The past,present,and future of in vivo-implant-able recording microelectrodes:the neural interfaces / 中国药理学与毒理学杂志

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.

Confusion and countermeasures of the non-conditioned anxiety test in rodent laboratory animals / 中华行为医学与脑科学杂志

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.

Dynamic phenotype of lung type Ⅱ alveolar epithelial cells in radiation-induced lung injury and its role in the formation of fibrosis / 中华放射医学与防护杂志

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.

Altered Neuronal Activity in the Central Nucleus of the Amygdala Induced by Restraint Water-Immersion Stress in Rats / 神经科学通报·英文版

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.

Pedigree analysis of DYNC1H1 p. P776L mutation in a family with spinal muscular atrophy / 中华神经科杂志

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.

The influence of restraint water-immersion stress on firing activities of pyramidal neurons in the medial prefrontal cortex in rats / 中华行为医学与脑科学杂志

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.