The brain has the amazing capacity to form long-lasting memories, but the underlying neural mechanisms remain elusive. To address this issue, I will use the Drosophila olfactory system to examine the cellular mechanisms underlying the formation and maintenance of long-term odor- associated memories. Drosophila are capable of forming long-term memories (LTMs) with underlying molecular pathways and synaptic modifications similar to those seen in higher organisms. A large body of work has defined the Mushroom Body (MB) as the neural substrate for olfactory learning;these studies have also determined that genes involved in memory formation are expressed within this structure. The study of LTM in the Drosophila olfactory system is facilitated by the fact that only a small number of MB extrinsic neurons (MBEs) read out synaptic changes associated with learning in the MB. While there exists a wealth of knowledge on olfactory processing prior to reaching the MBEs, the MBEs themselves remain largely uncharacterized. Here, I address how odor-associative LTMs are encoded at identifiable synapses within MB circuits. This proposal makes use of the microcircuit of the ? lobe compartment of the MB, consisting of Kenyon Cell (KC) axons and MBE dendrites. I will employ multiple state-of-the-art methods, including in vivo electrophysiology from identified MBEs, single fly learning and memory assays, along with single-cell gene expression analysis, to achieve a holistic understanding of olfactory memory encoding. Studying odor processing and memory formation at cellular resolution is required for developing novel strategies for the treatment of cognitive and neurodegenerative disorders that impact memory formation or recall. Our studies will also shed new light on the complex processes the brain uses to encode sensory stimuli and modify behavior. Specifically, my proposal will address the following aims:
SPECIFIC AIM 1) To determine how odors are represented among a population of MB extrinsic neurons.
SPECIFIC AIM 2) To characterize the relationship between behavior and neural signatures of LTM within MB extrinsic neurons.
SPECIFIC AIM 3) To identify gene expression changes underlying olfactory LTM.
This research will shed light on how sensory information is represented in the brain, and how long-term memories are encoded within individual neurons. Due to the many similarities between the nervous systems of flies and mammals, this information can ultimately be related to mechanisms underlying odor coding and memory formation in humans. This study has the potential to provide novel molecular pathways and drug targets for diseases, such as Huntington's, Parkinson's, and Alzheimer's, and also to improve age dependent cognitive decline that is accompanied by both sensory and memory impairment.
