Different coding characteristics between flight and freezing in dorsal periaqueductal gray of mice during exposure to innate threats

Background:Flight and freezing are two vital defensive behaviors that mice display to avoid natural enemies.When they are exposed to innate threats,visual cues are processed and transmitted by the visual system into the emotional nuclei and finally transmitted to the periaqueductal gray(PAG)to induce defensive behaviors.However,how the dorsal PAG(dPAG)encodes the two defensive behaviors is unclear.Methods:Multi-array electrodes were implanted in the dPAG nuclei of C57BL/6 mice.Two kinds of visual stimuli(looming and sweeping)were used to induce defensive behaviors in mice.Neural signals under different defense behaviors were recorded,and the encoding characteristics of the two behaviors were extracted and analyzed from spike firing and frequency oscillations.Finally,synchronization of neural activity during the defense process was analyzed.Results:The neural activity between flight and freezing behaviors showed different firing patterns,and the differences in the inter-spike interval distribution were mainly reflected in the 2–10 ms period.The frequency band activities under both defensive behaviors were concentrated in the theta band;the active frequency of flight was~8to 10 Hz,whereas that of freezing behavior was~6 to 8 Hz.The network connection density under both defense behaviors was significantly higher than the period before and after defensive behavior occurred,indicating that there was a high synchronization of neural activity during the defense process.Conclusions:The dPAG nuclei of mice have different coding features between flight and freezing behaviors;during strong looming stimulation,fast neuro-i nstinctive decision making is required while encountering weak sweeping stimulation,and computable planning late behavior is predicted in the early stage.The frequency band activities under both defensive behaviors were concentrated in the theta band.There was a high synchronization of neural activity during the defense process,which may be a key factor triggering different defensive behaviors.

互联网赋能如何影响政府相对贫困治理绩效?--开放式创新的中介作用

数字乡村战略实施和新冠肺炎疫情抗击,使得以互联网为基础的新一代信息技术在相对贫困治理中日益发挥着重要作用。但作为一个新兴的研究热点,互联网如何赋能相对贫困治理研究尚有待进一步深化。论文采用多元回归分析方法,构建互联网赋能、开放式创新治贫(内部协同治贫、社会协同治贫及帮扶服务创新)、政府治贫绩效概念模型,并运用281份问卷调查数据验证模型,以探寻互联网赋能对相对贫困治理的作用机理。研究发现,互联网赋能不仅对政府治贫绩效有显著的直接影响,而且以内部协同治贫、社会协同治贫和帮扶服务创新为中介间接影响政府治贫绩效;互联网赋能对内部协同治贫、社会协同治贫和帮扶服务创新有显著的直接影响;内部协同治贫、社会协同治贫和帮扶服务创新,对互联网赋能与政府治贫绩效的关系具有部分中介效应。论文从技术主导逻辑视角研究互联网赋能对相对贫困治理的作用机理,并提出“三化”治理路径,拓展了制度主导逻辑治贫理论,对中国特色反贫困理论进行了有益补充。

Establishment of Visual Fear Conditioning in Long-evans Rats

The neural mechanisms underlying visual information transmission and coding are currently attracting the attention of neuroscience and brain-like computing scholars.The subcortical visual pathway is known to affect fear emotion regulation via the amygdala;however an experimental paradigm for visual fear cognition training remains undefined.In this study,Long-Evans(LE)rats were used to develop an experimental training paradigm for visual cognition-associated fear conditioning based on the Pavlovian conditioning reflex.Simple images were shown on a unilateral screen(conditioned stimulus)were combined with electric foot shocks(unconditioned stimulus).We designed training paradigms and set up an estimated index using the rate of successful active escape.The training results were analyzed using a two-way ANOVA,and curve fitting was used to analyze the influence of decision time between the conditioned stimulus(CS)and unconditioned stimulus(US)on choice behavior.While neither the CS nor US had a significant effect on visual fear association training in LE rats,the decision time duration(CS-US)did have an impact on training.The method described here is most effective in establishing visual fear associations in rats when the(CS-UC)=10 s.This study describes a new experimental training paradigm for fear conditioning using visual stimuli and a quantitative evaluation standard according to the training mode of visual stimulation graphics.Moreover,it is an efficient paradigm for future study on visual information-processing mechanisms in the subcortical visual pathway during fear conditioning.

Chain-shattering Pt(IV)-backboned polymeric nanoplatform for efficient CRISPR/Cas9 gene editing to enhance synergistic cancer therapy

CRISPR/Cas9 system has become a promising gene editing tool for cancer treatment.However,development of a simple and effective nanocarrier to incorporate CRISPR/Cas9 system and chemotherapeutic drugs to concurrently tackle the biological safety and packaging capacity of viral vectors and combine gene editing-chemo for cancer therapy still remains challenges.Herein,a chain-shattering Pt(IV)-backboned polymeric nanoplatform is developed for the delivery of EZH2-targeted CRISPR/Cas9 system(NPCSPt/pEZH2)and synergistic treatment of prostate cancer.The pEZH2/Pt(II)could be effectively triggered to unpack/release from NPCSPt/pEZH2 in a chain-shattering manner in cancer cells.The EZH2 gene disruption efficiency could be achieved up to 32.2%of PC-3 cells in vitro and 21.3%of tumor tissues in vivo,leading to effective suppression of EZH2 protein expression.Moreover,significant H3K27me3 downregulation could occur after EZH2 suppression,resulting in a more permissive chromatin structure that increases the accessibility of released Pt(II)to nuclear DNA for enhanced apoptosis.Taken together,substantial proliferation inhibition of prostate cancer cells and further 85.4%growth repression against subcutaneous xenograft tumor could be achieved.This chain-shattering Pt(IV)-backboned polymeric nanoplatform system not only provides a prospective nanocarrier for CRISPR/Cas9 system delivery,but also broadens the potential of combining gene editing-chemo synergistic cancer therapy.

Pigeon Robot for Navigation Guided by Remote Control:System Construction and Functional Verification

Animal robots have outstanding advantages over traditional robots in their own energy supplies,orientation,and natural concealment,delivering significant value in the theories and applications of neural science,national security,and other fields.Presently,many animal robots have been fabricated,but researches about the applications of avian robots are still lacking.In this study,we constructed a Pigeon Robot System(PRS),optimized the electric stimulation parameters,assessed the electric stimulus of navigation,and evaluated the navigation efficiency in the field.Biphasic pulse constant current pattern was adapted,and the optimal stimulus parameters of 4 nuclei tested were of amplitude 0.3 mA,5 pulse trains,frequency 25 Hz,5 pulses,and a 25%duty cycle.Effective ratio of left and right steering behavior response to electric stimulus dorsointermedius ventralis anterior nuclei was 67%and 83%,respectively(mean value 75%).Electrical stimulation efficiency was 0.34-0.68 and path efficiency was 0.72-0.85 among pigeon robot individuals in the open field.Neither electrical stimulation efficiency nor path efficiency differed significantly(P>0.05),suggesting that the navigational PRS performance was not biased in either direction.PRS can achieve continuous navigation along simple pathways and provide the necessary application infrastructure and technical reference for the development of animal robot navigation technology.

Synergistic enhancement of immunological responses triggered by hyperthermia sensitive Pt NPs via NIR laser to inhibit cancer relapse and metastasis

The combination of tumor ablation and immunotherapy is a promising strategy against tumor relapse and metastasis.Photothermal therapy(PTT)triggers the release of tumor-specific antigens and damage associated molecular patterns(DAMPs)in-situ.However,the immunosuppressive tumor microenvironment restrains the activity of the effector immune cells.Therefore,systematic immunomodulation is critical to stimulate the tumor microenvironment and augment the anti-tumor therapeutic effect.To this end,polyethylene glycol(PEG)-stabilized platinum(Pt)nanoparticles(Pt NPs)conjugated with a PD-L1 inhibitor(BMS-1)through a thermo-sensitive linkage were constructed.Upon near-infrared(NIR)exposure,BMS-1 was released and maleimide(Mal)was exposed on the surface of Pt NPs,which captured the antigens released from the ablated tumor cells,resulting in the enhanced antigen internalization and presentation.In addition,the Pt NPs acted as immune adjuvants by stimulating dendritic cells(DCs)maturation.Furthermore,BMS-1 relieved T cell exhaustion and induced the infiltration of effector T cells into the tumor tissues.Thus,Pt NPs can ablate tumors through PTT,and augment the anti-tumor immune response through enhanced antigen presentation and T cells infiltration,thereby preventing tumor relapse and metastasis.