The complete connectome of a learning and memory centre in an insect brain

Abstract

Associating stimuli with positive or negative reinforcement is essential for survival, but a complete wiring diagram of a higher-order circuit supporting associative memory has not been previously available. Here we reconstruct one such circuit at synaptic resolution, the Drosophila larval mushroom body. We find that most Kenyon cells integrate random combinations of inputs but that a subset receives stereotyped inputs from single projection neurons. This organization maximizes performance of a model output neuron on a stimulus discrimination task. We also report a novel canonical circuit in each mushroom body compartment with previously unidentified connections: reciprocal Kenyon cell to modulatory neuron connections, modulatory neuron to output neuron connections, and a surprisingly high number of recurrent connections between Kenyon cells. Stereotyped connections found between output neurons could enhance the selection of learned behaviours. The complete circuit map of the mushroom body should guide future functional studies of this learning and memory centre.

Odor Perception on the Two Sides of the Brain: Consistency Despite Randomness

“…As in the piriform, glomerular inputs to the KCs show no apparent structure (Caron et al, 2013; Gruntman and Turner, 2013; Murthy et al, 2008). Further support for the random nature of these connections is provided by electron microscopy (EM) data from a Drosophila larva (Eichler et al, 2017), indicating that input connections to the KCs are not only unstructured, but are also completely different on the two sides of the brain. KCs synapse onto mushroom body output neurons (MBONs) that are analogous to the model readout we have introduced.…”

Comparative single-cell transcriptomics of complete insect nervous systems

“…Neural circuits are no exception. While recent advances in connectomics (1)(2)(3)(4)(5)(6)(7)(8)(9) and live imaging techniques (10)(11)(12)(13)(14) offer unprecedented information about neural connectivity and activity, the task of identifying cell types has traditionally relied on painstaking morphological, functional, or single gene histochemical taxonomy. High-throughput single-cell RNA sequencing (scRNAseq) offers a new way forward by providing a molecular-level identity for each cell via its transcriptomic profile.…”

“…These techniques have already revealed striking heterogeneity in cell populations that is lost in bulk samples. In the fruit fly, efforts are already well underway to produce connectomic (4)(5)(6)(7)9), activity (12)(13)(14), and behavior atlases (16)(17)) of the nervous system. Much work has separately revealed the role that genes (18)(19) and circuits (20)(21) play in behavior; a major challenge is to combine genes, circuits, and behavior all at once.…”

Learning with reward prediction errors in a model of the Drosophila mushroom body

“…6). In larval Drosophila, there are several examples of cross-compartmental DANs and MBONs (40), but a full account of the valence encoded by these neurons is yet to be provided.…”