gosgnach et al 2006; Callahan et al 2019; H. Zhang et al 2022; Talpalar et al 2013). Our anatomical, electrophysiological, and EMG data supports contributions from each explanation.…”

“…Gait expression was shown to depend on different modules of neuronal ensembles (Kiehn 2016). For example, experimental and computational studies suggest that loss of interneurons that mediate low, intermediate and high speed locomotion lead to loss of walk, trot and gallop/ bound, respectively (Talpalar et al 2013; Bellardita and Kiehn 2015; H. Zhang et al 2022; Danner et al 2016). Our data show that mice with ablated dPVs locomote at higher speeds and prefer to maintain a walk gait over trot.…”

“…J. G. Bouyer and Rossignol 2003a; 2003b; Duysens 1977; Schomburg et al 1998b; Grillner and Rossignol 1978; Hiebert et al 1996). Third, dPVs may alter the recruitment of premotor neurons with a speed-dependent role in locomotion, such as the V0 D, V0 v, V1, V2a, V2b and V3 interneurons (Crone et al 2008; Gosgnach et al 2006; Callahan et al 2019; H. Zhang et al 2022; Talpalar et al 2013).…”

A spinal synergy of excitatory and inhibitory neurons coordinates ipsilateral body movements

“…The ipsilaterally projecting inhibitory V1 and V2b neurons cooperate to regulate flexion and extension alternation and the timing of stance and swing phasing (Bourane et al, 2015;Zhang et al, 2014), thus functioning as integral parts of the half-center modules. The commissural V0 neurons, the ipsilateral V2a neurons and the dual-projecting V3 neurons coordinate limbcoupling and the transition to faster gaits (Bellardita and Kiehn, 2015;Crone et al, 2008Crone et al, , 2009Lanuza et al, 2004;Talpalar et al, 2013;Zhang et al, 2021). For example, when the activity of V0, V2 or V3 neurons is disrupted, mice adopt markedly altered or unstable gaits as locomotor speed increases (Bellardita and Kiehn, 2015;Crone et al, 2008Crone et al, , 2009Lanuza et al, 2004;Talpalar et al, 2013;Zhang et al, 2021).…”