Proprioceptive sensitivity to imposed finger deflections.

Hand proprioception, the sense of the posture and movements of the wrist and digits, is critical to dexterous manual behavior and to stereognosis, the ability to sense the three-dimensional structure of objects held in the hand. To better understand this sensory modality and its role in hand function, we sought to characterize the acuity with which the postures and movements of finger joints are sensed. To this end, we measured the ability of human subjects to discriminate changes in posture and speed around the three joints of the index finger. In these experiments, we isolated the sensory component by imposing the postures on an otherwise still hand, to complement other studies in which subjects made judgments on actively achieved postures. We found that subjects could reliably sense 12-16% changes in joint angle and 18-32% changes in joint speed. Furthermore, the acuity for posture and speed was comparable across the three joints of the finger. Finally, task performance was unaffected by the presence of a vibratory stimulus, calling into question the role of cutaneous cues in hand proprioception.NEW & NOTEWORTHY Manual dexterity and stereognosis are supported by two exquisite sensory systems, namely touch and proprioception. Here, we measure the sensitivity of hand proprioception and show that humans can sense the posture and movements of the fingers with great accuracy. We also show that application of a skin vibration does not impair sensitivity, suggesting that proprioceptive acuity relies primarily on receptors in the muscles (and possibly tendons) rather than the skin.

Texture is encoded in precise temporal spiking patterns in primate somatosensory cortex.

Humans are exquisitely sensitive to the microstructure and material properties of surfaces. In the peripheral nerves, texture information is conveyed via two mechanisms: coarse textural features are encoded in spatial patterns of activation that reflect their spatial layout, and fine features are encoded in highly repeatable, texture-specific temporal spiking patterns evoked as the skin moves across the surface. Here, we examined whether this temporal code is preserved in the responses of neurons in somatosensory cortex. We scanned a diverse set of everyday textures across the fingertip of awake macaques while recording the responses evoked in individual cortical neurons. We found that temporal spiking patterns are highly repeatable across multiple presentations of the same texture, with millisecond precision. As a result, texture identity can be reliably decoded from the temporal patterns themselves, even after information carried in the spike rates is eliminated. However, the combination of rate and timing is more informative than either code in isolation. The temporal precision of the texture response is heterogenous across cortical neurons and depends on the submodality composition of their input and on their location along the somatosensory neuraxis. Furthermore, temporal spiking patterns in cortex dilate and contract with decreases and increases in scanning speed, respectively, and this systematic relationship between speed and patterning may contribute to the observed perceptual invariance to speed. Finally, we find that the quality of a texture percept can be better predicted when these temporal patterns are taken into consideration. We conclude that high-precision spike timing complements rate-based signals to encode texture in somatosensory cortex.

Genetic mapping in Diversity Outbred mice identifies a Trpa1 variant influencing late-phase formalin response.

Identification of genetic variants that influence susceptibility to pain is key to identifying molecular mechanisms and targets for effective and safe therapeutic alternatives to opioids. To identify genes and variants associated with persistent pain, we measured late-phase response to formalin injection in 275 male and female Diversity Outbred mice genotyped for over 70,000 single nucleotide polymorphisms. One quantitative trait locus reached genome-wide significance on chromosome 1 with a support interval of 3.1 Mb. This locus, Nociq4 (nociceptive sensitivity quantitative trait locus 4; MGI: 5661503), harbors the well-known pain gene Trpa1 (transient receptor potential cation channel, subfamily A, member 1). Trpa1 is a cation channel known to play an important role in acute and chronic pain in both humans and mice. Analysis of Diversity Outbred founder strain allele effects revealed a significant effect of the CAST/EiJ allele at Trpa1, with CAST/EiJ carrier mice showing an early, but not late, response to formalin relative to carriers of the 7 other inbred founder alleles (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, PWK/PhJ, and WSB/EiJ). We characterized possible functional consequences of sequence variants in Trpa1 by assessing channel conductance, TRPA1-TRPV1 interactions, and isoform expression. The phenotypic differences observed in CAST/EiJ relative to C57BL/6J carriers were best explained by Trpa1 isoform expression differences, implicating a splice junction variant as the causal functional variant. This study demonstrates the utility of advanced, high-precision genetic mapping populations in resolving specific molecular mechanisms of variation in pain sensitivity.

Neural Basis of Touch and Proprioception in Primate Cortex.

The sense of proprioception allows us to keep track of our limb posture and movements and the sense of touch provides us with information about objects with which we come into contact. In both senses, mechanoreceptors convert the deformation of tissues-skin, muscles, tendons, ligaments, or joints-into neural signals. Tactile and proprioceptive signals are then relayed by the peripheral nerves to the central nervous system, where they are processed to give rise to percepts of objects and of the state of our body. In this review, we first examine briefly the receptors that mediate touch and proprioception, their associated nerve fibers, and pathways they follow to the cerebral cortex. We then provide an overview of the different cortical areas that process tactile and proprioceptive information. Next, we discuss how various features of objects-their shape, motion, and texture, for example-are encoded in the various cortical fields, and the susceptibility of these neural codes to attention and other forms of higher-order modulation. Finally, we summarize recent efforts to restore the senses of touch and proprioception by electrically stimulating somatosensory cortex. © 2018 American Physiological Society. Compr Physiol 8:1575-1602, 2018.

Sex and strain influence attribution of incentive salience to reward cues in mice.

The propensity to attribute incentive salience to reward cues, measured by Pavlovian sign-tracking, is strongly associated with addiction-related traits including cocaine self-administration, impulsivity, novelty reactivity, and novelty preference. Despite its critical role in addiction, the genetic underpinnings of incentive salience attribution and its relationship to drug addiction are unknown. Mouse genetics can be a powerful means to discover genetic mechanisms underlying this relationship. However, feasibility of genetic dissection of sign-tracking in mice is unknown as only a single study limited to male C57BL/6J mice has rigorously examined this behavior, and limited sign-tracking was observed. Highly diverse mouse populations such as the Collaborative Cross (CC) and Diversity Outbred population (DO) possess a greater range of behavioral and genetic variation than conventional laboratory strains. In the present study, we evaluated sign-tracking and the related phenotype goal-tracking in mice of both sexes from five inbred CC and DO founder strains. Male CAST/EiJ mice exhibited robust sign-tracking; male NOD, male C57BL/6J, and female A/J mice also exhibited significant sign-tracking. Male and female mice from all strains exhibited significant goal-tracking, and significant strain and sex differences were observed. Sign-tracking in males was genetically correlated with exploration of a novel environment, and heritability of sign-tracking and goal-tracking ranged from .32 to .41. These data highlight the importance of considering genetic diversity when evaluating the occurrence of specific behavioral traits in the laboratory mouse and demonstrate that the CC and DO mouse populations can be used to discover mechanisms underlying genetic relationships among sign-tracking and addiction-related behaviors.