bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dry eye sensitizes cool cells to capsaicin-induced changes in activity via TRPV1
Authors: Hatta Azusa , Kurose Masayuki , Sullivan Cara , Okamoto Keiichiro , Fujii Noritaka , Yamamura Kensuke , Meng Ian D. 
Published: April 2019

Corneal cool cells are sensitive to the ocular fluid status of the corneal surface and may be responsible for the regulation of basal tear production. Previously, we have shown that dry eye, induced by lacrimal gland excision (LGE) in rats, sensitized corneal cool cells to the transient receptor potential melastatin 8 (TRPM8) agonist menthol and to cool stimulation. In the present study, we examined the effect of dry eye on the sensitivity of cool cells to the transient receptor potential vanilloid 1 (TRPV1) agonist capsaicin. Single-unit recordings in the trigeminal ganglion were performed 7–10 days after LGE. At a concentration of 0.3 μM, capsaicin did not affect ongoing or cool-evoked activity in control animals yet facilitated ongoing activity and suppressed cool-evoked activity in LGE animals. At higher concentrations (3 μM), capsaicin continued to facilitate ongoing activity in LGE animals but suppressed ongoing activity in control animals. Higher concentrations of capsaicin also suppressed cool-evoked activity in both groups of animals, with an overall greater effect in LGE animals. In addition to altering cool-evoked activity, capsaicin enhanced the sensitivity of cool cells to heat in LGE animals. Capsaicin-induced changes were prevented by the application of the TRPV1 antagonist capsazepine. With the use of fluorescent in situ hybridization, TRPV1 and TRPM8 expression was examined in retrograde tracer-identified corneal neurons. The coexpression of TRPV1 and TRPM8 in corneal neurons was significantly greater in LGE-treated animals when compared with sham controls. These results indicate that LGE-induced dry eye increases TRPV1-mediated responses in corneal cool cells at least in part through the increased expression of TRPV1. NEW & NOTEWORTHY Corneal cool cells are known to detect drying of the ocular surface. Our study is the first to report that dry eye induced alterations in cool cell response properties, including the increased responsiveness to noxious heat and activation by capsaicin. Along with the changes in cell response properties, it is possible these neurons also function differently in dry eye, relaying information related to the perception of ocular irritation in addition to regulating tearing and blinking.
The contradictory influence of velocity: representational momentum in the tactile modality
Authors: Merz Simon , Deller Julia , Meyerhoff Hauke S. , Spence Charles , Frings Christian 
Published: April 2019

Representational momentum (RM) is the term used to describe a systematic mislocalization of dynamic stimuli, a forward shift; that is, an overestimation of the location of a stimulus along its anticipated trajectory. In the present study, we investigate the effect of velocity on tactile RM, because two distinct and contrasting predictions can be made, based on different theoretical accounts. According to classical accounts of RM, based on numerous visual and auditory RM studies, an increase of the forward shift with increasing target velocity is predicted. In contrast, theoretical accounts explaining spatiotemporal tactile illusions such as the tau or cutaneous rabbit effect predict a decrease of the forward shift with increasing target velocity. In three experiments reported here, a tactile experimental setup modeled on existing RM setups was implemented. Participants indicated the last location of a sequence of three tactile stimuli, which either did or did not imply motion in a consistent direction toward the elbow/wrist. Velocity was manipulated by changing the interstimulus interval as well as the duration of the stimuli. The results reveal that increasing target velocity led to a decrease and even a reversal of the forward shift, resulting in a backward shift. This result is consistent with predictions based on the evidence from tactile spatiotemporal illusions. The theoretical implications of these results for RM are discussed. NEW & NOTEWORTHY This study tests two distinct predictions concerning the influence of velocity on the localization of dynamic tactile stimuli. We demonstrate for tactile stimuli that with increasing velocity, a misperception in the direction of anticipated motion (termed “representational momentum”) turns into a misperception against the direction of motion. This result is in line with predictions based on tactile spatiotemporal illusions but challenges classical theoretical accounts of representational momentum based on evidence from vision and audition.
Case Studies in Neuroscience: The central and somatosensory contributions to finger interdependence and coordination: lessons from a study of a “deafferented person”
Authors: Cuadra Cristian , Falaki Ali , Sainburg Robert , Sarlegna Fabrice R. , Latash Mark L. 
Published: April 2019

We tested finger force interdependence and multifinger force-stabilizing synergies in a patient with large-fiber peripheral neuropathy (“deafferented person”). The subject performed a range of tasks involving accurate force production with one finger and with four fingers. In one-finger tasks, nontask fingers showed unintentional force production (enslaving) with an atypical pattern: very large indices for the lateral (index and little) fingers and relatively small indices for the central (middle and ring) fingers. Indices of multifinger synergies stabilizing total force and of anticipatory synergy adjustments in preparation to quick force pulses were similar to those in age-matched control females. During constant force production, removing visual feedback led to a slow force drift to lower values (by ~25% over 15 s). The results support the idea of a neural origin of enslaving and suggest that the patterns observed in the deafferented person were reorganized based on everyday manipulation tasks. The lack of significant changes in the synergy index shows that synergic control can be organized in the absence of somatosensory feedback. We discuss the control of the hand in deafferented persons within the α-model of the equilibrium-point hypothesis and suggest that force drift results from an unintentional drift of the control variables to muscles toward zero values. NEW & NOTEWORTHY We demonstrate atypical patterns of finger enslaving and unchanged force-stabilizing synergies in a person with large-fiber peripheral neuropathy. The results speak strongly in favor of central origin of enslaving and its reorganization based on everyday manipulation tasks. The data show that synergic control can be implemented in the absence of somatosensory feedback. We discuss the control of the hand in deafferented persons within the α-model of the equilibrium-point hypothesis.
Somatosensory interactions reveal feature-dependent computations
Authors: Rahman M. Shoaibur , Yau Jeffrey M. 
Published: April 2019

Our ability to perceive and discriminate textures is based on the processing of high-frequency vibrations generated on the fingertip as it scans across a surface. Although much is known about the processing of vibration amplitude and frequency information when cutaneous stimulation is experienced at a single location on the body, how these stimulus features are processed when touch occurs at multiple locations is poorly understood. We evaluated participants’ ability to discriminate tactile cues (100–300 Hz) on one hand while they ignored distractor cues experienced on their other hand. We manipulated the relative positions of the hands to characterize how limb position influenced cutaneous touch interactions. In separate experiments, participants judged either the frequency or intensity of mechanical vibrations. We found that vibrations experienced on one hand always systematically modulated the perception of vibrations on the other hand. Notably, bimanual interaction patterns and their sensitivity to hand locations differed according to stimulus feature. Somatosensory interactions in intensity perception were only marked by attenuation that was invariant to hand position manipulations. In contrast, interactions in frequency perception consisted of both bias and sensitivity changes that were more pronounced when the hands were held in close proximity. We implemented models to infer the neural computations that mediate somatosensory interactions in the intensity and frequency dimensions. Our findings reveal obligatory and feature-dependent somatosensory interactions that may be supported by both feature-specific and feature-general operations. NEW & NOTEWORTHY Little is known about the neural computations mediating feature-specific sensory interactions between the hands. We show that vibrations experienced on one hand systematically modulate the perception of vibrations felt on the other hand. Critically, interaction patterns and their dependence on the relative positions of the hands differed depending on whether participants judged vibration intensity or frequency. These results, which we recapitulate with models, imply that somatosensory interactions are mediated by feature-dependent neural computations.
The effects of vibration-induced altered stretch reflex sensitivity on maximal motor unit firing properties
Authors: Barrera-Curiel Alejandra , Colquhoun Ryan J. , Hernandez-Sarabia Jesus A. , DeFreitas Jason M. 
Published: April 2019

It is well known that muscle spindles have a monosynaptic, excitatory connection with α-motoneurons. However, the influence of muscle spindles on human motor unit behavior during maximal efforts remains untested. It has also been shown that muscle spindle function, as assessed by peripheral reflexes, can be systematically manipulated with muscle vibration. Therefore, the purpose of this study was to analyze the effects of brief and prolonged vibration on maximal motor unit firing properties. A crossover design was used, in which each of the 24 participants performed one to three maximal knee extensions under three separate conditions: 1) control, 2) brief vibration that was applied during the contraction, and 3) after prolonged vibration that was applied for ~20 min before the contraction. Multichannel EMG was recorded from the vastus lateralis during each contraction and was decomposed into its constituent motor unit action potential trains. Surprisingly, an approximate 9% reduction in maximal voluntary strength was observed not only after prolonged vibration but also during brief vibration. In addition, both vibration conditions had a large, significant effect on firing rates (a decrease in the rates) and a small to moderate, nonsignificant effect on recruitment thresholds (a small increase in the thresholds). Therefore, vibration had a detrimental influence on both maximal voluntary strength and motor unit firing properties, which we propose is due to altered function of the stretch reflex pathway. NEW & NOTEWORTHY We used vibration to alter muscle spindle function and examined the vibration’s influence on maximal motor unit properties. We discovered that vibration had a detrimental influence on motor unit behavior and motor output by decreasing motor unit firing rates, increasing recruitment thresholds, which led to decreased maximal strength. We believe that understanding the role of muscle spindles during maximal contractions provides a deeper insight into motor control and sensorimotor integration.
Stable memory and computation in randomly rewiring neural networks
Authors: Acker Daniel , Paradis Suzanne , Miller Paul 
Published: April 2019

Our brains must maintain a representation of the world over a period of time much longer than the typical lifetime of the biological components producing that representation. For example, recent research suggests that dendritic spines in the adult mouse hippocampus are transient with an average lifetime of ~10 days. If this is true, and if turnover is equally likely for all spines, ~95% of excitatory synapses onto a particular neuron will turn over within 30 days; however, a neuron’s receptive field can be relatively stable over this period. Here, we use computational modeling to ask how memories can persist in neural circuits such as the hippocampus and visual cortex in the face of synapse turnover. We demonstrate that Hebbian plasticity during replay of presynaptic activity patterns can integrate newly formed synapses into pre-existing memories. Furthermore, we find that Hebbian plasticity during replay is sufficient to stabilize the receptive fields of hippocampal place cells in a model of the grid-cell-to-place-cell transformation in CA1 and of orientation-selective cells in a model of the center-surround-to-simple-cell transformation in V1. Together, these data suggest that a simple plasticity rule, correlative Hebbian plasticity of synaptic strengths, is sufficient to preserve neural representations in the face of synapse turnover, even in the absence of activity-dependent structural plasticity. NEW & NOTEWORTHY Recent research suggests that synapses turn over rapidly in some brain structures; however, memories seem to persist for much longer. We show that Hebbian plasticity of synaptic strengths during reactivation events can preserve memory in computational models of hippocampal and cortical networks despite turnover of all synapses. Our results suggest that memory can be stored in the correlation structure of a network undergoing rapid synaptic remodeling.
Autonomous patch-clamp robot for functional characterization of neurons in vivo: development and application to mouse visual cortex
Authors: Holst Gregory L. , Stoy William , Yang Bo , Kolb Ilya , Kodandaramaiah Suhasa B. , Li Lu , Knoblich Ulf , Zeng Hongkui , Haider Bilal , Boyden Edward S. , Forest Craig R. 
Published: April 2019

Patch clamping is the gold standard measurement technique for cell-type characterization in vivo, but it has low throughput, is difficult to scale, and requires highly skilled operation. We developed an autonomous robot that can acquire multiple consecutive patch-clamp recordings in vivo. In practice, 40 pipettes loaded into a carousel are sequentially filled and inserted into the brain, localized to a cell, used for patch clamping, and disposed. Automated visual stimulation and electrophysiology software enables functional cell-type classification of whole cell-patched cells, as we show for 37 cells in the anesthetized mouse in visual cortex (V1) layer 5. We achieved 9% yield, with 5.3 min per attempt over hundreds of trials. The highly variable and low-yield nature of in vivo patch-clamp recordings will benefit from such a standardized, automated, quantitative approach, allowing development of optimal algorithms and enabling scaling required for large-scale studies and integration with complementary techniques. NEW & NOTEWORTHY In vivo patch-clamp is the gold standard for intracellular recordings, but it is a very manual and highly skilled technique. The robot in this work demonstrates the most automated in vivo patch-clamp experiment to date, by enabling production of multiple, serial intracellular recordings without human intervention. The robot automates pipette filling, wire threading, pipette positioning, neuron hunting, break-in, delivering sensory stimulus, and recording quality control, enabling in vivo cell-type characterization.
Angular vestibuloocular reflex responses in Otop1 mice. I. Otolith sensor input is essential for gravity context-specific adaptation
Authors: Khan Serajul I. , Della Santina Charles C. , Migliaccio Americo A. 
Published: April 2019

The role of the otoliths in mammals in the angular vestibuloocular reflex (VOR) has been difficult to determine because there is no surgical technique that can reliably ablate them without damaging the semicircular canals. The Otopetrin1 (Otop1) mouse lacks functioning otoliths because of failure to develop otoconia but seems to have otherwise normal peripheral anatomy and neural circuitry. By using these animals we sought to determine the role of the otoliths in angular VOR baseline function and adaptation. In six Otop1 mice and six control littermates we measured baseline ocular countertilt about the three primary axes in head coordinates; baseline horizontal (rotation about an Earth-vertical axis parallel to the dorsal-ventral axis) and vertical (rotation about an Earth-vertical axis parallel to the interaural axis) sinusoidal (0.2–10 Hz, 20–100°/s) VOR gain (= eye/head velocity); and the horizontal and vertical VOR after gain-increase (1.5×) and gain-decrease (0.5×) adaptation training. Countertilt responses were significantly reduced in Otop1 mice. Baseline horizontal and vertical VOR gains were similar between mouse types, and so was horizontal VOR adaptation. For control mice, vertical VOR adaptation was evident when the testing context, left ear down (LED) or right ear down (RED), was the same as the training context (LED or RED). For Otop1 mice, VOR adaptation was evident regardless of context. Our results suggest that the otolith translational signal does not contribute to the baseline angular VOR, probably because the mouse VOR is highly compensatory, and does not alter the magnitude of adaptation. However, we show that the otoliths are important for gravity context-specific angular VOR adaptation. NEW & NOTEWORTHY This is the first study examining the role of the otoliths (defined here as the utricle and saccule) in adaptation of the angular vestibuloocular reflex (VOR) in an animal model in which the otoliths are reliably inactivated and the semicircular canals preserved. We show that they do not contribute to adaptation of the normal angular VOR. However, the otoliths provide the main cue for gravity context-specific VOR adaptation.
Angular vestibuloocular reflex responses in Otop1 mice. II. Otolith sensor input improves compensation after unilateral labyrinthectomy
Authors: Khan Serajul I. , Della Santina Charles C. , Migliaccio Americo A. 
Published: April 2019

The role of the otoliths in mammals in the normal angular vestibuloocular reflex (VOR) was characterized in an accompanying study based on the Otopetrin1 (Otop1) mouse, which lacks functioning otoliths because of failure to develop otoconia but seems to have otherwise normal peripheral anatomy and neural circuitry. That study showed that otoliths do not contribute to the normal horizontal (rotation about Earth-vertical axis parallel to dorso-ventral axis) and vertical (rotation about Earth-vertical axis parallel to interaural axis) angular VOR but do affect gravity context-specific VOR adaptation. By using these animals, we sought to determine whether the otoliths play a role in the angular VOR after unilateral labyrinthectomy when the total canal signal is reduced. In five Otop1 mice and five control littermates we measured horizontal and vertical left-ear-down and right-ear-down sinusoidal VOR (0.2–10 Hz, 20–100°/s) during the early (3–5 days) and plateau (28–32 days) phases of compensation after unilateral labyrinthectomy and compared these measurements with baseline preoperative responses from the accompanying study. From similar baselines, acute gain loss was ~25% less in control mice, and chronic gain recovery was ~40% more in control mice. The acute data suggest that the otoliths contribute to the angular VOR when there is a loss of canal function. The chronic data suggest that a unilateral otolith signal can significantly improve angular VOR compensation. These data have implications for vestibular rehabilitation of patients with both canal and otolith loss and the development of vestibular implants, which currently only mimic the canals on one side.NEW & NOTEWORTHY This is the first study examining the role of the otoliths (defined here as the utricle and saccule) on the acute and chronic angular vestibuloocular reflex (VOR) after unilateral labyrinthectomy in an animal model in which the otoliths are reliably inactivated and the semicircular canals preserved. This study shows that the otolith signal is used to augment the acute angular VOR and help boost VOR compensation after peripheral injury.
PLOJDY ANALYSIS AND DNA CONTENT OF MUTANT BANAN "PISANG BERANGAN" USING FLOW CYTOMETRY
Authors: OTHMAN ROFINA YASMIN , SHADIA ABDELGADIR RAYIS , CHAI MAK 
Published: April 2019

Mutagens cause random changes in the nuclear DNA or cytoplasmic organelles, resulting in gene, chromosomal or genomic mutations and hence, create variability. In this study, flow cytometry (FCM) was used to determine ploidy levels and DNA content in gamma-irradiated variants of mutated Pisang Berangan (cv. Intan, AAA) - a local banana genotype. Induced variants such as short plant stature (stunted growth), late flowering plants (late maturity) and abnormalities in bunch characters were selected to study possible changes at the DNA level. The study showed that DNA content of mutated plants differed from non-irradiated control and that irradiation had the most effect at high doses (40 and 60 Gy). The increase of DNA content in 20 Gy and 30 Gy treated plants was not more than that of the control plants. The values of genomic DNA content of gamma-irradiation variants decreased as the dose of irradiation increased from 20 to 60 Gy, indicating that the high dose of gamma-irradiation had a significant effect on the genome of the plants. The analysis further showed that phenotypic variation due to mutagenesis was reflected in the DNA content of the plants. The results also showed that ploidy levels were not affected by gamma-irradiation even at high doses. Keywords: Musa spp./mutation breeding/ flow cytometry/Â ploidy level/ DNA content
Sacubitril/Valsartan Decreases Cardiac Fibrosis in Left Ventricle Pressure Overload by Restoring PKG Signaling in Cardiac Fibroblasts
Authors: Burke Ryan M. , Lighthouse Janet K. , Mickelsen Deanne M. , Small Eric M. 
Published: April 2019

Background
Heart failure (HF) is invariably accompanied by development of cardiac fibrosis, a form of scarring that increases muscular tissue rigidity and decreases cardiac contractility. Cardiac fibrosis arises from a pathological attempt to repair tissue damaged during maladaptive remodeling. Treatment options to block or reverse fibrosis have proven elusive. Neprilysin is an endopeptidase that degrades vasoactive peptides, including atrial natriuretic peptide. Thus, neprilysin inhibition reduces hypertension, ultimately limiting maladaptive cardiac remodeling. LCZ696, which consists of an angiotensin receptor blocker (valsartan [VAL]) and a neprilysin inhibitor (sacubitril [SAC]), was shown to be well tolerated and significantly reduced the risk of death and hospitalization in HF patients with reduced ejection fraction. We hypothesized that SAC/VAL directly inhibits fibroblast activation and development of pathological fibrosis.

Methods and Results
We used a mouse model of left ventricle pressure overload coupled to in vitro studies in primary mouse and human cardiac fibroblasts (CFs) to study the impact of SAC/VAL on CF activation and cardiac fibrosis. SAC/VAL significantly ameliorated pressure overload–induced cardiac fibrosis by blocking CF activation and proliferation, leading to functional improvement. Mechanistically, the beneficial impact of SAC/VAL at least partially stemmed from restoration of PKG (protein kinase G) signaling in HF patient-derived CF, which inhibited Rho activation associated with myofibroblast transition.

Conclusions
This study reveals that SAC/VAL acts directly on CF to prevent maladaptive cardiac fibrosis and dysfunction during pressure overload–induced hypertrophy and suggests that SAC/VAL should be evaluated as a direct antifibrotic therapeutic for conditions such as HF with preserved ejection fraction.