Objective To explore the effects of restraint water-immersion stress (RWIS) on the firing activities of pyramidal neurons in the medial prefrontal cortex (MPFC) of rats.Methods Multi-channel in vivo recording techniques were used to record firing activities of pyramidal neurons before and during 4-h RWIS in rats.Firing rates,inter-spike intervals and burst firing rates were taken as indices to study the influence of RWIS on neuronal firing activities.Results Twenty-five pyramidal neurons of 12 rats were recorded.The opposite patterns of firing activities were observed in two different classes of neurons,type A and type B neurons which account for 72％ and 28％,respectively.In type A neurons,inhibited firing activities were in direct proportion to the stress-exposure.Mean firing rates and mean burst firing rates were significantly reduced to (0.81 ± 0.11) Hz and (1.012 ± 0.50) counts/min after 4h constant RWIS compared with those before RWIS,(3.57 ± 0.63) Hz and (10.29 ± 3.04) counts/min.However,in type B neurons,firing activities were enhanced.After 2h constant RWIS,mean firing rates and mean burst firing rates were increased from (1.77±0.45) Hz and (2.01±0.73) counts/min to (2.67±0.74)Hz and (9.04±2.42) counts/min,respectively.Moreover,the percentage of spikes in bursts was significantly increased and mean inter-spike intervals were remarkably shortened.Interestingly,the effect of RWIS on type B neurons lasted for shorter time compared with its effect on type A neurons.Conclusion RWIS differentially affects the firing activity of pyramidal neuron in the MPFC,i.e.,inhibiting the firing activity of type A neurons,but enhancing the firing activity of type B neurons.

Objective To analyze the clinical and electrophysiological features in a family with spinal muscular atrophy (SMA), and assess the probable causative gene mutations for the family. Methods To identify the nosogenesis of the proband with weakness and atrophy in the double lower proximal limbs, clinical data of his 12 family members were collected, and the proband and his mother were selected for clinical examinations, including laboratory tests, electromyogram (EMG), F-wave, H-reflex, X-ray of the spine and double lower limbs, brain and spinal cord magnetic resonance imaging, etc. Moreover, human whole exome sequencing was performed on blood sample from the proband, then its deleterious effects were assessed according to the Standards and guidelines for the interpretation of sequence variants, a joint consensus recommendation of the American College of Medical Genomics (ACMG) and the Association for Molecular Pathology (AMP). Subsequently, the strong pathogenic mutation was validated by Sanger sequencing. Results Familial investigation showed seven of 12 family members presented with weakness in the double lower proximal limbs. Among them, three had the main manifestation of atrophy in the double lower proximal limbs, one had high arched foot as the main presentation, and the others had weakness in the double lower proximal limbs. EMG studies showed the abnormal results in the anterior horn of the spinal cord. The strong pathogenic mutation in DYNC1H1 gene (exon8, c.2327C＞T, p.P776L) was identified from the proband according to ACMG and AMP guidelines. Sanger sequencing revealed six patients had this variant and it was passed mainly from his maternal grandmother. Conclusions A pathogenic mutation of the DYNC1H1 p.P776L in six Chinese pedigrees which cosegregated with SMA was identified. There existed individual differences in clinical presentations. This finding may have important implications for the study of SMA in Chinese patients.

Objective To study the effect of dopamine D1 receptor antagonist SCH23390 on the behavior of parkinsonian (PD) rats and on electrophysiological characteristics of the entopeduncular nucleus (EP).Methods Intracranial injection of 6-OHDA was conducted in 23 adult male Wistar rats to create PD animal models (experimental group) while the same amount of normal saline was injected in another 19 rats as a control group.(1) After intraperitoneal injection of SCH23390 at various concentrations of 0.010,0.015,0.020,0.025 and 0.030 mg/kg,the step frequency and the discontinuous moving frequency tests were carried out to determine the optimal concentration and time of intervention at 6 time points (10 main before,and 5～15,20～30,30～40,40～50 and 68～78 min after intervention) when all the rats were put on a treadmill at a speed of 8 r/min.(2) After recording electrodes were implanted into the EP in the rats,the signals of spikes in the EP in still and movement conditions were recorded simultaneously using the 16-Channel OmniPlex Neural Data Acquisition System.The spike signals collected were imported into Offiine Sorter to do cluster-sorting analysis and then into NeuroExplorer to analyze alterations in the firing pattern and firing rate of each type of neuron.(3) Frozen sections of the brain samples harvested by perfusion from the rats in the 2 groups were subjected to Nissl's staining and histological assay.Results (1) The behavioral tests showed that intraperitoneal injection of SCH23390 at 0.020 mg/kg at time points of 20～30 min and 30～40 min was optimal.The step frequency for the experimental group (24.47±1.35 step/min) was significantly decreased compared with that for the control group (30.77±2.06 step/min) (t=7.392,P=0.000).(2) After intervention by SCH23390,in movement and still conditions,the firing rate and variation coefficient of EP neurons were significantly higher in the experimental group than in the control group (P＜0.05).(3) The Nissl's staining showed a small number of lightly stained neurons were sparsely disposed in the injured cerebral substantia nigra and the histological assay found altogether 14 rats from which correct EP sites were collected.Conclusions This study demonstrated a negative regulating effect of dopamine D1 receptor antagonist SCH23390 on the behavior of PD rats,which may be exerted by changing the electrophysiological activity of EP.

Chemogenetic technology is a receptor-ligand system that regulates cell viability and function by changing receptor specificity and affinity, and it achieves precise neuronal regulation by specifically regulating neurons and neural circuits. At present, this technique is widely used in the study of neural circuits. This article briefly describes the application and progress of chemogenetic technology in the study of depression neural circuits, reviews the application of chemogenetic technology in several brain regions closely related to depression, such as ventral tegmental area, nucleus accumbens, prefrontal cortex, hippocampus and lateral habenula, and discusses the potential and challenges of chemogenetic technology as a technology for precise regulation of neural activity in future research, in order to provide reliable ideas and directions for chemogenetic technology in the study of depression neural circuits.

Neural recording electrodes enable the acquisition and collection of electrical signals from neu-rons,and these recorded neural electrical signals are an important means of understanding neuronal activity.As a major component of the brain-machine interface,neu-ral recording electrodes serve as a bridge between the nervous system and external devices.The extracted information can be used to understand the state of the brain and acts as a feedback signal to regulate external devices,thus providing important information for the clini-cal treatment of neurological diseases.Moreover,the electrodes can be used as a vehicle for drug injection to directly treat diseases.Since the time that Strumwas-ser used microwires to achieve long-term recordings of neural activity in hibernating squirrels,implantable elec-trode technology has gradually improved over three gen-erations of development,and progress has been made in improving the biocompatibility,mechanical performance(size,shape,density,etc.),and signal-to-noise ratio.Implantable neural recording electrodes can acquire sig-nals from cortical and deep neural clusters,with the advantages of high signal-to-noise ratio,information con-tent,and spatial/temporal resolution.However,there is still a need to improve the structure and performance of these electrodes;for example,their high invasiveness and lack of biocompatibility pose technical difficulties in the process of translation to the clinic.This paper reviews the basic requirements for electrodes,main recording methods and signal types,common types of implant-able neural recording electrodes,and their challenges and future development directions.With the continuous development of electrode materials,equipment,systems,and neurotechnology,it should be possible to apply neu-ral recording electrodes in clinical practice,to promote safe and efficient treatment of human diseases.

Objective:To explore the dynamic phenotype of type Ⅱ alveolar epithelial cells(AEC Ⅱ)in radiation-induced lung fibrosisand its role in the formation of fibrosis.Methods:Totally 90 C57BL/6J female mice were divided into 2 groups: irradiation group (50, thoracic irradiation with a single dose of 20 Gy X-rays), control group (40, sham irradiation). At 24 h, 4 and 12 weeks after irradiation, 5 mice were euthanized and the lungs were collected for pathological observation. The other lungtissues were collected for the isolation of primary AEC Ⅱ cells with microbeadssorting.The mRNA expressions of proSP-C, HOPX, vimentin, β-catenin and TGF-β1 in AEC II cells were detected by RT-PCR.Results:Acute pneumonitis was observed in the lungs at 24 h after irradiation and alleviated in accompany with partial alveolar septal thickening and a small amount of collagen deposition at 4 weeks after irradiation. The collagen deposition became more pronounced at 12 weeks after irradiation, together with collapsed and fused alveolar cavities, alveolar septal hyperplasia, and pulmonary fibrosis formation.The mRNAexpression levels of proSP-C and HOPX in primary AEC Ⅱ cells increased at 24 hours after irradiation and then approached to a peak value at 4 weeks after irradiation ( F=8.441, 3.586, P=0.036). The mRNA expression levels of vimentin, a biomarker of EMT, was increased significantly at 4 weeks and continued up to 12 weeks after irradiation( F=8.358, P=0.001). The mRNA expression levels of profibrotic factors β-catenin and TGF-β1 were both significant increased at 12 weeks after irradiation( F=4.62, 3.279, P=0.044). Conclusions:The phenotypeof AECⅡ cells could not only be transformed from proSP-C+ to HOPX+ /proSP-C+ , HOPX+ /proSP-C+ /vimentin+ , and vimentin+ /proSP-C, but also differentiated into mesenchymal cells with highly expressed profibrotic factors, thereby inducing EMT process, which either played a role in the repair of radiation-induced lung injury or triggered radiation-induced fibrosis.

Neurodegenerative diseases are a type of disease characterized by specific types of neuronal loss and progressive progression,mainly represented by Alzheimer's disease and Parkinson's disease.This type of disease,due to its intractable and irreversible symptoms,brings great physical and psychological burden to patients,which is seriously disturbing their normal life.In terms of treatment,there is currently no specific treatment for Alzheimer's disease in clinical practice,and first-line treatment drugs for Parkinson's disease also have great limitations.In traditional Chinese medicine,kidney governs bone,generates marrow,and connects to the brain.In clinical evidence typing,premature aging,fatigue and forgetfulness,and tremor of limbs caused by kidney deficiency and medullary reduction are considered to be the main pathologies of these diseases.Di-Huang-Yin-Zi decoction which is derived from the"General Records of Holy Universal Relief",is recorded as a good formula for nourishing kidney yin and filling kidney yang.Clinical data shows that this formula has significant therapeutic effects in treating neurodegenerative diseases caused by kidney essence deficiency.Modern research results indicate that its mechanism of action involves inhibiting inflammatory reactions,regulating mitochondrial autophagy,reversing The hypothalamic-pituitary-adrenal axis abnormalities,and neuroprotection.The main effective ingredients in this formula include loganin,echinarin,and schisandrin A.This article aims to summarize and analyze the clinical efficacy,mechanism of action,and active ingredients of Di-Huang-Yin-Zi decoction in the treatment of Alzheimer's and Parkinson's disease in recent years,in order to clarify the research status of Di-Huang-Yin-Zi decoction in the neurodegenerative disease and provide reference for further research.

Anxiety is a major mood disorder, and the high morbidity, co-morbidity and disability of anxiety disorders seriously affect people's quality of life, so the importance and urgency of research on anxiety cannot be overstated. Animal models are the main carriers for studying the mechanism of disease occurrence and development, drug efficacy evaluation and drug development.Unconditioned anxiety model is a common anxiety model.Elevated plus maze test, open field test and light-dark box test are widely accepted paradigms for the detection of unconditioned anxiety.This kind of behavioral paradigm based on environmental exposure takes advantage of the conflict between curiosity and fear of the unfamiliar environment to simulate and detect the anxiety of animals.However, the validity of these behavioral paradigms for evaluating anxiety in animals is questionable.In this paper, we discuss the concept of anxiety, the definition of anxiety behavior in the behavioral test of unconditioned anxiety, and the factors to be considered in the test of unconditioned anxiety behavior.On this basis, new solutions were proposed to the contradictions and blind spots in order to improve the test paradigm of anxiety behavior and provide a more reliable animal model for the evaluation of anxiety.This paper presents a new approach to address the contradictions and blind spots of this paradigm.

Restraint water-immersion stress (RWIS), a compound stress model, has been widely used to induce acute gastric ulceration in rats. A wealth of evidence suggests that the central nucleus of the amygdala (CEA) is a focal region for mediating the biological response to stress. Different stressors induce distinct alterations of neuronal activity in the CEA; however, few studies have reported the characteristics of CEA neuronal activity induced by RWIS. Therefore, we explored this issue using immunohistochemistry and in vivo extracellular single-unit recording. Our results showed that RWIS and restraint stress (RS) differentially changed the c-Fos expression and firing properties of neurons in the medial CEA. In addition, RWIS, but not RS, induced the activation of corticotropin-releasing hormone neurons in the CEA. These findings suggested that specific neuronal activation in the CEA is involved in the formation of RWIS-induced gastric ulcers. This study also provides a possible theoretical explanation for the different gastric dysfunctions induced by different stressors.
Action Potentials ; drug effects ; physiology ; Analysis of Variance ; Animals ; Central Amygdaloid Nucleus ; pathology ; Corticotropin-Releasing Hormone ; metabolism ; Disease Models, Animal ; Gastric Mucosa ; pathology ; Gene Expression Regulation ; physiology ; Neurons ; physiology ; Patch-Clamp Techniques ; Proto-Oncogene Proteins c-fos ; metabolism ; Rats ; Rats, Wistar ; Stress, Physiological ; physiology ; Stress, Psychological ; etiology ; physiopathology

The neural circuit is the material carrier for the realization of brain function,consisting of a complex network of different neurons.Neural circuit identification technology tracks the structure and activity of specific neural circuits,to study their adequacy and necessity for brain function,which is crucial for understanding the pathogenesis of brain diseases.As a high-tech tool in the fields of neuroscience and brain science,neural circuit identification technology has been gradually introduced into basic traditional Chinese medicine(TCM)research in recent years.This systematic review considers the principles of neural circuit identification technology and progress in its application in the field of TCM neuroscience.We note that future developments in this field should be based on the overall concept of TCM characteristics and the design of syndrome differentiation and treatment.Further research on the neural circuit mechanisms of diverse method of TCM in diseases will help to promote the deep integration of TCM and modern neuroscience.