Elsevier

Neuroscience

Volume 162, Issue 4, 15 September 2009, Pages 1377-1397
Neuroscience

Systems Neuroscience
Research Paper
Locomotor networks are targets of modulation by sensory transient receptor potential vanilloid 1 and transient receptor potential melastatin 8 channels

https://doi.org/10.1016/j.neuroscience.2009.05.063Get rights and content

Abstract

It is well recognized that proprioceptive afferent inputs can control the timing and pattern of locomotion. C and Aδ afferents can also affect locomotion but an unresolved issue is the identity of the subsets of these afferents that encode defined modalities. Over the last decade, the transient receptor potential (TRP) ion channels have emerged as a family of non-selective cation conductances that can label specific subsets of afferents. We focus on a class of TRPs known as ThermoTRPs which are well known to be sensor receptors that transduce changes in heat and cold. ThermoTRPs are known to help encode somatosensation and painful stimuli, and receptors have been found on C and Aδ afferents with central projections onto dorsal horn laminae. Here we show, using in vitro neonatal mouse spinal cord preparations, that activation of both spinal and peripheral transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential melastatin 8 (TRPM8) afferent terminals modulates central pattern generators (CPGs). Capsaicin or menthol and cooling modulated both sacrocaudal afferent (SCA) evoked and monoaminergic drug-induced rhythmic locomotor-like activity in spinal cords from wild type but not TRPV1-null (trpv1−/−) or TRPM8-null (trpm8−/−) mice, respectively. Capsaicin induced an initial increase in excitability of the lumbar motor networks, while menthol or cooling caused a decrease in excitability. Capsaicin and menthol actions on CPGs involved excitatory and inhibitory glutamatergic mechanisms, respectively. These results for the first time show that dedicated pathways of somatosensation and pain identified by TRPV1 or TRPM8 can target spinal locomotor CPGs.

Section snippets

Experimental procedures

Experiments were performed on Swiss Webster mice (Charles River Laboratories, Senneville, Quebec, Canada), transient receptor potential vanilloid 1-null mice (trpv1−/−) (B6.129X1-Trpv1tm1Jul/J, The Jackson Laboratory, Bar Harbor, Maine, USA), transient receptor potential melastatin 8-null mice (trpm8−/−) (generated as described in; Dhaka et al., 2007). Mice used for all experiments in the study were between postnatal days (P) 0 and P3. The animals were anesthetized by hypothermia, decapitated

TRPV1 modulates SCA evoked locomotor rhythm

To address whether modulation of subclasses of C and Aδ afferent inputs alters the excitability of spinal motor circuits, we used a stimulus paradigm which activated SCA (Lev-Tov et al 2000, Whelan et al 2000). These afferents likely synapse onto interneurons which project directly or indirectly into the ventrolateral funiculus (VLF) and in turn onto the lumbar CPG (Fig. 2C) (Strauss and Lev-Tov, 2003). We activated the subclass of TRPV1-positive C and Aδ afferents in the SCA pathway by using

Discussion

The goal of this study was to identify the role of distinct somatosensory and nociceptive afferents in the control of locomotion and to describe a set of tools to effectively do so using isolated spinal cord preparations. To accomplish this, we focused on the modulation of thermoTRPs, which underlie the transduction of hot and cold sensation in the skin (Venkatachalam and Montell, 2007). These receptors are located both in the peripheral and central terminals of afferents (Julius and Basbaum

Acknowledgments

We would like to thank Michelle Tran for her excellent technical assistance. We greatly appreciate ongoing support from the Alberta Heritage Foundation for Medical Research, the Canadian Institutes of Health Research, and the University of Calgary. Dr. Sravan Mandadi was supported by a fellowship from the Alberta Heritage Foundation for Medical Research. Dr. Stan Nakanishi was supported by a fellowship from the Hotchkiss Brain Institute.

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