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Genetic enhancement of learning and memory in rats

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Genetic enhancement of learning and memory in rats

中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： joe z.tsien Shanghai Institute of Brain Functional Genomics the Key Laboratories of OE and SSTCEast China Normal University Center for Systems Neurobiology Departments of Pharmacology and Biomedical EngineeringBoston University

＜正＞A lot of studies have demonstrated that NMDAR play an important role in regulating neuronal communication and synaptic function in the *** NMDARs are composed of NR1,NR2（A,B,C,and D）,and NR3（A and B） *** adult forebrain regions including the hippocampus and cortex,NR2A and NR2B subunits are predominant to form the NMD A receptor complex with NR1 *** has shown that NR2B subunit is a crucial molecule in controlling the threshold of synaptic plasticity and learning and memory in the mouse *** does NR2B subunit represent a universal molecular switch in gating the level of synaptic plasticity and memory function in the adult brain? In the present study,we investigated the role of NR2B gene in synaptic plasticity of hippocampus and memory in NR2B transgenic long evans rats by using combination of electrophysiological and behavioral *** main results are as follows:（1） There is no significant difference in basal synaptic transmission and PPF between transgenic and wild-type hippocampal slice,suggesting that both presynaptic function and postsynaptic AMPA receptors are normal in these transgenic animals. （2） NMDA-mediated LTP evoked by titanic stimulation is significantly larger in transgenic slices than in Wt slices and the overexpression of NR2B subunit is responsible for enhanced LTP in Tg ***2B Transgenic rats exhibited better spatial reference and spatial working memory in water maze and T-maze ***,it is concluded that the NR2B subunit serves as a crucial gating switch for controlling learning and memory functions across different animal species.

关键词： NR2B subunit hippocampus LTP memory

NMDA receptors are not required for pattern completion during associative memory recall

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NMDA receptors are not required for pattern completion durin...

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： joe z.tsien Shanghai Institute of Brain Functional Genomics Key Lab of Brain Functional GenomicsMOE ＆ STCSMEast China Normal University3663 North Zhongshan Rd.

＜正＞Objective The hippocampal parallel excitatory pathways referred to as the trisynaptic pathway（entorhinal cortex→dentate gyrus→CA3→CAl） and the monosynaptic pathways（entorhinal cortex→CAl,entorhinal cortex→CA3）.The hippocampal function has been analyzed by deleting the NMDA receptor gene NR1 at each stage of the trisynaptic circuit with Cre-loxP recombination *** completion,the process of retrieving entire memories from partial or degraded cues,was claimed to require NMDA receptors in the *** CA3 subregion,along with the dentate gyrus and CAl,presents all the functional characteristics that could be essential for this cognitive ***,such notion was derived from a CA3-specific NMDA receptor knockout mice exhibited performance deficit during the recall of spatial reference memory under the partial-cue condition. While this result carried a significant caveat that the gene knockout applied in that study lacked inducible temporal manipulations,and as a result,the NMDA receptors were absent in all stages of memory *** multiplicity of NMDA receptors function in acquisition,consolidation,retrieval and retention has remained obscure,it is possible that the performance deficit observed in CA3-specific knockout mice under the partial-cue condition might have well reflected weak binding of various memory traces during the acquisition and consolidation stages due to the lack of the NMDA receptors during those *** is conceivable that weak memory traces formed during learning may not be obvious under the full-cue recall condition,but became detectable under the partial-cue recall *** pattern completion deficit during recall may lead to a false interpretation that the NMDA receptors in the hippocampus are required for associative memory *** study therefore aims to examine the role of the NMDA receptors in pattern completion via transient knockout of NMDA receptors limited to the memory retrieval ***

关键词： pattern completion hippocampus NMDA receptor gene knockout spatial memory

Balanced dopamine is critical for pattern completion during associative memory recall

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Balanced dopamine is critical for pattern completion during ...

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： L.Phillip WANG joe z.tsien Brain and Behavior Discovery Institute Medical College of GeorgiaAugustaGeorgiaUnited States of America

＜正＞Objective Pattern completion,the ability to retrieve complete memories initiated by partial cues,is a critical feature of the *** study investigates the role of dopamine in memory *** We have analyzed dopamine transporter heterozygous knockout mice（DAT+/2）.Results（1） While these mice possess normal learning,consolidation,and memory recall under full cue conditions,they exhibit specific deficits in pattern completion under partial cue condition;（2） This form of memory recall deficit in the dopamine transporter heterozygous knockout mice can be reversed by a low dose of the dopamine antagonist haloperidol,further confirming that the inability to retrieve memory patterns is a result of dopamine *** Our results reveal that a delicate control of the brain’s dopamine level is critical for pattern completion during associative memory recall.

关键词： memory retrieval Dopamine pattern completion

Towards Transgenic Primates:What can we learn from mouse genetics?

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Science China(Life Sciences) 2009年第6期52卷 506-514页

作者： WANG Phillip L. tsien joe z. Brain and Behavior Discovery Institute School of MedicineMedical College of Georgia Yunnan Banna Primate Disease Model Research Center and Shanghai Institute of Brain Functional GenomicsKey Laboratory of Brain Functional GenomicsMOE & STCSMEast China Normal University

Considering the great physiological and behavioral similarities with humans,monkeys represent the ideal models not only for the study of complex cognitive behavior but also for the preclinical research and development of novel therapeutics for treating human *** powerful genetic tech-nologies initially developed for making mouse models are being explored for generating transgenic primate *** review the latest genetic engineering technologies and discuss the potentials and limitations for systematic production of transgenic primates.

关键词： Non-human primate Mouse Transgene Genetics Learning Memory disease model

On brain activity mapping: Insights and lessons from Brain Decoding Project to map memory patterns in the hippocampus

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Science China(Life Sciences) 2013年第9期56卷 767-779页

作者： tsien joe z. LI Meng OSAN Remus CHEN GuiFen LIN LongNian WANG Phillip Lei FREY Sabine FREY Julietta zHU DaJiang LIU TianMing zHAO Fang KUANG Hui Brain and Behavior Discovery Institute Medical College of Georgia Georgia Regents University Department of Mathematics and Institute of Neuroscience Georgia State University Department of Cell and Developmental Biology University College London Shanghai Institute of Brain Functional Genomics East China Normal University Department of Computer Science & Bioimaging Research Center The University of Georgia Brain Decoding Center Banna Biomedical Research Institute Xi-Shuang-Ban-Na Prefecture

The BRAIN project recently announced by the president Obama is the reflection of unrelenting human quest for cracking the brain code, the patterns of neuronal activity that define who we are and what we are. While the Brain Activity Mapping proposal has rightly emphasized on the need to develop new technologies for measuring every spike from every neuron, it might be helpful to consider both the theoretical and experimental aspects that would accelerate our search for the organizing principles of the brain code. Here we share several insights and lessons from the similar proposal, namely, Brain Decoding Project that we initiated since 2007. We provide a specific example in our initial mapping of real-time memory traces from one part of the memory circuit, namely, the CA1 region of the mouse hippocampus. We show how innovative behavioral tasks and appropriate mathematical analyses of large datasets can play equally, if not more, important roles in uncovering the specific-to-general feature-coding cell assembly mechanism by which episodic memory, semantic knowledge, and imagination are generated and organized. Our own experiences suggest that the bottleneck of the Brain Project is not only at merely developing additional new technologies, but also the lack of efficient avenues to disseminate cutting edge platforms and decoding expertise to neuroscience community. Therefore, we propose that in order to harness unique insights and extensive knowledge from various investigators working in diverse neuroscience subfields, ranging from perception and emotion to memory and social behaviors, the BRAIN project should create a set of International and National Brain Decoding Centers at which cutting-edge recording technologies and expertise on analyzing large datasets analyses can be made readily available to the entire community of neuroscientists who can apply and schedule to perform cutting-edge research.

关键词： BRAIN project Brain Decoding Project brain activity map learning and memory episodic memory semantic knowledge imagination concepts fear conditioning earthquake experiences neural code

Double gallstone ileus

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Hepatobiliary & Pancreatic Diseases International 2008年第4期7卷 437-439页

作者： Aamir z Khan joe Nariculum Stefano M Andreani Adam Stacey-Clear Department of Surgery East Surrey Hospital Canada AvenueRedhillSurreyRH1 5RHUK Whipps Cross Hospital LeytonstoneUK

BACKGROUND:Gallstone ileus remains a rare but important cause of intestinal obstruction. METHOD:We present a unique case of two gallstones causing intestinal obstruction at the same time. RESULTS:A 90-year-old lady presented with signs and symptoms of small bowel *** operation,two gallstones stuck at different points within the bowel were causing the obstruction and were removed. CONCLUSION:When operating on patients with small bowel obstruction from gallstone ileus,examination of the entire small bowel should be considered mandatory.

关键词： gallstones intestinal obstruction ileus

Neuronal coding in dorsal media and dorsal lateral striatum during habit-learning

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Neuronal coding in dorsal media and dorsal lateral striatum ...

中国神经科学学会第十二届全国学术会议

作者： Deheng Wang Hongmiao zhang joe tsien School of Basic Medicine Shanghai University of Traditional Chinese Medicine Brain and Behavior Discovery Institute and Department of Neurology Medical College of Georgia Augusta University School of Mechanical and Electric Engineering Soochow University

Dorsal striatum has been shown to contribute to goal-directed behavior and habit-learning, but two major sub-regions of dorsal striatum in rodents may involve in different stage of habit-learning. Using plus-maze task in which rodents learned fixed running path to achieve the sugar pellet, we uncovered the neuronal activity of the dorsal striatum develop place-related activity –related to the maze "running initiation, turning and destination". Also, the population neurons had dynamic network change when the mice perform the plus-maze during these training days. Furthermore, the firing of dorsolateral striatum units showed higher correlation after plus-maze overtraining compared to dorsomedial striatum which suggesting that the dorsolateral striatum（DLS）is implicated in habit formation while the dorsomedial striatum（DMS） is thought to be involved in the goal-directed behavior.

关键词： Neuronal coding DMS DLS Striatum Habit-learning

UHV/CVD Low-Temperature Si Epitaxy Used for SiGe HBT

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Journal of Rare Earths 2004年第z2期22卷 30-34页

作者： Huang Wentao Shen Guanhao Li Xiyou Chen Changchun zhang Wei Liu zhihong Chen Peiyi tsien Peihsin Institute of Microelectronics Tsinghua UniversityBeijing 100084China

Low-temperature-epitaxy n-type silicon layers were grown on arsenic-doped n+-type silicon substrate by using ultra-high vacuum chemical vapor deposition (UHV/CVD). The transition region thickness of the Si layers grown under different PH3 flux and different growth temperature were investigated by spreading resistance probe. Results showed that the growth temperature had remarkable influence on the arsenic diffusion from the Si substrate. The thicknesses of the transition region were 0.16 μm grown at 700 ℃ and 0.06 μm grown at 500 ℃, respectively. Moreover, the dopant profiles were very abrupt. X-ray diffraction investigation of the epitaxial Si layer showed the quality of Si layer was very *** e HBT device was fabricated by using a revised double-mesa polysilicon-emitter process. Tests show that the CB-junction breakdown characteristic of the SiGe HBT is very hard, and the leakage current is only 0.3 μA under a reverse voltage of - 14.0 V. The SiGe HBT device had also good output performance, and the current gain is 60.

关键词： UHV/CVD low temperature Si epitaxy dopant profile SiGe HBT

The new era of cardiovascular research:revolutionizing cardiovascular research with 3D models in a dish

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Medical Review 2024年第1期4卷 68-85页

作者： Yuan Yang Hao Yang Fedir N.Kiskin joe z.zhang Institute of Neurological and Psychiatric Disorders Shenzhen Bay LaboratoryShenzhenGuangdong ProvinceChina Institute of Neurological and Psychiatric Disorders Shenzhen Bay LaboratoryShenzhen 518132Guangdong ProvinceChina

Cardiovascular research has heavily relied on studies using patient samples and animal ***,patient studies often miss the data from the crucial early stage of cardiovascular diseases,as obtaining primary tissues at this stage is *** animal models can offer some insights into disease mechanisms,although they usually do not fully recapitulate the phenotype of cardiovascular diseases and their *** recent years,a promising breakthrough has emerged in the form of in vitro three-dimensional(3D)cardiovascular models utilizing human pluripotent stem *** innovative models recreate the intricate 3D structure of the human heart and vessels within a controlled *** advancement is pivotal as it addresses the existing gaps in cardiovascular research,allowing scientists to study different stages of cardiovascular diseases and specific drug responses using human-origin *** this review,we first outline various approaches employed to generate these *** then comprehensively discuss their applications in studying cardiovascular diseases by providing insights into molecular and cellular changes associated with cardiovascular ***,we highlight the potential of these 3D models serving as a platform for drug testing to assess drug efficacy and *** their immense potential,challenges persist,particularly in maintaining the complex structure of 3D heart and vessel models and ensuring their function is comparable to real ***,overcoming these challenges could revolutionize cardiovascular *** has the potential to offer comprehensive mechanistic insights into human-specific disease processes,ultimately expediting the development of personalized therapies.

关键词： pluripotent stem cells three-dimensional(3D)models cardiac microtissues cardiac organoids vessel organoids organ-on-a-chip