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Biomolecules Apr 2023Peripheral nerve injury (PNI) is a health problem that affects many people worldwide. This study is the first to evaluate the potential effect of bee venom (BV) and its...
Peripheral nerve injury (PNI) is a health problem that affects many people worldwide. This study is the first to evaluate the potential effect of bee venom (BV) and its major components in a model of PNI in the mouse. For that, the BV used in this study was analyzed using UHPLC. All animals underwent a distal section-suture of facial nerve branches, and they were randomly divided into five groups. Group 1: injured facial nerve branches without any treatment. Group 2: the facial nerve branches were injured, and the normal saline was injected similarly as in the BV-treated group. Group 3: injured facial nerve branches with local injections of BV solution. Group 4: injured facial nerve branches with local injections of a mixture of PLA2 and melittin. Group 5: injured facial nerve branches with local injection of betamethasone. The treatment was performed three times a week for 4 weeks. The animals were submitted to functional analysis (observation of whisker movement and quantification of nasal deviation). The vibrissae muscle re-innervation was evaluated by retrograde labeling of facial motoneurons in all experimental groups. UHPLC data showed 76.90 ± 0.13%, 11.73 ± 0.13%, and 2.01 ± 0.01%, respectively, for melittin, phospholipase A2, and apamin in the studied BV sample. The obtained results showed that BV treatment was more potent than the mixture of PLA2 and melittin or betamethasone in behavioral recovery. The whisker movement occurred faster in BV-treated mice than in the other groups, with a complete disappearance of nasal deviation two weeks after surgery. Morphologically, a normal fluorogold labeling of the facial motoneurons was restored 4 weeks after surgery in the BV-treated group, but no such restoration was ever observed in other groups. Our findings indicate the potential of the use of BV injections to enhance appropriate functional and neuronal outcomes after PNI.
Topics: Animals; Mice; Bee Venoms; Betamethasone; Facial Nerve Injuries; Melitten; Phospholipases A2
PubMed: 37189427
DOI: 10.3390/biom13040680 -
Current Biology : CB May 2023Cortical activity patterns occupy a small subset of possible network states. If this is due to intrinsic network properties, microstimulation of sensory cortex should...
Cortical activity patterns occupy a small subset of possible network states. If this is due to intrinsic network properties, microstimulation of sensory cortex should evoke activity patterns resembling those observed during natural sensory input. Here, we use optical microstimulation of virally transfected layer 2/3 pyramidal neurons in the mouse primary vibrissal somatosensory cortex to compare artificially evoked activity with natural activity evoked by whisker touch and movement ("whisking"). We find that photostimulation engages touch- but not whisking-responsive neurons more than expected by chance. Neurons that respond to photostimulation and touch or to touch alone exhibit higher spontaneous pairwise correlations than purely photoresponsive neurons. Exposure to several days of simultaneous touch and optogenetic stimulation raises both overlap and spontaneous activity correlations among touch and photoresponsive neurons. We thus find that cortical microstimulation engages existing cortical representations and that repeated co-presentation of natural and artificial stimulation enhances this effect.
Topics: Mice; Animals; Somatosensory Cortex; Parietal Lobe; Movement; Touch; Touch Perception; Vibrissae
PubMed: 37130521
DOI: 10.1016/j.cub.2023.03.085 -
Current Biology : CB May 2023The breathing rhythm serves as a reference that paces orofacial motor actions and orchestrates active sensing. Past work has reported that pacing occurs solely at a...
The breathing rhythm serves as a reference that paces orofacial motor actions and orchestrates active sensing. Past work has reported that pacing occurs solely at a fixed phase relative to sniffing. We re-evaluated this constraint as a function of exploratory behavior. Allocentric and egocentric rotations of the head and the electromyogenic activity of the motoneurons for head and orofacial movements were recorded in free-ranging rats as they searched for food. We found that a change in state from foraging to rearing is accompanied by a large phase shift in muscular activation relative to sniffing, and a concurrent change in the frequency of sniffing, so that pacing now occurs at one of the two phases. Further, head turning is biased such that an animal gathers a novel sample of its environment upon inhalation. In total, the coordination of active sensing has a previously unrealized computational complexity. This can emerge from hindbrain circuits with fixed architecture and credible synaptic time delays.
Topics: Rats; Animals; Vibrissae; Movement; Exploratory Behavior; Rhombencephalon; Motor Neurons; Head Movements
PubMed: 37105167
DOI: 10.1016/j.cub.2023.04.008 -
Cell Reports May 2023Cross-modal plasticity is the repurposing of brain regions associated with deprived sensory inputs to improve the capacity of other sensory modalities. The functional...
Cross-modal plasticity is the repurposing of brain regions associated with deprived sensory inputs to improve the capacity of other sensory modalities. The functional mechanisms of cross-modal plasticity can indicate how the brain recovers from various forms of injury and how different sensory modalities are integrated. Here, we demonstrate that rewiring of the microglia-mediated local circuit synapse is crucial for cross-modal plasticity induced by visual deprivation (monocular deprivation [MD]). MD relieves the usual inhibition of functional connectivity between the somatosensory cortex and secondary lateral visual cortex (V2L). This results in enhanced excitatory responses in V2L neurons during whisker stimulation and a greater capacity for vibrissae sensory discrimination. The enhanced cross-modal response is mediated by selective removal of inhibitory synapse terminals on pyramidal neurons by the microglia in the V2L via matrix metalloproteinase 9 signaling. Our results provide insights into how cortical circuits integrate different inputs to functionally compensate for neuronal damage.
Topics: Animals; Microglia; Neurons; Synapses; Pyramidal Cells; Visual Cortex; Neuronal Plasticity; Vibrissae; Somatosensory Cortex
PubMed: 37086724
DOI: 10.1016/j.celrep.2023.112383 -
PloS One 2023Throughout the last decades, understanding the neural mechanisms of sensory processing has been a key objective for neuroscientists. Many studies focused on uncovering...
Throughout the last decades, understanding the neural mechanisms of sensory processing has been a key objective for neuroscientists. Many studies focused on uncovering the microcircuit-level architecture of somatosensation using the rodent whisker system as a model. Although these studies have significantly advanced our understanding of tactile processing, the question remains to what extent the whisker system can provide results translatable to the human somatosensory system. To address this, we developed a restrained vibrotactile detection task involving the limb system in mice. A vibrotactile stimulus was delivered to the hindlimb of head-fixed mice, who were trained to perform a Go/No-go detection task. Mice were able to learn this task with satisfactory performance and with reasonably short training times. In addition, the task we developed is versatile, as it can be combined with diverse neuroscience methods. Thus, this study introduces a novel task to study the neuron-level mechanisms of tactile processing in a system other than the more commonly studied whisker system.
Topics: Mice; Humans; Animals; Touch; Touch Perception; Hindlimb; Vibrissae; Lower Extremity; Somatosensory Cortex
PubMed: 37079581
DOI: 10.1371/journal.pone.0284735 -
Brain and Behavior May 2023Autism spectrum disorder is a developmental disorder that can affect sensory-motor behaviors in the valproic acid (Val) rodent model of autism. Although whisker...
INTRODUCTION
Autism spectrum disorder is a developmental disorder that can affect sensory-motor behaviors in the valproic acid (Val) rodent model of autism. Although whisker deprivation (WD) induces plastic changes in the cortical neurons, tactile stimulation (TS) during the neonatal period may reverse it. Here, we investigate the interaction effects of TS and WD on behavioral and histologic features of barrel cortex neurons in juvenile Val-treated.
METHODS
Control (CTL, CTL-TS, CTL-WD, and CTL-TS-WD groups) and Val-treated (Val, Val-TS, Val-WD, and Val-TS-WD groups) rats of both sexes were subjected to behavioral tests of social interaction, and novel texture recognition, and Nissl staining. The TS groups were exposed to sensory stimulation for 15 min, three times/day; moreover, all whiskers in the WD groups were trimmed every other day from postnatal days 1 to 21.
RESULTS
Both prenatal valproic acid administration and postnatal WD decreased the rats' performance percentage of the Val and CTL-WD groups of both sexes compared with the CTL groups in the social interaction and texture discrimination tests. Following TS, the performance of the Val-TS-WD group increased significantly compared to the Val group (p < .05), whereas the performance of the CTL-TS-WD group rescued to the CTL group. Nissl staining results also revealed the neuron degeneration percentage in the barrel field area of the Val and CTL-WD groups was increased significantly (p < .05) compared with the CTL group. In this regard, TS decreased the neuron degeneration percentage of the Val-TS-WD and the CTL-TS-WD groups, compared with the CTL group, significantly (p < .05).
CONCLUSION
TS in juvenile male and female rats can act as a modulator and compensate for the behavioral and histological consequences of WD and prenatal valproic acid exposure.
Topics: Pregnancy; Rats; Animals; Male; Female; Autistic Disorder; Social Interaction; Vibrissae; Valproic Acid; Autism Spectrum Disorder; Somatosensory Cortex
PubMed: 37062939
DOI: 10.1002/brb3.2993 -
Nature Communications Apr 2023Suppressing responses to distractor stimuli is a fundamental cognitive function, essential for performing goal-directed tasks. A common framework for the neuronal...
Suppressing responses to distractor stimuli is a fundamental cognitive function, essential for performing goal-directed tasks. A common framework for the neuronal implementation of distractor suppression is the attenuation of distractor stimuli from early sensory to higher-order processing. However, details of the localization and mechanisms of attenuation are poorly understood. We trained mice to selectively respond to target stimuli in one whisker field and ignore distractor stimuli in the opposite whisker field. During expert task performance, optogenetic inhibition of whisker motor cortex increased the overall tendency to respond and the detection of distractor whisker stimuli. Within sensory cortex, optogenetic inhibition of whisker motor cortex enhanced the propagation of distractor stimuli into target-preferring neurons. Single unit analyses revealed that whisker motor cortex (wMC) decorrelates target and distractor stimulus encoding in target-preferring primary somatosensory cortex (S1) neurons, which likely improves selective target stimulus detection by downstream readers. Moreover, we observed proactive top-down modulation from wMC to S1, through the differential activation of putative excitatory and inhibitory neurons before stimulus onset. Overall, our studies support a contribution of motor cortex to sensory selection, in suppressing behavioral responses to distractor stimuli by gating distractor stimulus propagation within sensory cortex.
Topics: Mice; Animals; Somatosensory Cortex; Motor Cortex; Parietal Lobe; Neurons; Vibrissae
PubMed: 37055425
DOI: 10.1038/s41467-023-37848-4 -
Neuroscience and Biobehavioral Reviews Jun 2023Since the discovery 50 years ago of the precisely ordered representation of the whiskers in somatosensory cortex, the rodent tactile sensory system has been a fertile... (Review)
Review
Since the discovery 50 years ago of the precisely ordered representation of the whiskers in somatosensory cortex, the rodent tactile sensory system has been a fertile ground for the study of sensory processing. With the growing sophistication of touch-based behavioral paradigms, together with advances in neurophysiological methodology, a new approach is emerging. By posing increasingly complex perceptual and memory problems, in many cases analogous to human psychophysical tasks, investigators now explore the operations underlying rodent problem solving. We define the neural basis of tactile cognition as the transformation from a stage in which neuronal activity encodes elemental features, local in space and in time, to a stage in which neuronal activity is an explicit representation of the behavioral operations underlying the current task. Selecting a set of whisker-based behavioral tasks, we show that rodents achieve high level performance through the workings of neuronal circuits that are accessible, decodable, and manipulatable. As a means towards exploring tactile cognition, this review presents leading psychophysical paradigms and, where known, their neural correlates.
Topics: Animals; Humans; Touch; Rodentia; Touch Perception; Somatosensory Cortex; Cognition
PubMed: 37028580
DOI: 10.1016/j.neubiorev.2023.105161 -
Biomedicine & Pharmacotherapy =... May 2023GPR40 is found primarily in pancreatic β cells, and is well known to regulate insulin secretion. Despite numerous studies on GPR40, the role and functions of GPR40...
GPR40 is found primarily in pancreatic β cells, and is well known to regulate insulin secretion. Despite numerous studies on GPR40, the role and functions of GPR40 related to hair growth are not yet known. The current study investigated hair growth promoting effect of the GPR40 agonists and its mechanism of action using various bio-informatics tools, in vitro and animal experiments. GPR40 may affect the hair cycle, according to clustering and Gene Set Enrichment Analysis (GSEA). Hair growth effect of GPR40 was validated by telogen-to-anagen transition and vibrissae organ culture in the mouse. GPR40 was predominantly expressed in the outer root sheath (ORS) in anagen stage, suggesting that ORS cell is the target of GPR40 agonists. To investigate the mechanism of action for GPR40 agonists' hair growth effect, Gene Ontology (GO) enrichment analysis was performed and it revealed that GPR40 agonists were associated with angiogenesis. ANGPTL4, known for promoting angiogenesis, was highly up-regulated after GPR40 agonists treatment in the hORS cells, and also increased the proliferation and migration. Furthermore, GPR40 agonists promoted hair growth by inducing angiogenesis via ANGPTL4 in the animal experiment. GPR40 agonists activated MAPK and peroxisome proliferator-activated receptors (PPARγ) pathway in hORS cells, while the inhibition of MAPK pathway attenuated ANGPTL4 expression. Finally, GPR40 agonists increased hair growth via autocrine effects in the ORS cells, and induced angiogenesis through paracrine effects by upregulating ANGPTL4 via p38 and PPARγ pathways. As a result, GPR40 agonists have potential as a therapeutic drug for hair loss treatment.
Topics: Mice; Animals; PPAR gamma; Organ Culture Techniques; Hair
PubMed: 37002580
DOI: 10.1016/j.biopha.2023.114509 -
BMC Veterinary Research Mar 2023Feline leukemia virus (FeLV) is a retrovirus with global impact on the health of domestic cats and is usually examined by serology. In our daily clinical practice, we...
BACKGROUND
Feline leukemia virus (FeLV) is a retrovirus with global impact on the health of domestic cats and is usually examined by serology. In our daily clinical practice, we noticed that cats infected with FeLV often possess wavy whiskers (sinus hairs on the face). To investigate the relationship between wavy whiskers (WW) and FeLV infection, the association between the presence or absence of wavy changes in whiskers and serological FeLV infection was examined in a total of 358 cats including 56 cats possessing WW, using the chi-square test. The results of blood tests from 223 cases were subjected to multivariate analysis (logistic analysis). Isolated whiskers were observed under light microscopy, and upper lip tissues (proboscis) were subjected to histopathological and immunohistochemical analyses.
RESULTS
The prevalence of WW was significantly correlated with FeLV antigen positivity in the blood. Of 56 cases with WW, 50 (89.3%) were serologically positive for FeLV. The significant association between WW and serological FeLV positivity was also confirmed by multivariate analysis. In WW, narrowing, degeneration, and tearing of the hair medulla were observed. Mild infiltration of mononuclear cells in the tissues, but no degeneration or necrosis, was found. By immunohistochemistry, FeLV antigens (p27, gp70 and p15E) were observed in various epithelial cells including the sinus hair follicular epithelium of the whisker.
CONCLUSIONS
The data suggest that the wavy changes in whiskers, a unique and distinctive external sign on a cat's face, were associated with FeLV infection.
Topics: Cats; Animals; Leukemia Virus, Feline; Vibrissae; Epithelial Cells; Epithelium; Hair
PubMed: 36871053
DOI: 10.1186/s12917-023-03610-7