Long ascending propriospinal neurons provide flexible, context-specific control of interlimb coordination
Abstract
Within the cervical and lumbar spinal enlargements, central pattern generating (CPG) circuitry produces the rhythmic output necessary for limb coordination during locomotion. Long propriospinal neurons that inter-connect these CPGs are thought to secure hindlimb-forelimb coordination, ensuring that diagonal limb pairs move synchronously while the ipsilateral limb pairs move out-of-phase during stepping. Here, we show that silencing long ascending propriospinal neurons (LAPNs) that interconnect the lumbar and cervical CPGs disrupts left-right limb coupling of each limb pair in the adult rat during overground locomotion on a high-friction surface. These perturbations occurred independent of the locomotor rhythm, intralimb coordination, and speed-dependent (or any other) principal features of locomotion. Strikingly, the functional consequences of silencing LAPNs are highly context-dependent; the phenotype was not expressed during swimming, treadmill stepping, exploratory locomotion, or walking on an uncoated, slick surface. These data reveal surprising flexibility and context-dependence in the control of interlimb coordination during locomotion.
Data availability
Source data has been provided for: Figures 2, 3, 4 and 5, Figure 1 figure supplement 1 and Figure 4 figure supplement 2
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (R01 NS089324)
- Scott R Whittemore
- David SK Magnuson
National Institute of Neurological Disorders and Stroke (P30 GM103507)
- Scott R Whittemore
- David SK Magnuson
Kentucky Spinal Cord and Head Injury Research Trust (13-14)
- Scott R Whittemore
- David SK Magnuson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to the approved institutional animal care and use committee (IACUC) protocol (#16669) of the University of Louisville. All surgery was performed under sodium pentobarbital or isoflurane anesthesia, and every effort was made to minimize suffering.
Copyright
© 2020, Pocratsky et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,009
- views
-
- 310
- downloads
-
- 33
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
The experience-dependent spatial cognitive process requires sequential organization of hippocampal neural activities by theta rhythm, which develops to represent highly compressed information for rapid learning. However, how the theta sequences were developed in a finer timescale within theta cycles remains unclear. In this study, we found in rats that sweep-ahead structure of theta sequences developing with exploration was predominantly dependent on a relatively large proportion of FG-cells, that is a subset of place cells dominantly phase-locked to fast gamma rhythms. These ensembles integrated compressed spatial information by cells consistently firing at precessing slow gamma phases within the theta cycle. Accordingly, the sweep-ahead structure of FG-cell sequences was positively correlated with the intensity of slow gamma phase precession, in particular during early development of theta sequences. These findings highlight the dynamic network modulation by fast and slow gamma in the development of theta sequences which may further facilitate memory encoding and retrieval.
-
- Neuroscience
The perception of innocuous temperatures is crucial for thermoregulation. The TRP ion channels TRPV1 and TRPM2 have been implicated in warmth detection, yet their precise roles remain unclear. A key challenge is the low prevalence of warmth-sensitive sensory neurons, comprising fewer than 10% of rodent dorsal root ganglion (DRG) neurons. Using calcium imaging of >20,000 cultured mouse DRG neurons, we uncovered distinct contributions of TRPV1 and TRPM2 to warmth sensitivity. TRPV1’s absence – and to a lesser extent absence of TRPM2 – reduces the number of neurons responding to warmth. Additionally, TRPV1 mediates the rapid, dynamic response to a warmth challenge. Behavioural tracking in a whole-body thermal preference assay revealed that these cellular differences shape nuanced thermal behaviours. Drift diffusion modelling of decision-making in mice exposed to varying temperatures showed that TRPV1 deletion impairs evidence accumulation, reducing the precision of thermal choice, while TRPM2 deletion increases overall preference for warmer environments that wildtype mice avoid. It remains unclear whether TRPM2 in DRG sensory neurons or elsewhere mediates thermal preference. Our findings suggest that different aspects of thermal information, such as stimulation speed and temperature magnitude, are encoded by distinct TRP channel mechanisms.