Characterizing Molecules and Circuits of Intermediate-Term Memory in Drosophila Brain( I )

One central goal in the neuroscience field is to understand how the memory information processed and stored within a complete brain. However, the human brain is too complicate and the genetic manipulation tools are absent to let us study it directly. Here, we use Drosophila melanogaster as an ideal model to understand this issue in terms of gene-gene interactions and neuron-neuron activities to memory. Flies can be trained to avoid a specific odor (the conditioned stimulus, CS) that is paired with negative reinforcement such as electric shock (the unconditioned stimulus, US). Mushroom body (MB), the physiological function is similar to the hippocampus in human, is a paired neuropils composed of about ~2500 neurons in each brain hemisphere. The dendrites of MB form calyx and project their axons anteriorly to form the αβ, α´β´ and γ lobes in the middle fly brain. Ample studies in behavior and brain-anatomy of fly have identified the MBs as crucial to olfactory learning and memory. A single training session produces robust memory that could persist several hours. 3-hour after single conditioning is referred to as intermediate-term memory, which is comprised by a labile anesthesia-sensitive memory (ASM) and a consolidated anesthesia-resistant memory (ARM), each account about half of memory retention score. So far, the detailed mechanism of ASM and ARM formation is still unclear. In our prior study, we have identified the functional NMDA receptors in MB are required for ASM formation. Dorsal Paired Medial (DPM), is a paired of neurons which soma located at the dorsal medial protocerebrum and extending their fibers to the whole MB. Behavioral evidences have shown that the DPM neurons secrete AMNESIAC neuropeptide to regulate ASM consolidation. However, the upstream circuits of the DPM neuron remain unknown. In our recent studies, we have identified the gap-junctional communication between the DPM and Anterior Paired Lateral (APL) neurons. Genetic disrupting the gap junction’s connections in APL and DPM neurons abolished ASM, while leaving ARM intact, which leads us propose a recurrent α′β′ KC–APL–DPM–α′β′ KC neuronal loop for sustain of ASM consolidation. In addition to ASM, our recent results have indicated that chemical neurotransmission from the APL neuron after learning is necessary for ARM consolidation, and unexpectedly octopamine, the counterpart of human norepinephrine, but not GABA underlies this synaptic transmission. We postulate that the unrevealed octopamine receptor(s) should reside in α´β´ KCs, since our preliminary data shows the axon of APL neurons preferentially innervates to the α´β´ MB neurons. These results suggest a novel neural pathway that, after conditioning, the APL neurons release octopamine onto α´β´ KCs for ARM formation in Drosophila brain. We will further investigate the following issues: (1) To identify which type(s) of octopamine receptor in MB underlying the ARM formation. (2) To confirm the dual role of APL neurons in ASM and ARM, by combinatorial manipulation of gap-junctional communication and/or octopamine biosynthesis. (3) To determine the chemical synaptic transmissions in which MB subregion(s) is required for ASM or ARM. (4) To test whether gap junctional communications between different subsets of MB are necessary for the formation of ARM or ASM. (5) To test the concept of ASM mnemonic reverberation in the α′β′ KC–APL–DPM–α′β′ KC neuronal network. (6) To monitor the sensitivity and 3-hour cellular memory traces of MB, APL neurons, and DPM neurons. It is anticipated that the results obtained from the above studies will help us understand more on how the memory processed in a complete brain.

Project ID:PC10109-0137
External Project ID:NSC101-2321-B182-010