Biology subjects

Gerling, G. J.

Publications and source records attributed to Gerling, G. J..

5 recordsLinked to original sources

bioRxiv2023

PIEZO2-dependent rapid pain system in humans and mice.

The PIEZO2 ion channel is critical for transducing light touch into neural signals but is not considered necessary for transducing acute pain in humans. Here, we discovered an exception - a form of mechanical pain evoked by hair pulling. Based on observations in a rare group of individuals with PIEZO2 deficiency syndrome, we demonstrated that hair-pull pain is dependent on PIEZO2 transduction. Studies in control participants showed that hair-pull pain triggered a distinct nocifensive response, including a nociceptive reflex. Observations in rare A{beta} deafferented individuals and nerve conduction block studies in control participants revealed that hair-pull pain perception is dependent on A{beta} input. Single-unit axonal recordings revealed that a class of cooling-responsive myelinated nociceptors in human skin is selectively tuned to painful hair-pull stimuli. Further, we pharmacologically mapped these nociceptors to a specific transcriptomic class. Finally, using functional imaging in mice, we demonstrated that in a homologous nociceptor, Piezo2 is necessary for high-sensitivity, robust activation by hair-pull stimuli. Together, we have demonstrated that hair-pulling evokes a distinct type of pain with conserved behavioral, neural, and molecular features across humans and mice.

neuroscience↗

bioRxiv2023

Mechanoreceptive Aβ primary afferents discriminate naturalistic social touch inputs at a functionally relevant time scale

Interpersonal touch is an important part of our social and emotional interactions. How these physical, skin-to-skin touch expressions are processed in the peripheral nervous system is not well understood. From single-unit microneurography recordings in humans, we evaluated the capacity of six subtypes of cutaneous afferents to differentiate perceptually distinct social touch expressions. By leveraging conventional statistical analyses and classification analyses using convolutional neural networks and support vector machines, we found that single units of multiple A{beta} subtypes, especially slowly adapting type II (SA-II) and fast adapting hair follicle afferents (HFA), can reliably differentiate the skin contact of those expressions at accuracies similar to those perceptually. Rapidly adapting field (Field) afferents exhibit lower accuracies, whereas C-tactile (CT), fast adapting Pacinian corpuscles (FA-II), and muscle spindle (MS) afferents can barely differentiate the expressions, despite responding to the stimuli. We then identified the most informative firing patterns of SA-II and HFA afferents spike trains, which indicate that an average duration of 3-4 s of firing provides sufficient discriminative information. Those two subtypes also exhibit robust tolerance to shifts in spike-timing of up to 10 ms. A greater shift in spike-timing, however, drastically compromises an afferents discrimination capacity, and can change a firing patterns envelope to resemble that of another expression. Altogether, the findings indicate that SA-II and HFA afferents differentiate the skin contact of social touch at time scales relevant for such interactions, which is 1-2 orders of magnitude longer than those relevant for discriminating non-social touch inputs.

neuroscience↗

bioRxiv2023

An individual's skin stiffness predicts their tactile acuity

Individual differences in tactile acuity have been correlated with age, gender, and finger size, while the role of the skins stiffness has been underexplored. Using an approach to image the 3- D deformation of the skin surface while in contact with transparent elastic objects, we evaluate a cohort of 40 young participants, who present a diverse range of finger size, skin stiffness, and fingerprint ridge breadth. The results indicate that skin stiffness generally correlates with finger size, although individuals with relatively softer skin can better discriminate compliant objects. Analysis of contact at the skin surface reveals that softer skin generates more prominent patterns of deformation, in particular greater rates of change in contact area, which correlate with higher rates of perceptual discrimination, regardless of finger size. Moreover, upon applying hyaluronic acid to soften individuals skin, we observe immediate, marked and systematic changes in skin deformation and consequent improvements in perceptual acuity. Together, the combination of 3- D imaging of the skin surface, biomechanics measurements, multivariate regression and clustering, and psychophysical experiments show that subtle distinctions in skin stiffness modulate the mechanical signaling of touch and shape individual differences in perceptual acuity. Key points described in the manuscriptO_LIWhile declines in tactile acuity with aging are a function of multiple factors, for younger people the current working hypothesis has been that smaller fingers are better at informing perceptual discrimination due to a higher density of neural afferents. C_LIO_LITo decouple relative impacts on tactile acuity of skin properties of finger size, skin stiffness, and fingerprint ridge breadth, we combined 3D imaging of skin surface deformation, biomechanical measurements, multivariate regression and clustering, and psychophysics. C_LIO_LIThe results indicate skin stiffness generally correlates with finger size, although more robustly correlates with and predicts an individuals perceptual acuity. C_LIO_LIIn particular, more elastic skin generates higher rates of deformation, which correlate with perceptual discrimination, shown most dramatically by softening each participants skin with hyaluronic acid. C_LIO_LIIn refining the current working hypothesis, we show the skins stiffness strongly shapes the signaling of touch and modulates individual differences in perceptual acuity. C_LI

neuroscience↗

bioRxiv2022

In vivo calcium imaging identifies functionally and molecularly distinct subsets of tongue-innervating mechanosensory neurons

Mechanosensory neurons in the mouth provide essential information to guide feeding and speech. How classes of oral mechanoreceptors contribute to oral behaviors is not well understood; in particular, the functional properties of lingual mechanoreceptors remain elusive. Previous work identified putative mechanosensory endings in the tongue with novel morphologies; how these fit into current knowledge of mechanosensory neuron classification is not known. To identify functional classes of lingual mechanosensory neurons, we used in vivo calcium imaging of trigeminal ganglia. We first investigated calcium responses of tongue-innervating trigeminal neurons to thermal and mechanical stimulation (e.g., pressure, fluid flow, temperature changes). We found that around 17% of neurons responded to pressure, and that these pressure responders were significantly larger than neurons that only responded to temperature changes. To further investigate the cadre of functionally distinct mechanosensory neurons, we tested responses to brushing and sustained pressures and found that brush-sensitive neurons comprise the majority of tongue-innervating mechanosensory trigeminal neurons. Qualitatively, mechanosensory neurons responded to pressure with distinct kinetics, suggesting the presence of multiple classes of mechanoreceptors. To determine the number of classes, we developed an unbiased multi-layer hierarchical clustering approach to classify calcium response characteristics to pressure stimulation. This approach revealed that mechanosensory neurons displayed five distinct stimulus-response profiles to pressure. Classes include neuronal populations with sustained, transient, high-threshold, and negative responses to force as well as neurons that responded only to brushing. Analysis of cluster representation in transgenic animals with only subsets of labeled neurons reveals molecular markers of clusters and end organ structures. These studies are amongst the first to determine the functional properties of low-threshold mechanosensory neurons innervating the mouse tongue.

neuroscience↗

bioRxiv2020

An elasticity-curvature illusion decouples cutaneous and proprioceptive cues in active exploration of soft objects

Our sense of touch helps us encounter the richness of our natural world. Across a myriad of contexts and repetitions, we have learned to deploy certain exploratory movements in order to elicit perceptual cues that are optimal and efficient. Such cues help us assess an objects roughness, or stickiness, or as in this case, its softness. Leveraging empirical experiments combined with computational modeling of skin deformation, we develop a perceptual illusion for softness, or compliance, where small-compliant and large-stiff spheres are indiscriminable. The elasticity-curvature illusion, however, becomes readily discriminable when explored volitionally. This tactile illusion is unique because it naturally decouples proprioceptive cues from those involving identical, cutaneous contact attributes. Furthermore, the illusion sheds light into exactly how we explore soft objects, i.e., by volitionally controlling force, to optimally elicit and integrate proprioceptive cues amidst illusory cutaneous contact.

neuroscience↗