Meis1 Regulates Nociceptor Development and Behavioral Response to Tactile Stimuli.
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ABSTRACT:
SUBMITTER: Cao Z
PROVIDER: S-EPMC9301487 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Tactile stimuli can be distinguished based on their temporal features (e.g., duration, local frequency, and number of pulses), which are fundamental for vibrotactile frequency perception. Characterizing how the hemodynamic response changes in shape across experimental conditions is important for designing and interpreting fMRI studies on tactile information processing. In this study, we focused on periodic tactile stimuli with different temporal structures and explored the hemodynamic response function (HRF) induced by these stimuli. We found that HRFs were stimulus-dependent in tactile-related brain areas. Continuous stimuli induced a greater area of activation and a stronger and narrower hemodynamic response than intermittent stimuli with the same duration. The magnitude of the HRF increased with increasing stimulus duration. By normalizing the characteristics into topographic matrix, nonlinearity was obvious. These results suggested that stimulation patterns and duration within a cycle may be key characters for distinguishing different stimuli. We conclude that different temporal structures of tactile stimuli induced different HRFs, which are essential for vibrotactile perception and should be considered in fMRI experimental designs and analyses.
| S-EPMC7814760 | biostudies-literature
Project description:BackgroundNociception evokes a rapid withdrawal behavior designed to protect the animal from potential danger. C. elegans performs a reflexive reversal or forward locomotory response when presented with noxious stimuli at the head or tail, respectively. Here, we have developed an assay with precise spatial and temporal control of an infrared laser stimulus that targets one-fifth of the worm's body and quantifies multiple aspects of the worm's escape response.ResultsWhen stimulated at the head, we found that the escape response can be elicited by changes in temperature as small as a fraction of a degree Celsius, and that aspects of the escape behavior such as the response latency and the escape direction change advantageously as the amplitude of the noxious stimulus increases. We have mapped the behavioral receptive field of thermal nociception along the entire body of the worm, and show a midbody avoidance behavior distinct from the head and tail responses. At the midbody, the worm is sensitive to a change in the stimulus location as small as 80 ?m. This midbody response is probabilistic, producing either a backward, forward or pause state after the stimulus. The distribution of these states shifts from reverse-biased to forward-biased as the location of the stimulus moves from the middle towards the anterior or posterior of the worm, respectively. We identified PVD as the thermal nociceptor for the midbody response using calcium imaging, genetic ablation and laser ablation. Analyses of mutants suggest the possibility that TRPV channels and glutamate are involved in facilitating the midbody noxious response.ConclusionThrough high resolution quantitative behavioral analysis, we have comprehensively characterized the C. elegans escape response to noxious thermal stimuli applied along its body, and found a novel midbody response. We further identified the nociceptor PVD as required to sense noxious heat at the midbody and can spatially differentiate localized thermal stimuli.
| S-EPMC3703451 | biostudies-literature
Project description:Study objectivesActigraphy, the tool of choice for assessment of sleep phase disorders, is insensitive to movement-free waking. This study aimed to determine whether the detection of waking could be performed by recording instrumental responses to haptic stimuli delivered by a low-cost device.MethodsTwenty adults underwent 2 nights of laboratory polysomnography (PSG) while wearing a fingerless glove under which a stimulating actigraph ("Wakemeter") was apposed to the palm. The Wakemeter, controlled by a tablet computer, delivered gentle, haptic stimuli every 10 minutes during the sleep period. If a stimulus was detected, the participant squeezed the Wakemeter. Stimulus times, response times and movements were streamed to the tablet. Concurrent PSG data were scored blind to stimuli and responses. Self-reported sleep quality ratings were collected each morning.ResultsThe Wakemeter was acceptable to 19 of 20 participants, and effects on self-reported and objective sleep were small. The probability of a response to the stimulus during a wake epoch was high regardless of movement. In contrast, actigraphy magnitude distributions were indistinguishable across epochs scored wake without movement versus sleep, confirming a known limitation of actigraphy. A simple method for calculating sleep efficiency from responses to the stimuli yielded estimates that were highly correlated with PSG-derived estimates (rho = .69, P < .001).ConclusionsBehavioral responses to haptic stimuli detected epochs of movement-free wake during the sleep period and may augment actigraphy in the low-burden estimation of sleep efficiency. Acceptability of the method over longer recording periods remains to be established.
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Project description:For a comprehensive understanding of the environment, the brain must constantly decide whether the incoming information originates from the same source and needs to be integrated into a coherent percept. This integration process is believed to be mediated by temporal integration windows. If presented with temporally asynchronous stimuli for a few minutes, the brain adapts to this new temporal relation by recalibrating the temporal integration windows. Such recalibration can occur even more rapidly after exposure to just a single trial of asynchronous stimulation. While rapid recalibration has been demonstrated for audio-visual stimuli, evidence for rapid recalibration of visuo-tactile stimuli is lacking. Here, we investigated rapid recalibration in the visuo-tactile domain. Subjects received visual and tactile stimuli with different stimulus onset asynchronies (SOA) and were asked to report whether the visuo-tactile stimuli were presented simultaneously. Our results demonstrate visuo-tactile rapid recalibration by revealing that subjects' simultaneity reports were modulated by the temporal order of stimulation in the preceding trial. This rapid recalibration effect, however, was only significant if the SOA in the preceding trial was smaller than 100 ms, while rapid recalibration could not be demonstrated for SOAs larger than 100 ms. Since rapid recalibration in the audio-visual domain has been demonstrated for SOAs larger than 100 ms, we propose that visuo-tactile recalibration works at shorter SOAs, and thus faster time scales than audio-visual rapid recalibration.
| S-EPMC5809529 | biostudies-literature
Project description:Although stereotypic behaviors are a common problem in captive animals, why certain individuals are more prone to develop them remains elusive. In horses, individuals show considerable differences in how they perceive and react to external events, suggesting that this may partially account for the emergence of stereotypies in this species. In this study, we focused on crib-biting, the most common stereotypy displayed by horses. We compared how established crib-biters ("CB" = 19) and normal controls ("C" = 18) differed in response to a standard "personality" assessment test battery, i.e., reactivity to humans, tactile sensitivity, social reactivity, locomotor activity, and curiosity vs. fearfulness (both in novel and suddenness situations). Our analyses showed that crib-biters only differed from control horses in their tactile sensitivity, suggesting an elevated sensitivity to tactile stimuli. We suggest that this higher tactile sensitivity could be due to altered dopamine or endogenous opioid physiology, resulting from chronic stress exposition. We discuss these findings in relation to the hypothesis that there may be a genetic predisposition for stereotypic behavior in horses, and in relation to current animal husbandry and management practices.
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Project description:The human hand can detect both form and texture information of a contact surface. The detection of skin displacement (sustained stimulus) and changes in skin displacement (transient stimulus) are thought to be mediated in different tactile channels; however, tactile form perception may use both types of information. Here, we studied whether both the temporal frequency and the temporal coherency information of tactile stimuli encoded in sensory neurons could be used to recognize the form of contact surfaces. We used the fishbone tactile illusion (FTI), a known tactile phenomenon, as a probe for tactile form perception in humans. This illusion typically occurs with a surface geometry that has a smooth bar and coarse textures in its adjacent areas. When stroking the central bar back and forth with a fingertip, a human observer perceives a hollow surface geometry even though the bar is physically flat. We used a passive high-density pin matrix to extract only the vertical information of the contact surface, suppressing tangential displacement from surface rubbing. Participants in the psychological experiment reported indented surface geometry by tracing over the FTI textures with pin matrices of the different spatial densities (1.0 and 2.0 mm pin intervals). Human participants reported that the relative magnitude of perceived surface indentation steeply decreased when pins in the adjacent areas vibrated in synchrony. To address possible mechanisms for tactile form perception in the FTI, we developed a computational model of sensory neurons to estimate temporal patterns of action potentials from tactile receptive fields. Our computational data suggest that (1) the temporal asynchrony of sensory neuron responses is correlated with the relative magnitude of perceived surface indentation and (2) the spatiotemporal change of displacements in tactile stimuli are correlated with the asynchrony of simulated sensory neuron responses for the fishbone surface patterns. Based on these results, we propose that both the frequency and the asynchrony of temporal activity in sensory neurons could produce tactile form perception.
| S-EPMC8175693 | biostudies-literature
Project description:The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation. However, this regenerative capacity is lost by postnatal day 7 and the mechanisms of cardiomyocyte cell cycle arrest remain unclear. The homeodomain transcription factor Meis1 is required for normal cardiac development but its role in cardiomyocytes is unknown. Here we identify Meis1 as a critical regulator of the cardiomyocyte cell cycle. Meis1 deletion in mouse cardiomyocytes was sufficient for extension of the postnatal proliferative window of cardiomyocytes, and for re-activation of cardiomyocyte mitosis in the adult heart with no deleterious effect on cardiac function. In contrast, overexpression of Meis1 in cardiomyocytes decreased neonatal myocyte proliferation and inhibited neonatal heart regeneration. Finally, we show that Meis1 is required for transcriptional activation of the synergistic CDK inhibitors p15, p16 and p21. These results identify Meis1 as a critical transcriptional regulator of cardiomyocyte proliferation and a potential therapeutic target for heart regeneration.
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Project description:Transcriptional alterations are characteristic of persistent pain states but the key regulators remain elusive. Using a conditional knockout (cKO) strategy in mice we sought to determine whether loss of the transcriptional co-repressor histone deacetylase four (HDAC4) would have implications for sensory neuron transcription and nociception. HDAC4 was found to be largely dispensable for transcriptional regulation of naïve sensory neurons but was required for transcriptional responses after injury, with Calca and Trpv1 expression consistently downregulated in HDAC4 cKO compared to littermate controls (0.2-0.44 fold). This downregulation corresponded to reduced sensitivity to capsaicin in vitro (76% +/- 4.4% wildtype capsaicin responders vs 56.9% +/- 4.7% cKO responders) and to reduced thermal hypersensitivity in the complete Freund’s adjuvant model of inflammatory pain (1.3-1.4 fold improvement). These data indicate that HDAC4 is a novel inflammatory pain mediator and may be a good therapeutic target, capable of orchestrating the regulation of multiple downstream effectors. Total RNA was extracted from HDAC4 cKO and HDAC4 fl/fl naïve adult lumbar dorsal root ganglia (n=3/group). mRNA expression was compared using Affymetrix Mouse Gene Arrays (Mouse Gene 2.0ST) run on a GeneChip Fluidics Station 450. Chips were scanned on an Affymetrix GeneChip Scanner.
2015-04-23 | E-GEOD-62405 | biostudies-arrayexpress
Project description:Foot-sole somatosensory impairment is a main contributor to balance decline and falls in aging and disease. The cortical networks involved in walking-related foot sole somatosensation, however, remain poorly understood. We thus created and tested a novel MRI-compatible device to enable study of the cortical response to pressure stimuli applied to the foot sole that mimic those stimuli experienced when walking. The device consists of a dual-drive stimulator equipped with two pneumatic cylinders, which are separately programed to apply pressure waveforms to the entire foot sole. In a sample of nine healthy younger adults, the pressure curve applied to the foot sole closely correlated with that experienced during over ground walking (r = 0.811 ± 0.043, P < 0.01). MRI compatibility testing indicated that the device has no or negligible impact on MR image quality. Gradient-recalled echo-planar images of nine healthy young adults using a block-designed 3.5-min walking-related stimulation revealed significant activation within the supplementary motor area, supramarginal gyrus, paracingulate gyri, insula, precentral gyrus, middle temporal gyrus, and hippocampus (uncorrected P < 0.001, k ≥ 10). Together, these results indicate that this stimulation system is MRI-compatible and capable of mimicking walking-related pressure waveforms on foot sole. It may thus be used as a research tool to identify cortical targets for interventions (e.g., non-invasive brain stimulation) aimed at enhancing this important source of input to the locomotor control system.
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Project description:Altered multisensory integration has been reported in autism; however, little is known concerning how the autistic brain processes spatio-temporal information concerning tactile stimuli. We report a study in which a crossed-hands illusion was investigated in autistic children. Neurotypical individuals often experience a subjective reversal of temporal order judgments when their hands are stimulated while crossed, and the illusion is known to be acquired in early childhood. However, under those conditions where the somatotopic representation is given priority over the actual spatial location of the hands, such reversals may not occur. Here, we showed that a significantly smaller illusory reversal was demonstrated in autistic children than in neurotypical children. Furthermore, in an additional experiment, the young boys who had higher Autism Spectrum Quotient (AQ) scores generally showed a smaller crossed hands deficit. These results suggest that rudimentary spatio-temporal processing of tactile stimuli exists in autistic children, and the altered processing may interfere with the development of an external frame of reference in real-life situations.
| S-EPMC4124471 | biostudies-other