Multi-Site Analysis of Hippocampal Neuronal Ensembles

海马神经元群的多位点分析

• 批准号: 7752796
• 负责人: JAMES J KNIERIM
• 金额: $ 35.3万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7752796
• 关键词: Accounting; Address; Alzheimer' s Disease; Amnesia; Animal Model; Animals; Area; Binding; Biological Models; Biological Neural Networks; Brain; Brain Diseases; Brain region; Cells; Cognitive; Complex; Conscious; Cues; Data; Disease; Dissociation; Distal; Dorsal; Electrodes; Epilepsy; Episodic memory; Event; Head; Hippocampal Formation; Hippocampus (Brain); Human; Individual; Information Systems; Injury; Knowledge; Lateral; Lesion; Life; Location; Medial; Memory; Memory Loss; Nature; Neurons; Operative Surgical Procedures; Patients; Pattern; Pharmacologic Substance; Play; Process; Property; Rattus; Recurrence; Relative (related person); Resolution; Role; Rotation; Series; Services; Site; Stream; Stroke; Structure; Symptoms; Syndrome; System; Techniques; Testing; Traumatic Brain Injury; Work; base; cognitive neuroscience; density; dentate gyrus; entorhinal cortex; experience; information organization; information processing; insight; memory retrieval; parallel processing; relating to nervous system; research study; response; treatment strategy

DESCRIPTION (provided by applicant): The hippocampus is a brain structure that is critical for forming and retaining long-term, episodic memories. Damage to the hippocampus from Alzheimer's Disease, stroke, epilepsy, or traumatic brain injury causes a profound amnesic syndrome in which patients are unable to form lasting memories of the everyday events of their lives. Converging evidence from humans and animal models suggests that the hippocampus integrates information from two parallel processing streams, which convey information about spatial location (context) and about individual objects or items, to create conjunctive representations of objects in place (or events in context). This proposal will investigate the organization of the flow of information through these parallel processing streams into the hippocampus, as well as the interaction of these streams with intrahippocampal processing of the CA3 and CA1 regions. Prior work on hippocampal place cells of rats has demonstrated a dissociation between the hippocampal CA3 and CA1 fields in terms of the coherence of ensemble spatial representations when local cues and global landmarks are pitted against each other. CA3 demonstrated a more coherent representation than CA1, in that the place fields tended to be controlled coherently by the local cues, whereas CA1 representations split into local- and global-landmark dominated ensembles. This proposal will test a series of hypotheses regarding the anatomical flow of information into the CA3 and CA1 regions that may account for the different responses of these regions. Multi-electrode techniques will be used to record the activity of neurons in different parts of the CA3 and CA1 regions and their input structures, including the entorhinal cortex and subicular complex (parasubiculum and presubiculum) in freely behaving rats. Local and global cues sets will be altered to test whether different parts of the hippocampal formation are preferentially bound to local or global frames of reference, and whether the known anatomical projections among these areas can account for the differential responses of CA3 and CA1 ensembles to these manipulations. These experiments will generate great insight into the nature of information processing and the organization of information flow into and through the hippocampal system, information that is critical toward understanding the computations performed by the hippocampus in the service of episodic memory. Such fundamental knowledge may be crucial for devising treatment strategies to ameliorate the devastating symptoms of hippocampal amnesia and to target selective sites for potential pharmaceutical or surgical therapies for these disorders. Profound memory loss is a hallmark of such degenerative brain disorders as Alzheimer's Disease, which originates in an area called the entorhinal cortex, progresses into the hippocampus, and eventually progresses throughout the brain's cortical regions. The experiments in this proposal will address fundamental issues regarding the nature of information processing and functions in the entorhinal cortex and hippocampus, generating insight into how these brain regions work normally and how they may go awry when the regions are damaged by Alzheimer's epilepsy, stroke, or traumatic injury.

描述(申请人提供)：海马体是一种大脑结构，对形成和保持长期的情景记忆至关重要。阿尔茨海默氏症、中风、癫痫或创伤性脑损伤对海马体的损害会导致严重的健忘症，患者无法对生活中的日常事件形成持久的记忆。来自人类和动物模型的聚合证据表明，海马体整合了来自两个并行处理流的信息，这两个流传达了关于空间位置(上下文)和关于单个对象或物品的信息，以创建对适当位置的对象(或上下文中的事件)的合取表示。这项建议将调查通过这些并行处理流进入海马体的信息流的组织，以及这些流与CA3和CA1区的海马区内处理的相互作用。先前对大鼠海马区细胞的研究表明，当局部线索和全局地标相互竞争时，海马区CA3和CA1区之间存在分离，表现为整体空间表征的一致性。CA3比CA1表现出更连贯的表征，因为位置场倾向于被局部线索连贯地控制，而CA1表征分裂成局部和全局地标主导的集合。这一提议将检验一系列关于信息流进入CA3和CA1区域的解剖学假说，这些假说可能解释这些区域的不同反应。多电极技术将被用来记录自由行为大鼠CA3和CA1区不同部分及其输入结构的神经元的活动，包括内嗅皮层和下丘下区复合体(下丘旁和丘前)。局部和全局线索集将被改变，以测试海马结构的不同部分是否优先与局部或全局参照系结合，以及这些区域之间的已知解剖投影是否可以解释CA3和CA1集合对这些操作的不同反应。这些实验将对信息处理的性质以及流入和通过海马体系统的信息流的组织产生巨大的洞察力，这些信息对于理解海马体在情景记忆服务中执行的计算至关重要。这些基础知识对于设计治疗策略以改善海马健忘症的破坏性症状以及为这些疾病的潜在药物或手术治疗选择靶点可能是至关重要的。严重的记忆力丧失是阿尔茨海默病等退行性大脑疾病的标志，阿尔茨海默病起源于内嗅皮层，进展到海马体，最终进展到整个大脑皮层区域。这项提案中的实验将解决与内嗅觉皮质和海马体的信息处理和功能的性质有关的基本问题，从而深入了解这些大脑区域是如何正常工作的，以及当这些区域受到阿尔茨海默氏症癫痫、中风或创伤损伤时，它们可能会出现错误。