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.
Aging occurs, in part, through changes at the cellular level that subsequently impact the functioning of individual organs and the body. Recently developed techniques now allow the scientist to query the changes that occur at the cellular level to gain an unprecedented view of the process of aging. This project will study a specific type of neuron that becomes dysfunctional with age, leading to impairments in memory. It will utilize the experimental model Drosophila melanogaster - because of the ease of studying memory formation in this organism, the ability to identify and isolate specific types of neurons of differnt ages with known roles in memory for study, and to peer into its brain and watch the activity of neurons during memory formation. The knowledge obtained from these studies will contribute to understanding how aging impacts the structure, physiology, and function of a specific type of neuron, leading to age-related memory loss.
