Mechanisms for Consolidation and Retrieval of Drosophila Long-Term Memory

Memories make us who we are. Many people suffering from brain dysfunctions have difficulties even to remember and recognize themselves since the serious memory lost. The memory lost (amnesia) caused by aging, neurodegeneration, or diseases greatly affects the quality of life in the patients. Therefore, understanding how memories are formed and encoded in our brain will be one of the most important things in neuroscience field. There are several different types of memory have been described in human. The long-term memory (LTM) is a type of memories intended for storage of learned information for a long period of time. However, how the LTM is processed, consolidated, stored, and retrieved in the brain still a mystery. The human brain is too complex which contains more than 100-billion of neurons and more than trillion of synapses. Here, I propose to study LTM using Drosophila melanogaster, the fruit fly, as a model, where the relatively small brain (~130,000 neurons) with powerful and sophisticated genetic tools that allowed us to manipulate the functions in specific populations of brain neurons in a living animal. In our recent study, we found that thirsty flies can associate a specific odor with water to form water-reward memory and this memory persists for over 24 hours without any decay. Genetic and pharmacologic evidences indicate that this long-lasting water-reward memory belongs to LTM. The memory formation process can be classified into acquisition, consolidation, and retrieval. During acquisition, the water-responsive dopaminergic neurons PAM-β´1 conveyed water-reward signal to fly olfactory learning and memory center, the mushroom body (MB), whereas odor information is conveyed via projection neurons to MB. The neurotransmission in the MB α´β´ neurons is required for consolidation, whereas the neurotransmission in MB γ and αβ neurons is required for the retrieval of water-reward LTM (wLTM). However, the detailed neural circuits and molecular mechanisms are involved in wLTM consolidation and retrieval still uncertain. The goal of this proposed project is to comprehensively dissect the cellular and molecular mechanisms regarding the consolidation and retrieval of wLTM in the fly brain, which will pave the way for understanding the operational principles of human LTM. In this proposal, I outline these following specific aims:(1) Identify wLTM consolidation circuits and molecular mechanisms.(2) Identify wLTM retrieval circuits and molecular mechanisms.(3) Monitor neural activity during wLTM consolidation. (4) Monitor wLTM traces in the brain. (5) Propose working principles of wLTM in both molecular and circuit levels.

Project ID:PA10907-1272
External Project ID:MOST109-2326-B182-001-MY3