SSA Network analysis of entorhinal-hippocampal circuits for spatial cognition and memory
空间认知和记忆的内嗅-海马回路的 SSA 网络分析
基本信息
- 批准号:1959314
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:英国
- 项目类别:Studentship
- 财政年份:2017
- 资助国家:英国
- 起止时间:2017 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The ability to use information from the outside world, such as visual landmarks and local cues, to locate ourselves in space and to form memories for what happened where, is a fundamental cognitive function. It is known that the entorhinal cortex and hippocampus are required for these functions, but the precise entorhinal-hippocampal circuitry remains unknown. The proposed project will combine recording of neural activity in behaving mice with state-of-the-art molecular manipulations to establish the neural circuitry by which external information in the environment gains access to one of the primary representations of location in the mammalian brain - the hippocampal place cells.A basic property of hippocampal place cells is that the location of their firing fields is anchored to external cues, including both distal visual landmarks, and local cues (such as objects within the environment). It has recently been found that cells in the medial entorhinal cortex (MEC), many of which have spatial firing properties, are anchored to distal visual landmarks, whereas cells in the lateral entorhinal cortex (LEC) tend to fire in relation to local cues (Neunuebel et al, 2013). As the entorhinal cortex provides the main cortical input to the hippocampus, this leads to the hypothesis that distal visual landmark information and local cue information access the hippocampus from the MEC and LEC respectively. This is supported by published behavioural data from the Ainge lab showing that LEC lesions disrupt associative memory for objects and their locations (Wilson et al, 2013), and new unpublished data from the Wood lab in Edinburgh showing that hippocampal place cells of mice that have had neurotoxic lesions of the MEC do not follow distal cues, but instead are more likely to follow local cues. The aim of the project is to determine the precise inputs from MEC and LEC to the hippocampus by which visual landmarks and local cues influence both place cells and spatial behaviour. This will be achieved by making use of lines of mice that have been genetically engineered to express cre in specific populations of entorhinal cells, combined with targeted injections of cre-dependent viruses to express either Tetanus light chain toxin (TeLC) which blocks neurotransmitter release, or light activated channels, or DREADDS. These techniques will allow us to block the inputs from a specific cell population in MEC or LEC over long (TeLC), medium (DREADDS) or short (optogenetics) time frames. Preliminary experiments in the host labs are currently using this approach to inactivate stellate cells in layer 2 of the MEC (Wood lab) and LEC (Ainge lab). The proposed project will assess the effects of inhibiting these cell populations on a) hippocampal place field activity, and specifically their control by distal visual landmarks and local cues and b) spatial memory tasks in which distal or local cues must be associated with reinforced locations.
使用来自外部世界的信息,如视觉地标和当地线索,在空间中定位我们自己并形成对发生在哪里的记忆的能力,是一种基本的认知功能。众所周知,内嗅皮层和海马体是这些功能所必需的,但精确的内嗅觉-海马体回路仍不清楚。拟议的项目将结合记录行为小鼠的神经活动和最先进的分子操作来建立神经电路,通过该电路,环境中的外部信息可以访问哺乳动物大脑中主要的位置表示之一-海马区细胞。海马区细胞的一个基本特性是其激发区域的位置锚定于外部线索,包括远端视觉地标和局部线索(如环境中的物体)。最近发现,内侧内嗅皮层(MEC)中的细胞,其中许多具有空间放电特性,固定在远端视觉地标上,而外侧内嗅皮层(LEC)中的细胞倾向于与局部线索有关的放电(Neunuebel等,2013)。由于内嗅皮层为海马区提供了主要的皮质输入,这导致了远端视觉标志信息和局部线索信息分别从MEC和LEC进入海马区的假设。这得到了来自Ainger实验室的已发表的行为数据的支持,该数据表明LEC损伤扰乱了对物体及其位置的联想记忆(Wilson等人,2013年),以及来自爱丁堡Wood实验室的新的未发表的数据表明,MEC神经毒性损伤的小鼠的海马区细胞不遵循远端线索,而更有可能遵循局部线索。该项目的目的是确定MEC和LEC对海马体的准确输入,通过这些输入,视觉地标和局部线索影响位置细胞和空间行为。这将通过利用基因工程的小鼠品系在特定的内嗅觉细胞群中表达cre,结合靶向注射依赖cre的病毒来表达破伤风轻链毒素(TEC)(阻止神经递质释放)或光激活通道(DREADD)来实现。这些技术将允许我们在长(TELC)、中(DREADD)或短(光遗传学)时间范围内阻止来自MEC或LEC中特定细胞群的输入。宿主实验室的初步实验目前正在使用这种方法来灭活MEC(Wood实验室)和LEC(Ainger实验室)第二层中的星状细胞。这项拟议的项目将评估抑制这些细胞群对a)海马场活动的影响,特别是远端视觉地标和局部线索对它们的控制,以及b)远端或局部线索必须与强化位置相关联的空间记忆任务。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
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专利数量(0)
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其他文献
吉治仁志 他: "トランスジェニックマウスによるTIMP-1の線維化促進機序"最新医学. 55. 1781-1787 (2000)
Hitoshi Yoshiji 等:“转基因小鼠中 TIMP-1 的促纤维化机制”现代医学 55. 1781-1787 (2000)。
- DOI:
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LiDAR Implementations for Autonomous Vehicle Applications
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
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吉治仁志 他: "イラスト医学&サイエンスシリーズ血管の分子医学"羊土社(渋谷正史編). 125 (2000)
Hitoshi Yoshiji 等人:“血管医学与科学系列分子医学图解”Yodosha(涉谷正志编辑)125(2000)。
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Effect of manidipine hydrochloride,a calcium antagonist,on isoproterenol-induced left ventricular hypertrophy: "Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,K.,Teragaki,M.,Iwao,H.and Yoshikawa,J." Jpn Circ J. 62(1). 47-52 (1998)
钙拮抗剂盐酸马尼地平对异丙肾上腺素引起的左心室肥厚的影响:“Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,
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