The Drosophila connectome is the complete list of connections between neurons (commonly referred to as the "connectome") in the Drosophila melanogaster (fruit fly) nervous system. The Drosophila connectome has been completed for the female adult brain,[1][unreliable source] the male nerve cord,[2][unreliable source] and the larval stage.[3] The female fruit fly brain contains 127,978 neurons (for the first adult neuronal wiring diagram), and 3,016 neurons for the larval brain.So the synapse count is available for adults and larvae, and for the larvae it's the much lower number of roughly 548,000. The connectome is the most complex full one yet mapped, before mapped for only three other simpler organisms, first the C. elegans. The connectomes have been obtained by the methods of neural circuit reconstruction; Many of the 76 compartments of the Drosophila brain had connectomes available before the publication of the full connectome.
Why Drosophila
Connectome research (connectomics) has a number of competing objectives. On the one hand, investigators prefer an organism small enough that the connectome can be obtained in a reasonable amount of time. This argues for a small creature. On the other hand, one of the main uses of a connectome is to relate structure and behavior, so an animal with a large behavioral repertoire is desirable. It's also very helpful to use an animal with a large existing community of experimentalists, and many available genetic tools. Drosophila looks very good on these counts:
The brain contains about 135,000 neurons,[4] small enough to be currently reconstructed .[5]
The fruit fly exhibits many complex behaviors. Hundreds of different behaviors (feeding, grooming, flying, mating, learning, and so on) have been qualitatively and quantitatively studied over the years.
The genetics of the fruit fly are well understood, and many (tens of thousands) of genetic variants are available.
There are many electrophysiological, calcium imaging, and other studies ongoing with Drosophila.
Structure of the fly connectome
Adult brain
In 2023, the full connectome (for a female) was published: "we present the first neuronal wiring diagram of a whole adult brain, containing 5x10^7 chemical synapses between ~130,000 neurons reconstructed from a female Drosophila melanogaster. [..] The technologies and open ecosystem of the FlyWire Consortium set the stage for future large-scale connectome projects in other species."[1]Aprojectome, a map of projections between regions, can be derived from the connectome.
Before in 2011, a high-level connectome, at the level of brain compartments and interconnecting tracts of neurons, for the full fly brain was published.[6] A version of this is available online.[7]
Detailed circuit-level connectomes exist for the lamina[8][9] and a medulla[10] column, both in the visual system of the fruit fly, and the alpha lobe of the mushroom body.[11]
In May of 2017 a paper published in bioRxiv presented an electron microscopy image stack of the whole adult female brain at synaptic resolution. The volume is available for sparse tracing of selected circuits.[12][13]
In 2020, a dense connectome of half the central brain of Drosophila was released,[14][unreliable source] along with a web site that allows queries and exploration of this data.[15] The methods used in reconstruction and initial analysis of the connectome followed.[16]
Adult ventral nerve cord
In 2022, a group of scientists mapped the motor control circuits of the ventral nerve cord of a female fruit fly using electron microscopy.[17]
Larval brain
In 2023, Michael Winding et al. published a complete larval brain connectome.[18][3] This connectome was mapped by annotating the previously collected electron microscopy volume.[19] They found that the larval brain was composed of 3,016 neurons and 548,000 synapses. 93% of brain neurons had a homolog in the opposite hemisphere. Of the synapses, 66.6% were axo-dendritic, 25.8% were axo-axonic, 5.8% were dendro-dendritic, and 1.8% were dendro-axonic.
To study the connectome, they treated it as a directed graph with the neurons forming nodes and the synapses forming the edges. Using this representation, Winding et al found that the larval brain neurons could be clustered into 93 different types, based on connectivity alone. These types aligned with the known neural groups including sensory neurons (visual, olfactory, gustatory, thermal, etc), descending neurons, and ascending neurons.
The authors ordered these neuron types based on proximity to brain inputs vs brain outputs. Using this ordering, they could quantify the proportion of recurrent connections, as the set of connections going from neurons closer to outputs towards inputs. They found that 41% of all brain neurons formed a recurrent connection. The neuron types with the most recurrent connections were the dopaminergic neurons (57%), mushroom body feedback neurons (51%), mushroom body output neurons (45%), and convergence neurons (42%) (receiving input from mushroom body and lateral horn regions). These neurons, implicated in learning, memory, and action-selection, form a set of recurrent loops.
Structure and behavior
A natural question is whether the connectome will allow simulation of the fly's behavior. However, the connectome alone is not sufficient. Additional information needed includes gap junction varieties and locations, identities of neurotransmitters, receptor types and locations, neuromodulators and hormones (with sources and receptors), the role of glial cells, time evolution rules for synapses, and more.[20][21]
The fruit fly connectome has been used to identify an area of the fruit fly brain that is involved in odor detection and tracking. Flies choose a direction in turbulent conditions by combining information about the direction of air flow and the movement of odor packets. Based on the fly connectome, processing must occur in the “fan-shaped body” where wind-sensing neurons and olfactory direction-sensing neurons cross.[22][23]
^Takemura SY, Hayworth KJ, Huang GB, Januszewski M, Lu Z, Marin EC, et al. (2023). "A Connectome of the Male Drosophila Ventral Nerve Cord". bioRxiv. doi:10.1101/2023.06.05.543757. 2023-06.
^ abWinding M, Pedigo BD, Barnes CL, Patsolic HG, Park Y, Kazimiers T, et al. (March 2023). "The connectome of an insect brain". Science. 379 (6636): eadd9330. doi:10.1126/science.add9330. PMID36893230.
^
Meinertzhagen IA, O'Neil SD (March 1991). "Synaptic organization of columnar elements in the lamina of the wild type in Drosophila melanogaster". The Journal of Comparative Neurology. 305 (2): 232–263. doi:10.1002/cne.903050206. PMID1902848. S2CID35301798.
^Xu CS, Januszewski M, Lu Z, Takemura SY, Hayworth KJ, Huang G, et al. (2020). "A connectome of the adult Drosophila central brain". bioRxiv10.1101/2020.01.21.911859.
^Scheffer LK, Meinertzhagen IA (November 2021). "A connectome is not enough - what is still needed to understand the brain of Drosophila?". The Journal of Experimental Biology. 224 (21): jeb242740. doi:10.1242/jeb.242740. PMID34695211.
