The Functional Organization of Cutaneous Low-Threshold Mechanosensory Neurons

The Solomon H Snyder Department of Neuroscience and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell (Impact Factor: 32.24). 12/2011; 147(7):1615-27. DOI: 10.1016/j.cell.2011.11.027
Source: PubMed


Innocuous touch of the skin is detected by distinct populations of neurons, the low-threshold mechanoreceptors (LTMRs), which are classified as Aβ-, Aδ-, and C-LTMRs. Here, we report genetic labeling of LTMR subtypes and visualization of their relative patterns of axonal endings in hairy skin and the spinal cord. We found that each of the three major hair follicle types of trunk hairy skin (guard, awl/auchene, and zigzag hairs) is innervated by a unique and invariant combination of LTMRs; thus, each hair follicle type is a functionally distinct mechanosensory end organ. Moreover, the central projections of Aβ-, Aδ-, and C-LTMRs that innervate the same or adjacent hair follicles form narrow LTMR columns in the dorsal horn. These findings support a model of mechanosensation in which the activities of Aβ-, Aδ-, and C-LTMRs are integrated within dorsal horn LTMR columns and processed into outputs that underlie the perception of myriad touch sensations.

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    • "Enhanced efficacy of spinally administered 2 adrenoceptor agonists (Stanfa and Dickenson, 1994; Mansikka and Pertovaara, 1995; Tsuruoka et al., 2003), increased noradrenergic innervation to DH (Ma and Eisenach, 2003) and upregulation of spinal 2 adrenoceptors and increased spinal cord NA content (Satoh and Omote, 1996) all indicate profound alrerations to descending adrenergic inputs to the DH in neuropathic pain. A recent paper addressed the clinically relevant question of why only a minority of patients develop chronic neuropathic pain following the same nerve lesion (De Felice et al., 2011). The suggestion from the authors that a descending noradrenergic mechanism could actually protect from pain put brain to spinal cord pathways once again at the forefront of pain modulation, and of great interest was the proposal that nerve injuryinduced pain could ultimately depend on descending drives. "
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    ABSTRACT: Maladaptive plasticity within the dorsal horn of the spinal cord is a key substrate for development of neuropathic pain following peripheral nerve injury. Advances in genetic engineering, tracing techniques and opto-genetics are leading to a much better understanding of the complex circuitry of the spinal dorsal horn and the radical changes evoked in such circuitry by nerve injury. These changes can be viewed at multiple levels including: synaptic remodelling including enhanced excitatory and reduced inhibitory drive, morphological and electrophysiological changes which are observed both to primary afferent inputs as well as dorsal horn neurons, and ultimately circuit-level rewiring which leads to altered connectivity and aberrant processing of sensory inputs in the dorsal horn. The dorsal horn should not be seen in isolation but is subject to important descending modulation from the brainstem, which is further dysregulated by nerve injury. Understanding which changes relate to specific disease-states is essential, and recent work has aimed to stratify patient populations in a mechanistic fashion. In this review we will discuss how such pathophysiological mechanisms may lead to the distressing sensory phenomena experienced by patients suffering neuropathic pain, and the relationship of such mechanisms to current and potential future treatment modalities. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 05/2015; 300. DOI:10.1016/j.neuroscience.2015.05.020 · 3.36 Impact Factor
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    • "In mice, different hair follicle types are innervated by distinct receptor complements; therefore, individual hairs serve as units of multi-modal tactile integration (Li et al., 2011). Similarly, we found that some hair follicles were associated with both lanceolate endings and Merkel cells. "
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    ABSTRACT: Flight maneuvers require rapid sensory integration to generate adaptive motor output. Bats achieve remarkable agility with modified forelimbs that serve as airfoils while retaining capacity for object manipulation. Wing sensory inputs provide behaviorally relevant information to guide flight; however, components of wing sensory-motor circuits have not been analyzed. Here, we elucidate the organization of wing innervation in an insectivore, the big brown bat, Eptesicus fuscus. We demonstrate that wing sensory innervation differs from other vertebrate forelimbs, revealing a peripheral basis for the atypical topographic organization reported for bat somatosensory nuclei. Furthermore, the wing is innervated by an unusual complement of sensory neurons poised to report airflow and touch. Finally, we report that cortical neurons encode tactile and airflow inputs with sparse activity patterns. Together, our findings identify neural substrates of somatosensation in the bat wing and imply that evolutionary pressures giving rise to mammalian flight led to unusual sensorimotor projections. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 04/2015; 11(6). DOI:10.1016/j.celrep.2015.04.001 · 8.36 Impact Factor
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    • "central axonal projections that terminate within lamina IIiv/III of the spinal cord dorsal horn. The peripheral projections of Ad- LTMRs form longitudinal lanceolate endings associated with both awl/auchene and zigzag hairs of trunk hairy skin (Li et al., 2011). To facilitate examination of the physiological and morphological properties of individually labeled Ad-LTMRs, we generated a TrkB CreER knockin mouse line in which a fusion cassette consisting of Cre recombinase and a triple mutant form of the human estrogen receptor (CreERT2) was introduced via homologous recombination into the first coding exon of the TrkB gene (Figure S1 "
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    ABSTRACT: The perception of touch, including the direction of stimulus movement across the skin, begins with activation of low-threshold mechanosensory neurons (LTMRs) that innervate the skin. Here, we show that murine Aδ-LTMRs are preferentially tuned to deflection of body hairs in the caudal-to-rostral direction. This tuning property is explained by the finding that Aδ-LTMR lanceolate endings around hair follicles are polarized; they are concentrated on the caudal (downward) side of each hair follicle. The neurotrophic factor BDNF is synthesized in epithelial cells on the caudal, but not rostral, side of hair follicles, in close proximity to Aδ-LTMR lanceolate endings, which express TrkB. Moreover, ablation of BDNF in hair follicle epithelial cells disrupts polarization of Aδ-LTMR lanceolate endings and results in randomization of Aδ-LTMR responses to hair deflection. Thus, BDNF-TrkB signaling directs polarization of Aδ-LTMR lanceolate endings, which underlies direction-selective responsiveness of Aδ-LTMRs to hair deflection. PAPERCLIP: Copyright © 2014 Elsevier Inc. All rights reserved.
    Cell 12/2014; 159(7):1640-1651. DOI:10.1016/j.cell.2014.11.038 · 32.24 Impact Factor
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