Single neuron biology, aging, and memory.

描述（由申请人提供）：本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的指示：“开展单细胞生物学研究，以增强对正常衰老和年龄相关疾病机制的理解。“研究中的神经元，背侧成对内侧神经元（dorsal pairing medial neuron，简称PNN），在形态和功能上都是独特的。果蝇大脑每个半球只有一个神经元，先前的研究表明，这个神经元在记忆的特定时间阶段起作用，包括中期和长期记忆（ITM和LTM）。此外，这种神经元的功能随着年龄的增长而下降，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，将单一类型神经元的生物学与衰老和由于年龄引起的记忆障碍联系起来。我们的研究将详细说明年轻和老年果蝇的突触连接，以确定连接是否是随着年龄增长的认知障碍的基础。他们还将对不同年龄的海马神经元的RNA群体进行分析，以揭示这种神经元类型中的基因表达如何随着年龄的增长而改变，以及改变的特定基因如何成为可能的连接变化和与年龄相关的记忆障碍的基础。总的来说，这些研究将大大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学。考虑到与衰老相关的认知问题，这项研究具有丰富的医学重要性。

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.