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1.
Article in Chinese | WPRIM | ID: wpr-936375

ABSTRACT

OBJECTIVE@#To explore whether the characteristic responses to sound stimulations of the auditory neurons in the striatum is regulated in different behavioral states.@*METHODS@#The auditory neurons in the striatum of awake C57BL/6J mice were selected for this study. We recorded the auditory response of the striatum to noises over a long period of time by building a synchronous in vivo electrophysiological and locomotion recording system and using glass microelectrode attachment recording. By analyzing the running speed of the mice, the behavioral states of the mice were divided into the quiet state and the active state, and the spontaneous activity and evoked responses of the auditory neurons in the striatum were analyzed in these two states.@*RESULTS@#Compared with those recorded in the quiet state, the spontaneous activity of the auditory neurons in the striatum of the mice increased significantly (37.06±12.02 vs 18.51±10.91, P < 0.001) while the auditory response of the neurons decreased significantly (noise intensity=60 dB, 3.45±2.99 vs 3.04±2.76, P < 0.001) in the active state.@*CONCLUSION@#Locomotion has a significant inhibitory effect on the auditory response of the striatum, which may importantly contribute to the decline of sound information recognition ability in the active state.


Subject(s)
Acoustic Stimulation , Animals , Auditory Cortex/physiology , Evoked Potentials, Auditory , Locomotion/physiology , Mice , Mice, Inbred C57BL , Neurons
2.
Article in Chinese | WPRIM | ID: wpr-936287

ABSTRACT

OBJECTIVE@#To clarify the functional effects of differential expression of ring finger and tryptophan-aspartic acid 2 (RFWD2) on dendritic development and formation of dendritic spines in cerebral cortex neurons of mice.@*METHODS@#Immunofluorescent staining was used to identify the location and global expression profile of RFWD2 in mouse brain and determine the co-localization of RFWD2 with the synaptic proteins in the cortical neurons. We also examined the effects of RFWD2 over-expression (RFWD2-Myc) and RFWD2 knockdown (RFWD2-shRNA) on dendritic development, dendritic spine formation and synaptic function in cultured cortical neurons.@*RESULTS@#RFWD2 is highly expressed in the cerebral cortex and hippocampus of mice, and its expression level was positively correlated with the development of cerebral cortex neurons and dendrites. RFWD2 expression was detected on the presynaptic membrane and postsynaptic membrane of the neurons, and its expression levels were positively correlated with the length, number of branches and complexity of the dendrites. In cultured cortical neurons, RFWD2 overexpression significantly lowered the expressions of the synaptic proteins synaptophysin (P < 0.01) and postsynapic density protein 95 (P < 0.01), while RFWD2 knockdown significantly increased their expressions (both P < 0.05). Compared with the control and RFWD2-overexpressing cells, the neurons with RFWD2 knockdown showed significantly reduced number of dendritic spines (both P < 0.05).@*CONCLUSION@#RFWD2 can regulate the expression of the synaptic proteins, the development of the dendrites, the formation of the dendritic spines and synaptic function in mouse cerebral cortex neurons through ubiquitination of Pea3 family members and c-Jun, which may serve as potential treatment targets for neurological diseases.


Subject(s)
Animals , Aspartic Acid/metabolism , Cerebral Cortex , Dendritic Spines/metabolism , Mice , Neurons/metabolism , Synapses , Tryptophan/metabolism
3.
Article in Chinese | WPRIM | ID: wpr-936136

ABSTRACT

OBJECTIVE@#To investigate the effects of CACNA1H gene knockout (KO) on autistic-like behaviors and the morphology of hippocampal neurons in mice.@*METHODS@#In the study, 25 CACNA1H KO mice of 3-4 weeks old and C57BL/6 background were recruited as the experimental group, and 26 wild type (WT) mice of the same age and background were recruited as the control group. Three-chamber test and open field test were used to observe the social interaction, anxiety, and repetitive behaviors in mice. After that, their brain weight and size were measured, and the number of hippocampal neurons were observed by Nissl staining. Furthermore, the CACNA1H heterozygote mice were interbred with Thy1-GFP-O mice to generate CACNA1H-/--Thy1+(KO-GFP) and CACNA1H+/+-Thy1+ (WT-GFP) mice. The density and maturity of dendritic spines of hippocampal neurons were observed.@*RESULTS@#In the sociability test session of the three-chamber test, the KO mice spent more time in the chamber of the stranger mice than in the object one (F1, 14=95.086, P < 0.05; Post-Hoc: P < 0.05), without any significant difference for the explored preference index between the two groups (t=1.044, P>0.05). However, in the social novelty recognition test session, no difference was observed between the time of the KO mice spend in the chamber of new stranger mice and the stranger one (F1, 14=18.062, P < 0.05; Post-Hoc: P>0.05), and the explored preference index of the KO mice was less than that of the control group (t=2.390, P < 0.05). In the open field test, the KO mice spent less time in the center of the open field apparatus than the control group (t=2.503, P < 0.05), but the self-grooming time was significantly increased compared with the control group (t=-2.299, P < 0.05). Morphological results showed that the brain weight/body weight ratio (t=0.356, P>0.05) and brain size (t=-0.660, P>0.05) of the KO mice were not significantly different from those of the control group, but the number of neurons were significantly reduced in hippocampal dentate gyrus compared with the control group (t=2.323, P < 0.05). Moreover, the density of dendritic spine of dentate gyrus neurons in the KO-GFP mice was significantly increased compared with the control group (t=-2.374, P < 0.05), without any significant difference in spine maturity (t=-1.935, P>0.05).@*CONCLUSION@#CACNA1H KO mice represent autistic-like behavior, which may be related to the decrease in the number of neurons and the increase in the density of dendritic spine in the dentate gyrus.


Subject(s)
Animals , Autistic Disorder/genetics , Calcium Channels, T-Type/genetics , Gene Knockout Techniques , Hippocampus , Mice , Mice, Inbred C57BL , Mice, Knockout , Neurons
4.
Protein & Cell ; (12): 6-25, 2022.
Article in English | WPRIM | ID: wpr-929158

ABSTRACT

The serine/threonine p21-activated kinases (PAKs), as main effectors of the Rho GTPases Cdc42 and Rac, represent a group of important molecular switches linking the complex cytoskeletal networks to broad neural activity. PAKs show wide expression in the brain, but they differ in specific cell types, brain regions, and developmental stages. PAKs play an essential and differential role in controlling neural cytoskeletal remodeling and are related to the development and fate of neurons as well as the structural and functional plasticity of dendritic spines. PAK-mediated actin signaling and interacting functional networks represent a common pathway frequently affected in multiple neurodevelopmental and neurodegenerative disorders. Considering specific small-molecule agonists and inhibitors for PAKs have been developed in cancer treatment, comprehensive knowledge about the role of PAKs in neural cytoskeletal remodeling will promote our understanding of the complex mechanisms underlying neurological diseases, which may also represent potential therapeutic targets of these diseases.


Subject(s)
Animals , Cytoskeleton/genetics , Humans , Nervous System Diseases/genetics , Neurons/enzymology , Signal Transduction , p21-Activated Kinases/metabolism
5.
Neuroscience Bulletin ; (6): 440-452, 2022.
Article in English | WPRIM | ID: wpr-929115

ABSTRACT

Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. The processing of pain involves complicated modulation at the levels of the periphery, spinal cord, and brain. The pathogenesis of chronic pain is still not fully understood, which makes the clinical treatment challenging. Optogenetics, which combines optical and genetic technologies, can precisely intervene in the activity of specific groups of neurons and elements of the related circuits. Taking advantage of optogenetics, researchers have achieved a body of new findings that shed light on the cellular and circuit mechanisms of pain transmission, pain modulation, and chronic pain both in the periphery and the central nervous system. In this review, we summarize recent findings in pain research using optogenetic approaches and discuss their significance in understanding the pathogenesis of chronic pain.


Subject(s)
Brain , Chronic Pain , Humans , Neurons , Optogenetics , Spinal Cord
6.
Neuroscience Bulletin ; (6): 459-473, 2022.
Article in English | WPRIM | ID: wpr-929103

ABSTRACT

The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCNVm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCNVm neurons' function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.


Subject(s)
Animals , Blinking , Cerebellar Nuclei/physiology , Cerebellum , Mice , Neurons/physiology , Thalamus
7.
Neuroscience Bulletin ; (6): 249-262, 2022.
Article in English | WPRIM | ID: wpr-929098

ABSTRACT

The radial migration of cortical pyramidal neurons (PNs) during corticogenesis is necessary for establishing a multilayered cerebral cortex. Neuronal migration defects are considered a critical etiology of neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia, epilepsy, and intellectual disability (ID). TRIO is a high-risk candidate gene for ASDs and ID. However, its role in embryonic radial migration and the etiology of ASDs and ID are not fully understood. In this study, we found that the in vivo conditional knockout or in utero knockout of Trio in excitatory precursors in the neocortex caused aberrant polarity and halted the migration of late-born PNs. Further investigation of the underlying mechanism revealed that the interaction of the Trio N-terminal SH3 domain with Myosin X mediated the adherence of migrating neurons to radial glial fibers through regulating the membrane location of neuronal cadherin (N-cadherin). Also, independent or synergistic overexpression of RAC1 and RHOA showed different phenotypic recoveries of the abnormal neuronal migration by affecting the morphological transition and/or the glial fiber-dependent locomotion. Taken together, our findings clarify a novel mechanism of Trio in regulating N-cadherin cell surface expression via the interaction of Myosin X with its N-terminal SH3 domain. These results suggest the vital roles of the guanine nucleotide exchange factor 1 (GEF1) and GEF2 domains in regulating radial migration by activating their Rho GTPase effectors in both distinct and cooperative manners, which might be associated with the abnormal phenotypes in neurodevelopmental disorders.


Subject(s)
Autism Spectrum Disorder/metabolism , Cell Movement/genetics , Humans , Interneurons/metabolism , Neurodevelopmental Disorders/genetics , Neurons/metabolism , Rho Guanine Nucleotide Exchange Factors/genetics
8.
Neuroscience Bulletin ; (6): 489-504, 2022.
Article in English | WPRIM | ID: wpr-929090

ABSTRACT

Studies have shown that spatial attention remarkably affects the trial-to-trial response variability shared between neurons. Difficulty in the attentional task adjusts how much concentration we maintain on what is currently important and what is filtered as irrelevant sensory information. However, how task difficulty mediates the interactions between neurons with separated receptive fields (RFs) that are attended to or attended away is still not clear. We examined spike count correlations between single-unit activities recorded simultaneously in the primary visual cortex (V1) while monkeys performed a spatial attention task with two levels of difficulty. Moreover, the RFs of the two neurons recorded were non-overlapping to allow us to study fluctuations in the correlated responses between competing visual inputs when the focus of attention was allocated to the RF of one neuron. While increasing difficulty in the spatial attention task, spike count correlations were either decreased to become negative between neuronal pairs, implying competition among them, with one neuron (or none) exhibiting attentional enhancement of firing rate, or increased to become positive, suggesting inter-neuronal cooperation, with one of the pair showing attentional suppression of spiking responses. Besides, the modulation of spike count correlations by task difficulty was independent of the attended locations. These findings provide evidence that task difficulty affects the functional interactions between different neuronal pools in V1 when selective attention resolves the spatial competition.


Subject(s)
Animals , Attention/physiology , Macaca mulatta , Neurons/physiology , Photic Stimulation , Primary Visual Cortex , Visual Cortex/physiology
9.
Neuroscience Bulletin ; (6): 474-488, 2022.
Article in English | WPRIM | ID: wpr-929086

ABSTRACT

Astrocytes are increasingly recognized to play an active role in learning and memory, but whether neural inputs can trigger event-specific astrocytic Ca2+ dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca2+ dynamics in animals performing tasks. Here, using fiber photometry, we showed that population astrocytic Ca2+ dynamics in the hippocampus were gated by sensory inputs (centered at the turning point of the T-maze) and modified by the reward delivery during the encoding and retrieval phases. Notably, there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca2+ dynamics with a 3-s phase difference. Furthermore, there was a robust synchronization of astrocytic Ca2+ at the population level among the hippocampus, medial prefrontal cortex, and striatum. The inter-locked, bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.


Subject(s)
Animals , Astrocytes , Hippocampus/physiology , Humans , Memory, Short-Term/physiology , Mice , Neurons/physiology , Population Dynamics
10.
Neuroscience Bulletin ; (6): 81-94, 2022.
Article in English | WPRIM | ID: wpr-929082

ABSTRACT

Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality; however, the underlying cellular and molecular mechanisms remain largely unknown. Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited. Here, we describe a new mouse model of congenital hydrocephalus through knockout of β-catenin in Nkx2.1-expressing regional neural progenitors. Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood. Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis after β-catenin knockout. Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages. Thus, knockout of β-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.


Subject(s)
Animals , Disease Models, Animal , Hydrocephalus/genetics , Mice , Mice, Knockout , Neurons , beta Catenin/genetics
11.
Neuroscience Bulletin ; (6): 149-165, 2022.
Article in English | WPRIM | ID: wpr-929077

ABSTRACT

Leptin, an adipocyte-derived peptide hormone, has been shown to facilitate breathing. However, the central sites and circuit mechanisms underlying the respiratory effects of leptin remain incompletely understood. The present study aimed to address whether neurons expressing leptin receptor b (LepRb) in the nucleus tractus solitarii (NTS) contribute to respiratory control. Both chemogenetic and optogenetic stimulation of LepRb-expressing NTS (NTSLepRb) neurons notably activated breathing. Moreover, stimulation of NTSLepRb neurons projecting to the lateral parabrachial nucleus (LPBN) not only remarkably increased basal ventilation to a level similar to that of the stimulation of all NTSLepRb neurons, but also activated LPBN neurons projecting to the preBötzinger complex (preBötC). By contrast, ablation of NTSLepRb neurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTSLepRb neuron stimulation. In brainstem slices, bath application of leptin rapidly depolarized the membrane potential, increased the spontaneous firing rate, and accelerated the Ca2+ transients in most NTSLepRb neurons. Therefore, leptin potentiates breathing in the NTS most likely via an NTS-LPBN-preBötC circuit.


Subject(s)
Leptin/pharmacology , Membrane Potentials , Neurons/metabolism , Solitary Nucleus/metabolism
12.
Chinese Journal of Stomatology ; (12): 375-383, 2022.
Article in Chinese | WPRIM | ID: wpr-935870

ABSTRACT

Objectives: To study the effects of Porphyromonas gingivalis (Pg) injected through tail vein on the molecular expression levels of biomarkers of neural stem cells (NSC) and neurons in the hippocampus of wild-type adult rats, and the effects on hippocampal neurogenesis. Methods: Eighteen male Sprague-Dawley (SD) rats were randomly divided into 3 groups based on the table of random numbers (n=6 in each group). In low-intensity group and high-intensity group, rats were injected intravenously through tail vein with 200 μl Pg ATCC33277 [1.0×103 and 1.0×108 colony forming unit (CFU), respectively] 3 times per week for 8 weeks. In the sham group, 200 μl of phosphate buffer saline (PBS) was given instead. Behavioral tests: the navigation and the exploration tests using Morris water maze (MWM) were applied to evaluate learning and memory ability of rats. Immunohistochemistry was performed to detect cells positively expressing nestin, doublecortin (DCX) and neuronal nuclei (NeuN) in the subgranular zone (SGZ) of rats in each group. Western blotting was used to evaluate the expression levels of nestin, DCX and NeuN in rat hippocampus. Results: Learning and memory abilities: on day 5 of navigation test, the lagency time was 22.83 (16.00, 38.34) s in the high-intensity group, significantly longer than the sham group [5.59 (5.41, 6.17) s] (t=-11.17, P<0.001). There were no significant differences between the low-intensity group [9.85 (8.75, 21.01) s] and the sham group (t=-6.83, P=0.080). Results in the exploration test showed that, in the high-intensity group, the number of fime crossing over the previous platform area within 60 s was 1.50 (1.00, 2.00), significantly less than the sham group [4.00 (2.75, 4.00)] (t=9.75, P=0.003); no significant differences between the low-intensity group [2.50 (2.00, 3.00)] and the sham one (t=4.50, P=0.382). Immunohistochemistry showed that the nestin+ cell density in the low-intensity group [(35.36±4.32) cell/mm2] and high-intensity group [(26.51±5.89) cell/mm2] were significantly lower than the sham group [(59.58±14.15) cell/mm2] (t=24.21, P=0.018; t=33.07, P=0.005); as for the mean absorbance of DCX+ cells, the low-intensity group (0.007±0.002) and the high-intensity group (0.006±0.002) were significantly lower than the sham group (0.011±0.001) (t=0.004, P=0.018; t=0.006, P=0.005); compared with the sham group [(1.13±0.14)×103 cell/mm2], the density of NeuN+ neurons in the high-intensity group [(0.75±0.08)×103 cell/mm2] was significantly reduced (t=0.38, P=0.017), and was not significantly changed in the low-intensity group [(0.88±0.19)×103 cell/mm2] (t=0.25, P=0.075). Western blotting results showed that, compared with the sham group, the expression levels of nestin, DCX, and NeuN were significantly reduced in the high-intensity group (t=0.74, P<0.001; t=0.18, P=0.014; t=0.35, P=0.008), but were not statistically changed in the low-intensity group (t=0.18, P=0.108; t=0.08, P=0.172; t=0.19, P=0.077). Conclusions: Pg injected through tail vein may reduce learning and memory abilities of wild-type rats, and may reduce the number of nestin, DCX, and NeuN-positive cells, and the protein expression levels of the above molecules in the hippocampus.


Subject(s)
Animals , Biomarkers/metabolism , Hippocampus/metabolism , Male , Nestin/metabolism , Neural Stem Cells/metabolism , Neurons/metabolism , Porphyromonas gingivalis/metabolism , Rats , Rats, Sprague-Dawley , Tail/metabolism
13.
Article in Chinese | WPRIM | ID: wpr-935769

ABSTRACT

Objective: To investigate the effect and underlying mechanism of paeoniflorin on hippocampal neuron apoptosis induced by lead acetate. Methods: In September 2020, primary hippocampal neuronal cells were isolated and cultured from fetal rats, and identified using cellular immunofluorescent. MTT assay was used to measure the cell viability to determine the concentration and time of lead acetate-induced hippocampal neuron apoptosis. MTT was also used to evaluate the effect of paeoniflorin concentration on the apoptosis of hippocampal neurons induced by lead acetate. According to the results, different concentrations of paeoniflorin were selected to intervene hippocampal neuron cells, after 24 h, lead acetate was added to the cells, meanwhile, blank and model groups were set up, the content of reactive oxygen species (ROS) , superoxide dismutase (SOD) , lactate dehydrogenase (LDH) , malondialdehyde (MDA) and Caspase-3 were measured. Extracellular signal regulated kinase (ERK) , phosphorylated ERK (p-ERK) , p38 mitogen -activated protein kinases (p38MAPK) , phosphorylated p38MAPK (p-p38MAPK) , c-Jun N-terminal kinase (JNK) and phosphorylated JNK (p-JNK) protein expression in hippocampal neuronal cells were determined by Western blotting. Results: The isolated and cultured hippocampal neurons were identified by immunofluorescence chemical staining and then treated with lead acetate, MTT results showed that lead acetate had the best toxicity effect when treated for 24 h at a concentration of 25 μmol/L. Paeoniflorin showed no cytotoxic effect on hippocampal neuronal cells when the concentrations below 80 μmol/L. Compared with the model group, the activity of hippocampal neuronal cells was significantly increased after treating with 20, 40 or 80 μmol/L paeoniflorin (P<0.05) . Compared with the blank group, the ROS activity, LDH release level, MDA content and caspase-3 content were significantly increased (P<0.01) , and the SOD activity was significantly decreased (P< 0.01) in the hippocampal neuronal cells of the model group. Compared with the model group, the ROS activity, LDH release level, MDA content and caspase-3 content were obviously decreased (P<0.05) , SOD activity was significantly increased (P <0.01) after hippocampal neuronal cells were treated with 40 or 80 μmol/L paeoniflorin. Relative to the model group, the ratio of p-ERK/ERK were significantly up-regulated (P<0.01) , while the ratios of p-p38MAPK/p38MAPK and p-JNK/JNK were significantly down-regulated after hippocampal neuronal cells were treated with 40 or 80 μmol/L paeoniflorin (P<0.05) . Conclusion: Paeoniflorin may down-regulate the expression of p-p38MAPK and p-JNK protein, up-regulate the expression of p-ERK protein, and inhibit the apoptosis of hippocampal neurons induced by lead acetate through the MAPK signaling pathway.


Subject(s)
Acetates/pharmacology , Animals , Apoptosis , Caspase 3/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Glucosides , Hippocampus/metabolism , JNK Mitogen-Activated Protein Kinases/pharmacology , Lead , Monoterpenes , Neurons/metabolism , Rats , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
14.
Protein & Cell ; (12): 203-219, 2022.
Article in English | WPRIM | ID: wpr-929177

ABSTRACT

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABAA receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.


Subject(s)
Animals , Disease Models, Animal , Fragile X Mental Retardation Protein/metabolism , Fragile X Syndrome/metabolism , Humans , Mice , Mice, Knockout , Neurons/metabolism
15.
Neuroscience Bulletin ; (6): 841-856, 2022.
Article in English | WPRIM | ID: wpr-939846

ABSTRACT

Epilepsy is a common and severe brain disease affecting >65 million people worldwide. Recent studies have shown that kinesin superfamily motor protein 17 (KIF17) is expressed in neurons and is involved in regulating the dendrite-targeted transport of N-methyl-D-aspartate receptor subtype 2B (NR2B). However, the effect of KIF17 on epileptic seizures remains to be explored. We found that KIF17 was mainly expressed in neurons and that its expression was increased in epileptic brain tissue. In the kainic acid (KA)-induced epilepsy mouse model, KIF17 overexpression increased the severity of epileptic activity, whereas KIF17 knockdown had the opposite effect. In electrophysiological tests, KIF17 regulated excitatory synaptic transmission, potentially due to KIF17-mediated NR2B membrane expression. In addition, this report provides the first demonstration that KIF17 is modified by SUMOylation (SUMO, small ubiquitin-like modifier), which plays a vital role in the stabilization and maintenance of KIF17 in epilepsy.


Subject(s)
Animals , Epilepsy/metabolism , Kinesins/metabolism , Mice , Neurons/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Seizures/metabolism
16.
Neuroscience Bulletin ; (6): 796-808, 2022.
Article in English | WPRIM | ID: wpr-939839

ABSTRACT

In contrast to traditional representational perspectives in which the motor cortex is involved in motor control via neuronal preference for kinetics and kinematics, a dynamical system perspective emerging in the last decade views the motor cortex as a dynamical machine that generates motor commands by autonomous temporal evolution. In this review, we first look back at the history of the representational and dynamical perspectives and discuss their explanatory power and controversy from both empirical and computational points of view. Here, we aim to reconcile the above perspectives, and evaluate their theoretical impact, future direction, and potential applications in brain-machine interfaces.


Subject(s)
Biomechanical Phenomena , Brain-Computer Interfaces , Motor Cortex/physiology , Neurons/physiology
17.
Neuroscience Bulletin ; (6): 741-752, 2022.
Article in English | WPRIM | ID: wpr-939833

ABSTRACT

Environmental threats often trigger innate defensive responses in mammals. However, the gradual development of functional properties of these responses during the postnatal development stage remains unclear. Here, we report that looming stimulation in mice evoked flight behavior commencing at P14-16 and had fully developed by P20-24. The visual-evoked innate defensive response was not significantly altered by sensory deprivation at an early postnatal stage. Furthermore, the percentages of wide-field and horizontal cells in the superior colliculus were notably elevated at P20-24. Our findings define a developmental time window for the formation of the visual innate defense response during the early postnatal period and provide important insight into the underlying mechanism.


Subject(s)
Animals , Evoked Potentials, Visual , Fear/physiology , Mammals , Mice , Mice, Inbred C57BL , Neurons/physiology , Superior Colliculi/physiology
18.
Article in English | WPRIM | ID: wpr-939803

ABSTRACT

OBJECTIVES@#Neuropathic pain (NP) is a chronic pain caused by somatosensory neuropathy or disease, and genistein (Gen) might be a potential drug for the treatment of NP. Therefore, this study aims to investigate the effect of Gen on lipopolysaccharide (LPS)-induced inflammatory injury of dorsal root ganglion neuron (DRGn) in rats and the possible molecular mechanism.@*METHODS@#The DRGn of 1-day-old juvenile rats were taken for isolation and culture. The DRGn in logarithmic growth phase were divided into a control group, a LPS group, a tubastatin hydrochloride (TSA)+LPS group, a Gen1+LPS group, a Gen2+LPS group, a Gen2+LPS+TSA group, a Gen2+pcDNA-histone deacetylase 6 (HDAC6)+LPS group, and a Gen2+pcDNA3.1+LPS group. The LPS group was treated with 1 μg/mL LPS for 24 h; the TSA+LPS group, the Gen1+LPS group, the Gen2+LPS group were treated with 5 μmol/L TSA, 5 μmol/L Gen, 10 μmol/L Gen respectively for 0.5 h, and then added 1 μg/mL LPS for 24 h; the Gen2+TSA+LPS group was treated with 10 μmol/L Gen and 5 μmol/L TSA for 0.5 h and then added 1 μg/mL LPS for 24 h; the Gen2+pcDNA-HDAC6+LPS group and the Gen2+pcDNA3.1+LPS group received 100 nmol/L pcDNA-HDAC6 and pcDNA3.1 plasmids respectively, and 24 h after transfection, 10 μmol/L Gen was pretreated for 0.5 h, and then added 1 μg/mL LPS for 24 h. Real-time RT-PCR was used to detect the HDAC6 mRNA expression in DRGn; CCK-8 method was used to detect cell viability of DRGn; flow cytometry was used to detect cell apoptosis of DRGn; ELISA was used to detect the levels of IL-1β, IL-6, and TNF-α in DRGn culture supernatant; Western blotting was used to detect the protein expression of HDAC6, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and NF-κB p65 in DRGn.@*RESULTS@#Compared with the control group, the expression levels of HDAC6 mRNA and protein, the expression levels of TLR4 and MyD88 protein in DRGn of LPS group rats were significantly up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was significantly increased, and the activity of DRGn was significantly decreased, the apoptosis rate was significantly increased, and the levels of IL-1β, IL-6 and TNF-α in the DRGn culture supernatant were significantly increased (all P<0.05). Compared with the LPS group, the expression levels of HDAC6 mRNA and protein, TLR4 and MyD88 protein expression levels in DRGn of the TSA+LPS group, the Gen1+LPS group, the Gen2+LPS group and the Gen2+TSA+LPS group were significantly down-regulated, the ratio of p-NF-κB p65/NF-κB p65 was significantly decreased, the activity of DRGn was significantly increased, the apoptosis rate was significantly decreased, and the levels of IL-1β, IL-6 and TNF-α in the DRGn culture supernatant were significantly decreased (all P<0.05), and the above changes were most obvious in the Gen2+TSA+LPS group. Compared with the Gen2+LPS group, the expression levels of HDAC6 mRNA and protein, TLR4 and MyD88 protein expression levels in DRGn of the Gen2+pcDNA-HDAC6+LPS group were significantly up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was significantly increased, the activity of DRGn was significantly decreased, and the apoptosis rate was significantly increased, and the levels of IL-1β, IL-6 and TNF-α in the DRGn culture supernatant were significantly increased (all P<0.05).@*CONCLUSIONS@#Gen can alleviate LPS-induced DRGn inflammatory injury in rats, which might be related to down-regulating the expression of HDAC6 and further inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway.


Subject(s)
Animals , Ganglia, Spinal , Genistein/pharmacology , Histone Deacetylase 6/metabolism , Interleukin-6/metabolism , Lipopolysaccharides , Myeloid Differentiation Factor 88 , NF-kappa B/metabolism , Neurons/metabolism , RNA, Messenger , Rats , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolism
19.
Article in Chinese | WPRIM | ID: wpr-927903

ABSTRACT

Objective: To compare the difference between the built-in and external reference electrode of microwire electrode array in the process of recording rat brain neuron firings, optimizing the production and embedding of the microwire electrode array, and providing a more affordable and excellent media tool for multi-channel electrophysiological real-time recording system. Methods: A 16 channel microwire electrode array was made by using nickel chromium alloy wires, circuit board, electrode pin and ground wires (silver wires). The reference electrode of the microwire electrode array was built-in (the reference electrode and electrode array were arranged in parallel) or external (the reference electrode and ground wire were welded at both ends of one side of the electrode), and the difference between the two electrodes was observed and compared in recording neuronal discharges in ACC brain area of rats. Experimental rats were divided into built-in group and external group, n=8-9. The test indicators included signal-to-noise ratio (n=8), discharge amplitude (n=380) and discharge frequency (n=54). Results: The microwire electrode array with both built-in and external reference electrodes successfully recorded the electrical signals of neurons in the ACC brain region of rats. Compared with the external group, the electrical signals of neurons in built-in group had the advantages of a higher signal-to-noise ratio (P<0.05), a smaller amplitude of background signals and less noise interference, and a larger discharge amplitude(P<0.05); there was no significant difference in spike discharge frequency recorded by these two types of electrodes (P>0.05). Conclusion: When recording the electrical activity of neurons in the ACC brain region of rats, the microwire electrode array with built-in reference electrode recorded electrical signals with higher signal-to-noise ratio and larger discharge amplitude, providing a more reliable tool for multi-channel electrophysiology technology.


Subject(s)
Action Potentials/physiology , Animals , Brain , Electrophysiological Phenomena , Microelectrodes , Neurons , Rats
20.
Acta Physiologica Sinica ; (6): 135-144, 2022.
Article in Chinese | WPRIM | ID: wpr-927589

ABSTRACT

Vestibular compensation is an important model for developing the prevention and intervention strategies of vestibular disorders, and investigating the plasticity of the adult central nervous system induced by peripheral injury. Medial vestibular nucleus (MVN) in brainstem is critical center for vestibular compensation. Its neuronal excitability and sensitivity have been implicated in normal function of vestibular system. Previous studies mainly focused on the changes in neuronal excitability of the MVN in lesional side of the rat model of vestibular compensation following the unilateral labyrinthectomy (UL). However, the plasticity of sensitivity of bilateral MVN neurons dynamically responding to input stimuli is still largely unknown. In the present study, by using qPCR, whole-cell patch clamp recording in acute brain slices and behavioral techniques, we observed that 6 h after UL, rats showed a significant deficit in spontaneous locomotion, and a decrease in excitability of type B neurons in the ipsilesional rather than contralesional MVN. By contrast, type B neurons in the contralesional rather than ipsilesional MVN exhibited an increase in response sensitivity to the ramp and step input current stimuli. One week after UL, both the neuronal excitability of the ipsilesional MVN and the neuronal sensitivity of the contralesional MVN recovered to the baseline, accompanied by a compensation of spontaneous locomotion. In addition, the data showed that the small conductance Ca2+-activated K+ (SK) channel involved in the regulation of type B MVN neuronal sensitivity, showed a selective decrease in expression in the contralesional MVN 6 h after UL, and returned to normal level 1 week later. Pharmacological blockage of SK channel in contralateral MVN to inhibit the UL-induced functional plasticity of SK channel significantly delayed the compensation of vestibular motor dysfunction. These results suggest that the changes in plasticity of the ipsilesional MVN neuronal excitability, together with changes in the contralesional MVN neuronal sensitivity, may both contribute to the development of vestibular symptoms as well as vestibular compensation, and SK channel may be an essential ionic mechanism responsible for the dynamic changes of MVN neuronal sensitivity during vestibular compensation.


Subject(s)
Animals , Locomotion , Neurons/physiology , Patch-Clamp Techniques , Rats , Vestibular Nuclei/metabolism , Vestibule, Labyrinth
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