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The synapse-level wiring diagram of a center for learning and memory, the insect mushroom body

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SNA - Theoretical foundations for statistical network analysis

Associating stimuli with positive or negative outcomes is essential for survival, but a complete wiring diagram of a higher-order circuit supporting associative memory has not been previously available. In this talk, I will discuss our findings—in collaboration with Marta Zlatic, Andreas Thum and Larry F. Abbott—on circuits for associative memory based on the full reconstruction at synaptic resolution of one such circuit, the insect mushroom body (MB), as mapped in the larva of Drosophila. Our results provide single-animal cross-hemispheric evidence that Kenyon cells (KCs)—the parallel fibers—integrate random combinations of stimuli, but we also found a set of KCs that are wired in an ordered way to relay signals from single projection neurons (PNs).   We show that combining these two kinds of KCs maximizes the dimension of the odor representation. Memories are formed when co-activation of KCs and modulatory neurons (mostly dopaminergic, DAN ) alters the strength of KC synapses onto MB output neurons (MBONs) within discrete MB regions known as compartments.  We found a novel canonical circuit in these compartments with previously unpredicted connections: a reciprocal KC-to-DAN connection and a DAN -to-MBON connection, suggesting multiple potential sites of synaptic plasticity.  Counting of individual synaptic connections allowed us to assess the relative contributions of olfactory, non-olfactory, modulatory and extra-MB signals onto each MBON , providing evidence that MBO Ns contextualize associative memories with a variety of other information. We also found a stereotyped MBON -MBON circuit with reciprocal inhibition among MB compartments of opposing valences suggestive of competitive interactions that could enhance the selection of learned response. Finally, feedback connections from MBO Ns to neuromodulatory neurons provide a possible mechanism for existing memories to affect the formation of new ones. The complete circuit map of the MB should guide future functional studies of this center of learning and memory.



This talk is part of the Isaac Newton Institute Seminar Series series.

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