Reversible silencing of lumbar spinal interneurons unmasks a task-specific network for securing hindlimb alternation

Abstract

Neural circuitry in the lumbar spinal cord governs two principal features of locomotion, rhythm and pattern, which reflect intra- and interlimb movement. These features are functionally organized into a hierarchy that precisely controls stepping in a stereotypic, speed-dependent fashion. Here, we show that a specific component of the locomotor pattern can be independently manipulated. Silencing spinal L2 interneurons that project to L5 selectively disrupts hindlimb alternation allowing a continuum of walking to hopping to emerge from the otherwise intact network. This perturbation, which is independent of speed and occurs spontaneously with each step, does not disrupt multi-joint movements or forelimb alternation, nor does it translate to a non-weight-bearing locomotor activity. Both the underlying rhythm and the usual relationship between speed and spatiotemporal characteristics of stepping persist. These data illustrate that hindlimb alternation can be manipulated independently from other core features of stepping, revealing a striking freedom in an otherwise precisely controlled system.

Long ascending propriospinal neurons provide flexible, context-specific control of interlimb coordination

“…interneurons that project to L5 were silenced 18 . In that case, hindlimb alternation was selectively disrupted, allowing a spectrum of coupling patterns to be expressed, while other essential features of locomotion were once again preserved 18 .…”

“…interneurons that project to L5 were silenced 18 . In that case, hindlimb alternation was selectively disrupted, allowing a spectrum of coupling patterns to be expressed, while other essential features of locomotion were once again preserved 18 . Together, these studies indicate that intersegmental projecting lumbar pathways are key distributors of temporal information that can be used for maintaining left-right alternation during overground locomotion, and that hindlimbforelimb coordination is either secured by other means or is less vulnerable to disruption potentially requiring silencing of larger numbers or a wider range of long-propriospinal neurons.…”

“…Given the critical involvement of cervical and lumbar CPGs for locomotion and the anatomical profile of the long ascending projections which connect these rhythmogenic foci, we set out to silence LAPNs in the freely behaving adult rat. We used the dual-virus TetOn system originally developed by Isa and colleagues (18), which allows doxycycline-induced reversible silencing of anatomically Collectively, these data suggest that the cervical projections derived from double-infected LAPNs express eTeNT and were silenced in vivo.…”

Synapse preservation and decreased glial reactions following ventral root crush (VRC) and treatment with 4‐hydroxy‐tempo (TEMPOL)

“…Another possible explanation is that the antioxidant role of TEMPOL undermined glutamate excitotoxicity. In this case, afferents that are fundamentally important for motor coordination would be preserved, particularly those in deeper laminae (IV–VI and X) (Oliveira et al, ; Pocratsky et al, ).…”

Spinal Control of Locomotion: Individual Neurons, Their Circuits and Functions

“…Long PINs were also shown to synchronize forelimb and hindlimb activity during stepping ( Miller et al, 1973 ; Jankowska et al, 1974 ). Inhibition of long ascending PINs can disrupt interlimb coordination ( Pocratsky et al, 2017 ), and blocking transmission in the thoracic cord uncouples the rhythmic activity from the cervical and lumbar enlargements ( Ballion et al, 2001 ; Juvin et al, 2005 ).…”