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→Adult brain: Re-order by date to show progress in the field.
→Adult brain: Removed explicit reference to FlyWire. There are several active reconstruction ecosystems (Knossos from Max Planck, Janelia, etc) and this section is about results, not detailed methods.
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}}</ref>. The methods used in reconstruction and initial analysis of the connectome followed.<ref name="Scheffer_2020">{{cite journal | vauthors = Scheffer LK, Xu CS, Januszewski M, Lu Z, Takemura SY, Hayworth KJ, Huang GB, Shinomiya K, Maitlin-Shepard J, Berg S, Clements J, Hubbard PM, Katz WT, Umayam L, Zhao T, Ackerman D, Blakely T, Bogovic J, Dolafi T, Kainmueller D, Kawase T, Khairy KA, Leavitt L, Li PH, Lindsey L, Neubarth N, Olbris DJ, Otsuna H, Trautman ET, Ito M, Bates AS, Goldammer J, Wolff T, Svirskas R, Schlegel P, Neace E, Knecht CJ, Alvarado CX, Bailey DA, Ballinger S, Borycz JA, Canino BS, Cheatham N, Cook M, Dreher M, Duclos O, Eubanks B, Fairbanks K, Finley S, Forknall N, Francis A, Hopkins GP, Joyce EM, Kim S, Kirk NA, Kovalyak J, Lauchie SA, Lohff A, Maldonado C, Manley EA, McLin S, Mooney C, Ndama M, Ogundeyi O, Okeoma N, Ordish C, Padilla N, Patrick CM, Paterson T, Phillips EE, Phillips EM, Rampally N, Ribeiro C, Robertson MK, Rymer JT, Ryan SM, Sammons M, Scott AK, Scott AL, Shinomiya A, Smith C, Smith K, Smith NL, Sobeski MA, Suleiman A, Swift J, Takemura S, Talebi I, Tarnogorska D, Tenshaw E, Tokhi T, Walsh JJ, Yang T, Horne JA, Li F, Parekh R, Rivlin PK, Jayaraman V, Costa M, Jefferis GS, Ito K, Saalfeld S, George R, Meinertzhagen IA, Rubin GM, Hess HF, Jain V, Plaza SM | display-authors = 6 | title = A connectome and analysis of the adult <i>Drosophila</i> central brain | journal = eLife | volume = 9 | issue = | date = September 2020 | pmid = 32880371 | pmc = 7546738 | doi = 10.7554/eLife.57443 }}</ref>
}}</ref>. The methods used in reconstruction and initial analysis of the connectome followed.<ref name="Scheffer_2020">{{cite journal | vauthors = Scheffer LK, Xu CS, Januszewski M, Lu Z, Takemura SY, Hayworth KJ, Huang GB, Shinomiya K, Maitlin-Shepard J, Berg S, Clements J, Hubbard PM, Katz WT, Umayam L, Zhao T, Ackerman D, Blakely T, Bogovic J, Dolafi T, Kainmueller D, Kawase T, Khairy KA, Leavitt L, Li PH, Lindsey L, Neubarth N, Olbris DJ, Otsuna H, Trautman ET, Ito M, Bates AS, Goldammer J, Wolff T, Svirskas R, Schlegel P, Neace E, Knecht CJ, Alvarado CX, Bailey DA, Ballinger S, Borycz JA, Canino BS, Cheatham N, Cook M, Dreher M, Duclos O, Eubanks B, Fairbanks K, Finley S, Forknall N, Francis A, Hopkins GP, Joyce EM, Kim S, Kirk NA, Kovalyak J, Lauchie SA, Lohff A, Maldonado C, Manley EA, McLin S, Mooney C, Ndama M, Ogundeyi O, Okeoma N, Ordish C, Padilla N, Patrick CM, Paterson T, Phillips EE, Phillips EM, Rampally N, Ribeiro C, Robertson MK, Rymer JT, Ryan SM, Sammons M, Scott AK, Scott AL, Shinomiya A, Smith C, Smith K, Smith NL, Sobeski MA, Suleiman A, Swift J, Takemura S, Talebi I, Tarnogorska D, Tenshaw E, Tokhi T, Walsh JJ, Yang T, Horne JA, Li F, Parekh R, Rivlin PK, Jayaraman V, Costa M, Jefferis GS, Ito K, Saalfeld S, George R, Meinertzhagen IA, Rubin GM, Hess HF, Jain V, Plaza SM | display-authors = 6 | title = A connectome and analysis of the adult <i>Drosophila</i> central brain | journal = eLife | volume = 9 | issue = | date = September 2020 | pmid = 32880371 | pmc = 7546738 | doi = 10.7554/eLife.57443 }}</ref>


In 2023, using the data from 2017 (above), the full connectome (for a female) was published: <!-- 127,978 neurons --> "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. [..] <!-- We show how to derive a projectome, a map of projections between regions, from the connectome. We demonstrate the tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine, and descending neurons), across both hemispheres, and between the central brain and the optic lobes. Tracing from a subset of photoreceptors all the way to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviors. --> The technologies and open ecosystem of the FlyWire Consortium set the stage for future large-scale connectome projects in other species."<ref name="Dorkenwald_2023" /> A [[projectome]], a map of projections between regions, can be derived from the connectome.
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<ref name="Dorkenwald_2023" />. A [[projectome]], a map of projections between regions, can be derived from the connectome.


=== Adult ventral nerve cord ===
=== Adult ventral nerve cord ===

Revision as of 13:10, 25 July 2023

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][unreliable source], the male nerve cord[4][unreliable source], 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 looks very good on these counts:

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

Adult brain

Drosophila connectomics started in 1991 with a description of the circuits of the lamina[8]. However the methods used were largely manual and further progress awaited better 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[9], and is available online.[10]. New techniques such as digital image processing began to be applied to connectome reconstruction[11].

Reconstructions of larger regions soon followed, including a column of the medulla[12], also in the visual system of the fruit fly, and the alpha lobe of the mushroom body.[13]

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.[14][15]

In 2020, a dense connectome of half the central brain of Drosophila was released[16], along with a web site that allows queries and exploration of this data[17]. The methods used in reconstruction and initial analysis of the connectome followed.[18]

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.

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.[19] In 2023, a dense reconstruction of the male fly ventral nerve chord was released[20].

Larval brain

In 2023, Michael Winding et al. published a complete larval brain connectome.[21][5] This connectome was mapped by annotating the previously collected electron microscopy volume.[22] 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.[23][24]

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.[25][26]

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" (PDF). Current biology. 20 (18): 1589–1601.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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.
  3. ^ a b 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. ^ 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. ^ a b Winding 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. PMC 7614541. PMID 36893230.
  6. ^ Alivisatos AP, Chun M, Church GM, Greenspan RJ, Roukes ML, Yuste R (June 2012). "The brain activity map project and the challenge of functional connectomics". Neuron. 74 (6): 970–974. doi:10.1016/j.neuron.2012.06.006. PMC 3597383. PMID 22726828.
  7. ^ DeWeerdt S (July 2019). "How to map the brain". Nature. 571 (7766): S6–S8. Bibcode:2019Natur.571S...6D. doi:10.1038/d41586-019-02208-0. PMID 31341309.
  8. ^ 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. PMID 1902848. S2CID 35301798.
  9. ^ Chiang AS, Lin CY, Chuang CC, Chang HM, Hsieh CH, Yeh CW, et al. (January 2011). "Three-dimensional reconstruction of brain-wide wiring networks in Drosophila at single-cell resolution". Current Biology. 21 (1): 1–11. doi:10.1016/j.cub.2010.11.056. PMID 21129968. S2CID 17155338.
  10. ^ "FlyCircuit - A Database of Drosophila Brain Neurons". National Center for High-Performance Computing (NCHC). Retrieved 30 Aug 2013.
  11. ^ Rivera-Alba M, Vitaladevuni SN, Mishchenko Y, Lu Z, Takemura SY, Scheffer L, et al. (December 2011). "Wiring economy and volume exclusion determine neuronal placement in the Drosophila brain". Current Biology. 21 (23): 2000–2005. doi:10.1016/j.cub.2011.10.022. PMC 3244492. PMID 22119527.
  12. ^ Takemura SY, Bharioke A, Lu Z, Nern A, Vitaladevuni S, Rivlin PK, et al. (August 2013). "A visual motion detection circuit suggested by Drosophila connectomics". Nature. 500 (7461): 175–181. Bibcode:2013Natur.500..175T. doi:10.1038/nature12450. PMC 3799980. PMID 23925240.
  13. ^ Takemura SY, Aso Y, Hige T, Wong A, Lu Z, Xu CS, et al. (July 2017). "A connectome of a learning and memory center in the adult Drosophila brain". eLife. 6: e26975. doi:10.7554/eLife.26975. PMC 5550281. PMID 28718765.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  14. ^ Yeager A (31 May 2017). "Entire Fruit Fly Brain Imaged with Electron Microscopy". The Scientist Magazine. Retrieved 2018-07-15.
  15. ^ Zheng Z, Lauritzen JS, Perlman E, Robinson CG, Nichols M, Milkie D, et al. (July 2018). "A Complete Electron Microscopy Volume of the Brain of Adult Drosophila melanogaster". Cell. 174 (3): 730–743.e22. doi:10.1016/j.cell.2018.06.019. PMC 6063995. PMID 30033368.
  16. ^ 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.
  17. ^ "Analysis tools for connectomics". Howard Hughes Medical Institute (HHMI).
  18. ^ Scheffer LK, Xu CS, Januszewski M, Lu Z, Takemura SY, Hayworth KJ, et al. (September 2020). "A connectome and analysis of the adult Drosophila central brain". eLife. 9. doi:10.7554/eLife.57443. PMC 7546738. PMID 32880371.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  19. ^ Phelps JS, Hildebrand DG, Graham BJ, Kuan AT, Thomas LA, Nguyen TM, et al. (February 2021). "Reconstruction of motor control circuits in adult Drosophila using automated transmission electron microscopy". Cell. 184 (3): 759–774.e18. doi:10.1016/j.cell.2020.12.013. PMC 8312698. PMID 33400916.
  20. ^ 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. S2CID 259120564. {{cite journal}}: Cite journal requires |journal= (help)
  21. ^ Leffer L. "First Complete Map of a Fly Brain Has Uncanny Similarities to AI Neural Networks". Gizmodo. Retrieved 10 March 2023.
  22. ^ Ohyama T, Schneider-Mizell CM, Fetter RD, Aleman JV, Franconville R, Rivera-Alba M, et al. (April 2015). "A multilevel multimodal circuit enhances action selection in Drosophila". Nature. 520 (7549): 633–639. doi:10.1038/nature14297. PMID 25896325. S2CID 4464547.
  23. ^ "Columbia Workshop on Brain Circuits, Memory and Computation". Center for Neural Engineering and Computation. New York, NY: Columbia University. March 2019.
  24. ^ 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. PMID 34695211. S2CID 239887246.
  25. ^ Mackenzie D (6 March 2023). "How animals follow their nose". Knowable Magazine. Annual Reviews. doi:10.1146/knowable-030623-4. Retrieved 13 March 2023.
  26. ^ Matheson AM, Lanz AJ, Medina AM, Licata AM, Currier TA, Syed MH, Nagel KI (August 2022). "A neural circuit for wind-guided olfactory navigation". Nature Communications. 13 (1): 4613. doi:10.1038/s41467-022-32247-7. PMC 9360402. PMID 35941114.

Further reading

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