Touch is integral to essential behaviors such as feeding, social bonding and avoiding bodily harm. In mammals, touch is encoded by sensory receptors embedded in the skin. Mammalian skin structure and mechanical properties are dynamic, changing in response to numerous physiological and external conditions, including nutrition, body weight, aging and exposure to environmental factors, such as UV irradiation. Little is known about how these physiologic changes alter neuronal signaling from touch receptors. The objective of this application is to elucidate peripheral mechanisms that govern the firing properties of tactile afferents during normal physiological target-organ changes. The project focuses on mouse slowly adapting type I (SAI) afferents as a model system with unparalleled accessibility for computational and experimental studies. Merkel cells in contact with myelinated cutaneous afferents form gentle-touch receptors that mediate SAI responses. This project is highly relevant to human health because 1) SAI responses in the skin underlie high tactile acuity in humans but little is known about how physiological skin remodeling alters their signaling;and 2) understanding mechanisms of normal neuronal remodeling could identify targets for treating pathological or age-related changes in touch sensitivity. Anatomical studies have shown that skin innervation density changes during normal hair growth in mice. This application will address key open questions: 1) what are the mechanisms that govern innervation changes during hair-follicle cycling, and 2) do changes in innervation lead to altered sensory signaling? The central hypothesis is that structural plasticity of tactile afferents govern touch-evoked firing properties during normal skin remodeling. The hypothesis will be tested with an innovative multidisciplinary approach combining experimental techniques, including neurophysiology, 3D microscopy, quantitative morphometry, tissue biomechanics and novel mouse models, with computational tools such as novel network models of neuronal dynamics, differential equations and solid mechanics.
Aims are to 1) define temporal dynamics and cellular mechanisms of neuronal remodeling during skin renewal, 2) analyze the functional consequences of neuronal remodeling on mechanical encoding, and 3) identify the target cell type and candidate molecular cues that drive neuronal remodeling. This project is conceptually innovative because it tackles a novel question in basic neurobiology that is central to the encoding of touch stimuli. Technically innovation lies in its unique, interdisciplinary approaches to combine experimental biology with computational studies to answer these fundamental questions. By identifying mechanisms that govern the reliability of touch-evoked signals in healthy skin, these studies will set the stage to determine how these mechanisms fail in aging and pathophysiological states.

Public Health Relevance

Touch is essential for navigating our world, yet little is known about how neurons embedded in the skin send reliable information in the face of continuous skin remodeling. Merkel cell-neurite complexes are gentle- touch receptors that convey tactile information regarding object texture, shape and curvature, and these studies will determine how this essential touch receptor adapts to its changing target organ to maintain reliable sensory signaling. This project will resolve fundamental questions in neurobiology and somatosensory coding, which are essential to understand the sense of touch in both healthy skin and pathophysiological states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS073119-05
Application #
8741998
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Gnadt, James W
Project Start
2010-09-15
Project End
2017-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
5
Fiscal Year
2014
Total Cost
$379,273
Indirect Cost
$85,175
Name
Columbia University (N.Y.)
Department
Dermatology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Marshall, Kara L; Clary, Rachel C; Baba, Yoshichika et al. (2016) Touch Receptors Undergo Rapid Remodeling in Healthy Skin. Cell Rep 17:1719-1727
Wang, Yuxiang; Baba, Yoshichika; Lumpkin, Ellen A et al. (2016) Computational modeling indicates that surface pressure can be reliably conveyed to tactile receptors even amidst changes in skin mechanics. J Neurophysiol 116:218-28
Hauser, Steven C; Gerling, Gregory J (2016) Measuring tactile cues at the fingerpad for object compliances harder and softer than the skin. IEEE Haptics Symp 2016:247-252
Marshall, Kara L; Chadha, Mohit; deSouza, Laura A et al. (2015) Somatosensory substrates of flight control in bats. Cell Rep 11:851-8
Nakatani, Masashi; Maksimovic, Srdjan; Baba, Yoshichika et al. (2015) Mechanotransduction in epidermal Merkel cells. Pflugers Arch 467:101-8
Wang, Yuxiang; Marshall, Kara L; Baba, Yoshichika et al. (2015) Compressive viscoelasticity of freshly excised mouse skin is dependent on specimen thickness, strain level and rate. PLoS One 10:e0120897
Walsh, Carolyn M; Bautista, Diana M; Lumpkin, Ellen A (2015) Mammalian touch catches up. Curr Opin Neurobiol 34:133-9
Lesniak, Daine R; Gerling, Gregory J (2014) Mimicking the End Organ Architecture of Slowly Adapting Type I Afferents May Increase the Durability of Artificial Touch Sensors. IEEE Haptics Symp 2014:361-366
Owens, David M; Lumpkin, Ellen A (2014) Diversification and specialization of touch receptors in skin. Cold Spring Harb Perspect Med 4:
Wang, Yuxiang; Gerling, Gregory J (2014) Computational Modeling Reinforces that Proprioceptive Cues May Augment Compliance Discrimination When Elasticity Is Decoupled From Radius of Curvature. Haptics (2014) 2014:360-368

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