FUNCTIONAL CODING IN HIPPOCAMPAL/CORTICAL SYSTEMS

海马/皮质系统的功能编码

• 批准号: 7350345
• 负责人: Howard B. Eichenbaum
• 金额: $ 28.25万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7350345
• 关键词: Age; Age-associated memory impairment; Aging; Animals; Appearance; Area; Behavior; Behavioral; Biological; Cells; Code; Cognitive aging; Confusion; Development; Environment; Episodic memory; Exhibits; Failure; Familiarity; Fire - disasters; Funding; Goals; Hippocampus (Brain); Hyperactive behavior; Impaired cognition; Impairment; Lateral; Maze Learning; Measures; Memory; Memory impairment; Muscle Rigidity; Nature; Neurons; Odors; Other Finding; Pattern; Performance; Pharmaceutical Preparations; Pharmacological Treatment; Prefrontal Cortex; Process; Protocols documentation; Range; Rate; Rattus; Retrieval; Rodent Model; Signal Detection Analysis; System; Testing; Therapeutic; Therapeutic Agents; Water; age effect; age related; aged; base; design; entorhinal cortex; experience; improved; juvenile animal; loss of function; memory recognition; memory retrieval; neurophysiology; novel; programs; relating to nervous system; research study; success; young adult

Aging is associated with declining function across a broad spectrum of behavioral and biological measures. This component of the program project will pursue a combination of behavioral and neurophysiological studies aimed at characterizing the nature and range of alterations in neuronal representations associated with aging: Specific Aim 1: Extending on findings of the previous funding period, we will examine the development of new hippocampal spatial representations when animals are presented with a novel environment. Our previous studies indicated that CAS neurons selectively are hyperactive and are "rigid" in that they retrieve old representations rather than form new ones when experiencing a novel environment. These studies will examine the relationship between hyperactivity and rigidity of CAS cells and memory performance, and will examine the effects of putative memory enhancing drugs on hippocampal network activity. Specific Aim 2: Exploiting recent findings of hippocampal neuronal activity patterns closely associated with memory performance in young animals, we will characterize the nature of performance-related abnormalities in hippocampal representation associated with aging. These studies will determine whether trial-by-trial memory errors in a T-maze spatial delayed alternation task are associated with compromised stability of hippocampal spatial representations, retrieval of inappropriate memory representations, or failure to encode or retrieve trial specific representations. These studies will also examine the effects of putative memory enhancing drugs on memory-related neural activity patterns. Specific Aim 3: We will use recently developed protocol for distinguishing "recollection" and "familiarity" components of recognition memory to examine the nature of age-related cognitive deficits in our rodent model. We will also compare performance related activation of areas of the prefrontal cortex and hippocampal region in encoding and retrieval and loss of functions in these areas associated with aging. These studies will also examine the effects of putative memory enhancing drugs on component processes in recognition memory in aged rats. Each of these experiments is designed to test specific hypotheses about the nature of age-related cognitive decline and to identify and characterize pharmacological agents as targets of potential therapeutic value. Furthermore, comparisons of the results among these experiments, and with findings from the other projects, will identify features of cognitive aging and effects of therapeutic agents that are common or distinct across a range of behavioral tasks.

衰老与各种行为和生物学的功能下降有关 措施。该计划项目的这个组成部分将追求行为和 神经生理研究旨在表征神经元改变的性质和范围 与衰老相关的表示形式： 特定目的1：延长上一个资金期的发现，我们将研究 当动物带来新的环境时，新的海马空间表示。我们的 先前的研究表明，CAS神经元有选择地活跃，并且“刚性”是因为它们检索 旧表示，而不是在体验新的环境时形成新的表现。这些研究会 检查CAS细胞的多动症与刚性之间的关系与记忆性能，并将 检查假定的记忆增强药物对海马网络活性的影响。 特定目的2：利用与紧密相关的海马神经元活动模式的最新发现 年轻动物的记忆表现，我们将表征与性能相关异常的性质 在与衰老相关的海马表示中。这些研究将决定是否逐审 T迷宫空间延迟交替任务中的内存错误与受损的稳定性有关 海马空间表示，检索不适当的内存表示或未能编码 或检索特定于试验的表示。这些研究还将检查假定记忆的影响 增强与记忆有关的神经活动模式的药物。 特定目标3：我们将使用最近开发的协议来区分“回忆”和“熟悉度” 识别记忆的组成部分，以检查啮齿动物中与年龄相关的认知缺陷的性质 模型。我们还将比较前额叶皮层区域的性能与性能相关的激活 与衰老相关的这些区域中编码，检索和功能丧失的海马区域。 这些研究还将检查假定的记忆增强药物对组件过程的影响 老年大鼠的识别记忆。 这些实验中的每一个都旨在测试有关年龄相关性质的特定假设 认知能力下降，并识别和表征药理学剂作为潜在治疗的靶标 价值。此外，在这些实验中比较结果，以及与其他实验的发现 项目，将确定常见或不同的治疗剂的认知衰老和影响的特征 跨各种行为任务。