The sensory neurons of touch

Abstract

The somatosensory system decodes a wide range of tactile stimuli and thus endows us with a remarkable capacity for object recognition, texture discrimination, sensory-motor feedback and social exchange. The first step leading to perception of innocuous touch is activation of cutaneous sensory neurons called low-threshold mechanoreceptors (LTMRs). Here, we review the properties and functions of LTMRs, emphasizing the unique tuning properties of LTMR subtypes and the organizational logic of their peripheral and central axonal projections. We discuss the spinal cord neurophysiological representation of complex mechanical forces acting upon the skin and current views of how tactile information is processed and conveyed from the spinal cord to the brain. An integrative model in which ensembles of impulses arising from physiologically distinct LTMRs are integrated and processed in somatotopically aligned mechanosensory columns of the spinal cord dorsal horn underlies the nervous system's enormous capacity for perceiving the richness of the tactile world.

Figure 1. The organization of cutaneous mechanoreceptors in skin

Innocuous touch information is processed by both glabrous (hairless, A) and hairy skin (B). A) In glabrous skin, innocuous touch is mediated by four types of mechanoreceptors. The Merkel cell-neurite complex is in the basal layer of the epidermis and it consists of clusters of Merkel cells making synapse-like associations with enlarged nerve terminals branching from a single Aβ fiber. This complex and its associated SAI-LTMR responses help us in reconstructing acute spatial images of tactile stimuli. Meissner corpuscles are localized in the dermal papillae and consist of horizontal lamellar cells embedded in connective tissue. Their characteristic RAI-LTMR responses detect movement across the skin. Ruffini endings are localized deep in the dermis and are morphologically similar to the Golgi tendon organ, a large and thin spindle-shaped cylinder composed of layers of perineural tissue. Historically, Ruffini endings have been associated with SAII-LTMR responses, which respond best to skin stretch, though such correlations remain highly controversial. Lastly, Pacinian corpuscles are located in the dermis of glabrous skin where its characteristic onion-shaped lamellar cells encapsulate a single Aβ ending. Their well-recognized RAII-LTMR responses detect high frequency vibration. B) In hairy skin, tactile stimuli are transduced through three types of hair follicles, defined in the mouse as guard, awl/auchenne, and zigzag. The longest hair type, guard hairs, are associated with touch domes at the apex and Aβ-LTMR longitudinal lanceolate endings at the base. Awl/auchene hairs are triply innervated by C-LTMRs, Aδ-LTMRs, and Aβ-LTMRs longitudinal lanceolate endings. Zigzag hair follicles are the shortest and are innervated by both C- and Aδ-LTMRs longitudinal lanceolate endings. In addition, all three hair follicle types are innervated by circumferential lanceolate endings whose physiological properties remain unknown. Noxious touch is detected by free nerve endings found in the epidermis of both glabrous and hairy skin and are characterized by both Aδ- and C-HTMR responses. Abbreviations: SA, slowly adapting; RA, rapidly adapting; LTMR, low-threshold mechanoreceptor; HTMR, high-threshold mechanoreceptor; SC, stratum corneum; SG, stratum granulosum; SS, stratum spinosum; SB, stratum basalis.

Figure 2. Postulated LTMR activity codes

Heatmap guide to the relative sensitivities and tuning properties of hairy skin LTMRs in response to common tactile stimuli. A) Indentation on skin, like a poke, would most optimally activate SAI-LTMRs associated with guard hair touch domes. Though dominant for this particular stimulus, SAI-LTMRs would not be the only LTMR represented in the ensemble of impulses traveling to the CNS. B) A firm stroke, like rubbing a cat’s back, would result in a distinct ensemble of the activities of SA- and RA-LTMRs as well as the ultrasensitive Aδ- and C-LTMRs, which respond well to hair follicle deflection. C) A gentle breeze is likely to activate all LTMRs forming longitudinal lanceolate endings, the Aβ RA-, Aδ- and C-LTMRs, whereas SAI-LTMRs endings, would be relatively silent in this ensemble response. A slow caress of the skin, as with a mother’s nurturing touch, is likely to activate hair follicle associated LTMR subtypes and especially C-LTMRs, which are particularly well tuned to gentle stroking of the skin thus providing a unique “LTMR caress ensemble”. Circumferential endings are depicted in white in this model as it is still unknown if or how they respond to skin stimulation. Abbreviations: SA, slowly adapting; RA, rapidly adapting; LTMR, low-threshold mechanoreceptor.

Figure 3. The anatomy of LTMR processing units of the spinal cord dorsal horn

LTMR subtypes develop unique branching and collateral morphologies critical for processing of innocuous touch information by the spinal cord. A-B) C-and Aδ-LTMRs do not bifurcate upon exiting the dorsal root, instead they turn rostrally before diving into their respective lamina (; unpublished results). Inset in panel A shows the laminar organization of the spinal cord which is divided into ten laminae (I-X) based on variations in cell density. The dorsal horn is boxed in red. C-LTMRs arborize directly into lamina IIiv, while Aδ-LTMRs send C-shaped collaterals that arborize into flame-shaped endings overlapping with C-LTMRs in lamina IIiv but also extending into lamina III. C-D) RA- and SA-LTMRs bifurcate upon exiting the dorsal root, with a rostral branch extending through the dorsal columns to synapse onto dorsal column nuclei in the medulla and a caudal branch that ends in a collateral several segments away. Along the way both LTMR types sprout several collaterals that, like Aδ-LTMRs, take a C-shape trajectory before arborizing in lamina III-V. E) Mouse hairy skin is organized in clusters containing one centrally located guard hair, about 20 surrounding awl/auchene hair and about 80 interspersed zigzag hairs. Each mouse hair follicle within these clusters receives a unique and invariant combination of physiologically and morphologically distinct sensory neurons subtypes. Therefore, from a particular patch of skin, clusters of hair follicles and associated LTMR subtypes propagate sensory information that converges onto columnar LTMR-processing units in the dorsal horn. Adapted from Brown, 1981a.

Figure 4. The neural components of the spinal cord dorsal horn

A) Central terminations and columnar organization of Aβ RA, Aβ SA, Aδ- and C-LTMRs. These LTMR processing units represent inputs onto various locally projecting interneurons (B) and long range projection neurons (C) whose cell bodies and dendrites reside in the dorsal horn. B) The vast majority of neurons in lamina I-III have axons that remain in the spinal cord and are therefore defined as locally projecting interneurons. Within lamina I three major morphological cell types have been characterized: pyramidal, fusiform, and multipolar, though some of these morphological forms can be associated with projection neurons also found in lamina I. The most thoroughly characterized dorsal horn lamina is the substantia gelatinosa, lamina II, studied extensively in several rodent species by Perl and colleagues (Grudt and Perl, 2002). Within this lamina there are four main morphological classes of interneurons: Islet, central, vertical and radial cells. More morphological types exist in deeper lamina, though they remain to be physiologically classified, one example is the pyramidal interneuron described in cat (Mannen and Sugiura, 1976). Local interneurons in the dorsal horn may also be classified neurochemically, either by neurotransmitter, neuropeptide, and/or calcium-binding protein expression, for example, PKCγ+ interneurons are exclusively found between lamina II/III (Malmberg et al., 1997). C) There are three major types of projection neurons in dorsal horn that carry tactile information out of the spinal cord into brain centers. Pain and temperature information is carried by projection neurons that make up the anterolateral tract system. Their cell bodies reside in lamina I and III-V and their projections decussate in the ventral commissure and ascend through the anterolateral white matter of the spinal cord. Projection neurons concerned with innocuous tactile information include the post-synaptic dorsal column (PSDCs) and the spinocervical tract neurons (SCT). Their cell bodies reside in lamina III-V. PSDC neuronal projections ascend through the dorsal columns, while SCT projections ascend though the dorsolateral white matter of the spinal cord. Abbreviations: LCN, lateral cervical nucleus; DCN, dorsal column nuclei.

Figure 5. Touch circuits in the CNS

Morphological differences between the direct dorsal column (DC) pathway and the indirect post-synaptic dorsal column (PSDC) and spinocervical tract (SCT) pathways provide evidence that these main ascending systems sub-serve different roles in propagating tactile information from the periphery to the brain. A) PSDC neurons receive information from both glabrous and hairy skin LTMRs. Their projections ascend through the dorsal columns (DC) to synapse onto targets in the dorsal column nuclei (DCN). PSDC neurons from the lower thoracic and lumbar/sacral spinal cord synpse onto neurons in the cueneate nucleus (CN), while those from cervical and upper thoracic regions synapse onto neurons of the gracile nucleus (GN). From the DCN, second order neurons decussate and ascend through the medial lemniscus pathway to synapse onto the ventral posterior nuclear (VPN) complex of the thalamus. B) SCT neurons receive information almost exclusively from hairy skin. Their projections ascend through the dorsolateral white matter for synapse onto the lateral cervical nucleus (LCN) located at cervical level 1–3. From there, LCN second order neurons decussate through the dorsal commisure and join the DC/PSDC pathway in the medial lemniscus. From the VPN, third order neurons carrying innocuous information from both the direct and indirect pathways synapse onto the somatosensory cortex. New molecular-genetic tools for understanding the cellular and synaptic organization and functional requirements of the direct DC pathway and the indirect PSDC and SCT pathways will dissect relative contributions of these ascending pathways to the perception of touch.