Biology:Drosophila connectome

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Short description: Connection graph of the brain of the fruit fly Drosophila melanogaster

A Drosophila connectome is a list of neurons in the Drosophila melanogaster (fruit fly) nervous system, and the chemical synapses between them. The fly's nervous system consists of the brain plus the ventral nerve cord, and both are known to differ considerably between male and female.[1][2] Dense connectomes have been completed for the female adult brain,[3] the male nerve cord,[4] and the female larval stage.[5] The available connectomes show only chemical synapses - other forms of inter-neuron communication such as gap junctions or neuromodulators are not represented. Drosophila is the most complex creature with a connectome, which had only been previously obtained for three other simpler organisms, first C. elegans. The connectomes have been obtained by the methods of neural circuit reconstruction, which over the course of many years worked up through various subsets of the fly brain to the almost full connectomes that exist today.

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 meets all of these requirements:

  • The brain contains about 135,000 neurons,[6] small enough to be currently reconstructed.[7]
  • 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

The one fully-reconstructed adult female fruit fly brain contains about 128,000 neurons and roughly 50 million chemical synapses, and the single reconstructed male nerve cord has about 23,000 neurons and 70 million synapses. These numbers are not independent, since both the brain and the nerve cord contain portions of the several thousand ascending and descending neurons that run through the neck of the fly. The one female larval brain reconstructed contains roughly 3,000 neurons and 548 thousand chemical synapses. All of these numbers are known to vary between individuals.[8]

Adult brain

Drosophila connectomics started in 1991 with a description of the circuits of the lamina.[9] However the methods used were largely manual and further progress awaited more automated techniques.

In 2011, a high-level connectome, at the level of brain compartments and interconnecting tracts of neurons, for the full fly brain was published,[10] and is available online.[11] New techniques such as digital image processing began to be applied to detailed neural reconstruction.[12]

Reconstructions of larger regions soon followed, including a column of the medulla,[13] also in the visual system of the fruit fly, and the alpha lobe of the mushroom body.[14]

In 2017 a paper introduced an electron microscopy image stack of the whole adult female brain at synaptic resolution. The volume was available for sparse tracing of selected circuits.[15][16]

In 2020, a dense connectome of half the central brain of Drosophila was released,[17] along with a web site that allows queries and exploration of this data.[18] The methods used in reconstruction and initial analysis of the 'hemibrain' connectome followed.[19]

In 2023, using the data from 2017 (above), the full brain connectome (for a female) was published, containing roughly 5x10^7 chemical synapses between ~130,000 neurons.[3] A projectome, a map of projections between regions, can be derived from the connectome. In parallel, a consensus cell type atlas for the Drosophila brain was published, produced based on this 'FlyWire' connectome and the prior 'hemibrain'.[20] This resource includes 4,552 cell types: 3,094 as rigorous validations of those previously proposed in the hemibrain connectome; 1,458 new cell types, arising mostly from the fact that the FlyWire connectome spans the whole brain, whereas the hemibrain derives from a subvolume. Comparison of these distinct, adult Drosophila connectomes showed that cell type counts and strong connections were largely stable, but connection weights were surprisingly variable within and across animals.

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.[21] In 2023, a dense reconstruction of the male fly ventral nerve chord was released.[22]

Larval brain

In 2023, Michael Winding et al. published a complete larval brain connectome.[23][5] This connectome was mapped by annotating the previously collected electron microscopy volume.[24] 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

One of the main uses of the Drosophila connectome is to understand the neural circuits and other brain structure that gives rise to behavior. This area is under very active investigation.[25][26] For example, 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.[27][28]

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.[29][30]

See also

References

  1. ↑ Cachero, Sebastian, Aaron D. Ostrovsky, Y. Yu Jai, Barry J. Dickson, and Gregory SXE Jefferis (2010). "Sexual dimorphism in the fly brain". Current Biology 20 (18): 1589–1601. doi:10.1016/j.cub.2010.07.045. PMID 20832311. PMC 2957842. https://www.cell.com/current-biology/pdf/S0960-9822(10)00947-4.pdf. 
  2. ↑ Kelley, Darcy B.; Bayer, Emily A. (March 22, 2021). "Sexual dimorphism: Neural circuit switches in the Drosophila brain". Current Biology 31 (6): R297–R298. doi:10.1016/j.cub.2021.02.026. PMID 33756143. 
  3. ↑ 3.0 3.1 "CODEX: Connectome Data Explorer". Princeton Neuroscience Institute. https://codex.flywire.ai/. , as described in non-peer-reviewed preprint Dorkenwald S, Matsliah A, Sterling AR, Schlegel P, Yu SC, McKellar CE, et al. (June 2023). "Neuronal wiring diagram of an adult brain". bioRxiv 10.1101/2023.06.27.546656.
  4. ↑ "Analysis tools for Connectomics". Janelia Research Campus, HHMI. https://neuprint.janelia.org/?dataset=manc:v1.0. , as described in non-peer-reviewed preprint Takemura SY, Hayworth KJ, Huang GB, Januszewski M, Lu Z, Marin EC, et al. (June 2023). "A Connectome of the Male Drosophila Ventral Nerve Cord". bioRxiv 10.1101/2023.06.05.543757.
  5. ↑ 5.0 5.1 "The connectome of an insect brain". Science 379 (6636): eadd9330. March 2023. doi:10.1126/science.add9330. PMID 36893230. 
  6. ↑ "The brain activity map project and the challenge of functional connectomics". Neuron 74 (6): 970–974. June 2012. doi:10.1016/j.neuron.2012.06.006. PMID 22726828. 
  7. ↑ "How to map the brain". Nature 571 (7766): S6–S8. July 2019. doi:10.1038/d41586-019-02208-0. PMID 31341309. Bibcode: 2019Natur.571S...6D. 
  8. ↑ Rihani, Karen, and Silke Sachse (2022). "Shedding light on inter-individual variability of olfactory circuits in Drosophila". Frontiers in Behavioral Neuroscience 16 (16): 835680. doi:10.3389/fnbeh.2022.835680. PMID 35548690. 
  9. ↑ "Synaptic organization of columnar elements in the lamina of the wild type in Drosophila melanogaster". The Journal of Comparative Neurology 305 (2): 232–263. March 1991. doi:10.1002/cne.903050206. PMID 1902848. 
  10. ↑ "Three-dimensional reconstruction of brain-wide wiring networks in Drosophila at single-cell resolution". Current Biology 21 (1): 1–11. January 2011. doi:10.1016/j.cub.2010.11.056. PMID 21129968. 
  11. ↑ "FlyCircuit - A Database of Drosophila Brain Neurons". National Center for High-Performance Computing (NCHC). http://flycircuit.tw/. 
  12. ↑ "Wiring economy and volume exclusion determine neuronal placement in the Drosophila brain". Current Biology 21 (23): 2000–2005. December 2011. doi:10.1016/j.cub.2011.10.022. PMID 22119527. 
  13. ↑ "A visual motion detection circuit suggested by Drosophila connectomics". Nature 500 (7461): 175–181. August 2013. doi:10.1038/nature12450. PMID 23925240. Bibcode: 2013Natur.500..175T. 
  14. ↑ "A connectome of a learning and memory center in the adult Drosophila brain". eLife 6: e26975. July 2017. doi:10.7554/eLife.26975. PMID 28718765. 
  15. ↑ "Entire Fruit Fly Brain Imaged with Electron Microscopy" (in en). 31 May 2017. https://www.the-scientist.com/the-scientist/entire-fruit-fly-brain-imaged-with-electron-microscopy-31449. 
  16. ↑ "A Complete Electron Microscopy Volume of the Brain of Adult Drosophila melanogaster". Cell 174 (3): 730–743.e22. July 2018. doi:10.1016/j.cell.2018.06.019. PMID 30033368. 
  17. ↑ Xu CS, Januszewski M, Lu Z, Takemura SY, Hayworth KJ, Huang G, et al. (2020). "A connectome of the adult Drosophila central brain". bioRxiv 10.1101/2020.01.21.911859.
  18. ↑ "Analysis tools for connectomics". Howard Hughes Medical Institute (HHMI). https://neuprint.janelia.org. 
  19. ↑ "A connectome and analysis of the adult Drosophila central brain". eLife 9. September 2020. doi:10.7554/eLife.57443. PMID 32880371. 
  20. ↑ Philipp Schlegel, Yijie Yin, Alexander S. Bates, Sven Dorkenwald, Katharina Eichler, Paul Brooks, Daniel S. Han, Marina Gkantia, Marcia dos Santos, Eva J. Munnelly, Griffin Badalamente, Laia Serratosa Capdevila, Varun A. Sane, Markus W. Pleijzier, Imaan F.M. Tamimi, Christopher R. Dunne, Irene Salgarella, Alexandre Javier, Siqi Fang, Eric Perlman, Tom Kazimiers, Sridhar R. Jagannathan, Arie Matsliah, Amy R. Sterling, Szi-chieh Yu, Claire E. McKellar, FlyWire Consortium, Marta Costa, H. Sebastian Seung, Mala Murthy, Volker Hartenstein, Davi D. Bock, Gregory S.X.E. Jefferis (2023). "Whole-brain annotation and multi-connectome cell typing quantifies circuit stereotypy in Drosophila". pp. 2023–06. bioRxiv 10.1101/2023.06.27.546055.CS1 maint: multiple names: authors list (link)
  21. ↑ "Reconstruction of motor control circuits in adult Drosophila using automated transmission electron microscopy" (in English). Cell 184 (3): 759–774.e18. February 2021. doi:10.1016/j.cell.2020.12.013. PMID 33400916. 
  22. ↑ Takemura, Shin-ya et al. (5 Jun 2023). A Connectome of the Male Drosophila Ventral Nerve Cord. bioRxiv. doi:10.1101/2023.06.05.543757. https://www.biorxiv.org/content/10.1101/2023.06.05.543757v1. 
  23. ↑ "First Complete Map of a Fly Brain Has Uncanny Similarities to AI Neural Networks". 9 March 2023. https://gizmodo.com/first-complete-map-fly-brain-neuroscience-1850206820. 
  24. ↑ "A multilevel multimodal circuit enhances action selection in Drosophila". Nature 520 (7549): 633–639. April 2015. doi:10.1038/nature14297. PMID 25896325. Bibcode: 2015Natur.520..633O. 
  25. ↑ "Kavli Workshop on Neural Circuits and Behavior of Drosophila". Howard Hughes Medical Institute. 2019. https://www.janelia.org/you-janelia/conferences/kavli-workshop-neural-circuits-and-behavior-drosophila. 
  26. ↑ "Crete Workshop on Neural Circuits and Behaviour of Drosophila". Queensland Brain Institute. 2023. https://qbi.uq.edu.au/event/16789/crete-workshop-neural-circuits-and-behaviour-drosophila. 
  27. ↑ "How animals follow their nose" (in en). Knowable Magazine (Annual Reviews). 6 March 2023. doi:10.1146/knowable-030623-4. https://knowablemagazine.org/article/living-world/2023/how-animals-follow-their-nose. Retrieved 13 March 2023. 
  28. ↑ "A neural circuit for wind-guided olfactory navigation". Nature Communications 13 (1): 4613. August 2022. doi:10.1038/s41467-022-32247-7. PMID 35941114. Bibcode: 2022NatCo..13.4613M. 
  29. ↑ "Columbia Workshop on Brain Circuits, Memory and Computation". Center for Neural Engineering and Computation. New York, NY: Columbia University. March 2019. http://www.bionet.ee.columbia.edu/workshops/bcmc/2019. 
  30. ↑ "A connectome is not enough - what is still needed to understand the brain of Drosophila?". The Journal of Experimental Biology 224 (21): jeb242740. November 2021. doi:10.1242/jeb.242740. PMID 34695211. 

Further reading

External links



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