Single neuron biology, aging, and memory.

描述(申请人提供)：这项研究的目标是将果蝇大脑中单一类型神经元的生物学与其在记忆过程和衰老中的功能联系起来，以满足计划公告PA-11-320的指令：“开展单细胞生物学研究，以加强对正常衰老机制和与年龄相关的疾病的了解。”研究中的神经元背侧配对内侧神经元(DPM)在形态和功能上是独一无二的。苍蝇的大脑每个半球只有一个DPM神经元，先前的研究表明，这个神经元专门在记忆的特定时间阶段发挥作用，包括中长期记忆(ITM和LTM)。此外，该神经元的功能随着年龄的增长而退化，导致老年果蝇的ITM和LTM较差。因此，这种神经元提供了一个独特的机会，可以将单一类型神经元的生物学与衰老和因年龄而造成的记忆障碍联系起来。我们的研究将详细说明幼龄和老年果蝇的突触连接，以确定连接是否是认知障碍随年龄增长的基础。他们还将描绘DPM神经元随年龄增长的RNA群体，以揭示这种神经元类型中的基因表达如何随着年龄的变化而变化，以及被改变的特定基因可能如何导致可能的连接性变化和与年龄相关的记忆障碍。总体而言，这些研究将有助于理解衰老如何改变参与记忆特定阶段的特定类型神经元的结构和生理。鉴于与衰老相关的认知问题已经得到了充分的记录，这项研究具有丰富的医学意义。

DESCRIPTION (provided by applicant): The goal of this research is to relate the biology of a single type of neuron in the Drosophila brain to its function in memory processes and aging to meet the directives of Program Announcement PA-11-320: "Develop research on single cell biology to enhance the understanding of the mechanisms of normal aging and of age-related diseases." The neuron under study, the dorsal paired medial neuron (DPM), is unique in morphology and function. The fly brain has but one DPM neuron per hemisphere and prior studies have shown that this neuron functions specifically in specific temporal phases of memory, including intermediate- and long-term memory (ITM and LTM). Moreover, the function of this neuron degrades with aging, leading to poor ITM and LTM in aged flies. This neuron thus offers a singular opportunity to relate the biology of a single type of neuron to aging and memory impairment due to age. Our studies will detail the synaptic connections in young and aged flies to determine whether connectivity underlies the cognitive impairment with age. They will also profile the RNA population of the DPM neurons across age to reveal how gene expression within this neuron type is altered with age, and how specific genes that are altered may underlie possible connectivity changes and the age-related memory impairment. Overall, the studies will contribute significantly to an understanding of how aging alters the structure and physiology of a specific type of neuron that is involved in specific phases of memory. There is a rich medical importance to this research given the well-documented problems of cognition associated with aging.