Identification of a Spinal Circuit for Light Touch and Fine Motor Control

Abstract

Sensory circuits in the dorsal spinal cord integrate and transmit multiple cutaneous sensory modalities including the sense of light touch. Here we identify a population of excitatory interneurons (INs) in the dorsal horn that are important for transmitting innocuous light touch sensation. These neurons express the ROR alpha (RORα) nuclear orphan receptor and are selectively innervated by cutaneous low threshold mechanoreceptors (LTMs). Targeted removal of RORα INs in the dorsal spinal cord leads a marked reduction in behavioral responsiveness to light touch without affecting responses to noxious and itch stimuli. RORα IN-deficient mice also display a selective deficit in corrective foot movements. This phenotype, together with our demonstration that the RORα INs are innervated by corticospinal and vestibulospinal projection neurons, argues that the RORα INs direct corrective reflex movements by integrating touch information with descending motor commands from the cortex and cerebellum.

Making sense out of spinal cord somatosensory development

“…The RORα neurons are also indirectly activated by Cfibers. Since these neurons are mostly LMX1B + and PAX2 − , they are probably a subset of dI5/dIL B VGLUT2 + neurons (Bourane et al, 2015b;Del Barrio et al, 2013). Consistent with the function of their sensory inputs, the ablation of RORα + neurons in the mouse spinal cord causes deficiencies in dynamic and static light touch, but not pain, thermosensation or itch.…”

“…A second population of neurons defined by RORα expression is reported to be involved in detecting cutaneous inputs necessary for light touch and corrective foot movements (Bourane et al, 2015b). These RORα + cells are located in lamina II iv /III and are innervated by primary sensory neurons that terminate in Meissner corpuscles, Ruffini corpuscles and Merkel cells as well as D-hair afferents and Aβ and Aδ afferents that terminate as transverse lanceolate endings in hairy skin.…”

“…Genetic manipulation of dI5/ dIL B neurons as a whole (via elimination of spinal cord TLX3) leads to defects in dynamic light touch, noxious thermosensation, mechanical and chemical pain, and itch, but not in motor control (Xu et al, 2013). Further dissection of dI5/dIL B lineages has shown that the RORα + subset is in part responsible for dynamic light touch, as discussed above (Bourane et al, 2015b), while noxious thermosensation appears to derive from a LMX1B + population -potentially the neurons in lamina I that contribute to the spinothalamic tract (STT) division of the ALS (Szabo et al, 2015;Todd, 2010). Meanwhile, at least three subpopulations (positive for somatostatin, SOM, in laminae II-III, calretinin in the inner part of lamina II and the transient vesicular glutamate transporter 3, VGLUT3, in laminae II-III) are important for mechanical allodynia, a condition in which touch becomes painful after injury (Duan et al, 2014;Peirs et al, 2015).…”

“…These behavioral defects are similar to those seen in caudal Atoh1 conditional knockouts (Yuengert et al, 2015), indicating that both dI1 and dI3 neurons may feed into similar proprioceptive and cutaneous networks that execute proper gross motor control. By contrast, Merkel cells (light touch sensory inputs) and RORα interneurons, which relay light touch inputs, are not required for gross motor behavior (Bourane et al, 2015b;Maricich et al, 2012), but RORα interneurons have been shown to play a role in fine motor control. Therefore, it will be interesting to see how dI1 and dI3 neurons may receive different sensory inputs compared with RORα neurons and how they might differentially send this information to motor neurons, potentially providing insights into circuits that direct gross versus fine motor control.…”

“…TRPM8 (Bautista et al, 2007), TRPV1 (Villeda et al, 2006), MRGPRD (Zylka et al, 2005), SP, CGRP, IB4, TRKA (Snider and McMahon, 1998), VGLUT3 (Seal et al, 2009), TRKB, NPY2R (Li et al, 2011), TRKC, PV (Arber et al, 2000), VGLUT1, Vglut1 (Alvarez et al, 2004;Hantman and Jessell, 2010;Llewellyn-Smith et al, 2007), NK1R, PKCγ (Todd, 2010), Grpr (Sun and Chen, 2007), Som, Dyn (Duan et al, 2014;Xu et al, 2008), LMX1B, RORα, MAFA, LBX1, TLX3, PAX2, GBX1 (Bourane et al, 2015b;Del Barrio et al, 2013;Szabo et al, 2015), Npy (Bourane et al, 2015a). of the direct downstream targets of these TFs that could connect them to terminal differentiation processes such as axon guidance and neurotransmitter or neuropeptide fate (Avraham et al, 2009;Brohl et al, 2008;Cheng et al, 2004Cheng et al, , 2005Hobert, 2011;Pillai et al, 2007).…”