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{{Short description|Connection graph of the brain of the fruit fly Drosophila melanogaster}}
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The '''Drosophila connectome''' is the complete list of connections between [[neuron]]s (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,<ref name="Dorkenwald_2023">{{cite bioRxiv | vauthors = Dorkenwald S, Matsliah A, Sterling AR, Schlegel P, Yu SC, McKellar CE, Lin A, Costa M, Eichler K, Yin Y, Silversmith W, Schneider-Mizell C, Jordan CS, Brittain D, Halageri A, Kuehner K, Ogedengbe O, Morey R, Gager J, Kruk K, Perlman E, Yang R, Deutsch D, Bland D, Sorek M, Lu R, Macrina T, Lee K, Bae JA, Mu S, Nehoran B, Mitchell E, Popovych S, Wu J, Jia Z, Castro M, Kemnitz N, Ih D, Bates AS, Eckstein N, Funke J, Collman F, Bock DD, Jefferis GS, Seung HS, Murthy M | display-authors = 6 | title = Neuronal wiring diagram of an adult brain | date = June 2023 | biorxiv = 10.1101/2023.06.27.546656 }}</ref>{{Unreliable source?|sure=y|reason=Not peer reviewed|date=July 2023}} the male nerve cord,<ref>{{Cite bioRxiv | vauthors = Takemura SY, Hayworth KJ, Huang GB, Januszewski M, Lu Z, Marin EC, Preibisch S, Xu CS, Bogovic J, Champion AS, Cheong HS | date = June 2023 | display-authors = 6 |biorxiv = 10.1101/2023.06.05.543757 |title=A Connectome of the Male Drosophila Ventral Nerve Cord}}</ref>{{Unreliable source?|sure=y|reason=Not peer reviewed|date=July 2023}} and the larval stage.<ref name = "Winding_2023" /> The female fruit fly brain contains 127,978 <!-- 135,000 must be old estimate (for male only?). "~130,000 neurons" for the female, is most recent number for the paper, show it or the precise number from the YouTube video from the researchers? Possibly, and likely the number isn't the same for both sexes, nor the same for each individual of either sex? In some species e.g. C. elegans the number is constant, I doubt for a fly, but I don't know if it's known either way. --> [[neuron]]s (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 <!-- show here adult count, since it for "chemical synapses", is that a synonym synapses, I want to show comparable numbers, if not skip here? --> 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 ''[[Caenorhabditis elegans|C. elegans]]''. The connectomes have been obtained by the methods of [[neural circuit reconstruction]]; <!-- "(EM) brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative, yet inadequate for understanding brain function more globally." A stack of EM images of an entire brain exist, suitable for sparse tracing of specific circuits. --> Many of the 76 compartments of the ''Drosophila'' brain had connectomes available before the publication of the full connectome.
A '''''Drosophila'' connectome''' is a list of [[neuron]]s in the ''[[Drosophila melanogaster]]'' (fruit fly) nervous system, and the chemical [[synapse]]s 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.<ref>{{cite journal |author=Cachero, Sebastian, Aaron D. Ostrovsky, Y. Yu Jai, Barry J. Dickson, and Gregory SXE Jefferis |title=Sexual dimorphism in the fly brain |journal=Current Biology |volume=20 |issue=18 |year=2010 |pages=1589–1601 |doi=10.1016/j.cub.2010.07.045 |pmid=20832311 |pmc=2957842 |s2cid=14207042 |url=https://www.cell.com/current-biology/pdf/S0960-9822(10)00947-4.pdf}}</ref><ref>{{Cite journal |last1=Kelley |first1=Darcy B. |last2=Bayer |first2=Emily A. |date=March 22, 2021 |title=Sexual dimorphism: Neural circuit switches in the Drosophila brain |journal=Current Biology |volume=31 |issue=6 |pages=R297–R298|doi=10.1016/j.cub.2021.02.026 |pmid=33756143 |s2cid=232314832 |doi-access=free }}</ref> Dense connectomes have been completed for the female adult brain,<ref name="Dorkenwald_2023">{{cite web |url=https://codex.flywire.ai/ |title=CODEX: Connectome Data Explorer |publisher=Princeton Neuroscience Institute}},
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as described in non-peer-reviewed preprint {{cite bioRxiv | vauthors = Dorkenwald S, Matsliah A, Sterling AR, Schlegel P, Yu SC, McKellar CE, Lin A, Costa M, Eichler K, Yin Y, Silversmith W, Schneider-Mizell C, Jordan CS, Brittain D, Halageri A, Kuehner K, Ogedengbe O, Morey R, Gager J, Kruk K, Perlman E, Yang R, Deutsch D, Bland D, Sorek M, Lu R, Macrina T, Lee K, Bae JA, Mu S, Nehoran B, Mitchell E, Popovych S, Wu J, Jia Z, Castro M, Kemnitz N, Ih D, Bates AS, Eckstein N, Funke J, Collman F, Bock DD, Jefferis GS, Seung HS, Murthy M | display-authors = 6 | title = Neuronal wiring diagram of an adult brain | date = June 2023 | biorxiv = 10.1101/2023.06.27.546656 }}</ref> the male nerve cord,<ref>{{cite web |url=https://neuprint.janelia.org/?dataset=manc:v1.0 |title=Analysis tools for Connectomics |publisher=Janelia Research Campus, HHMI}}, as described in non-peer-reviewed preprint {{Cite bioRxiv | vauthors = Takemura SY, Hayworth KJ, Huang GB, Januszewski M, Lu Z, Marin EC, Preibisch S, Xu CS, Bogovic J, Champion AS, Cheong HS | date = June 2023 | display-authors = 6 |biorxiv = 10.1101/2023.06.05.543757 |title=A Connectome of the Male Drosophila Ventral Nerve Cord}}</ref> and the female larval stage.<ref name = "Winding_2023" /> The available connectomes show only chemical synapses - other forms of inter-neuron communication such as [[gap junction]]s or [[neuromodulator]]s are not represented. ''Drosophila'' is the most complex creature with a connectome, which had only been previously obtained for three other simpler organisms, first ''[[Caenorhabditis elegans|C. elegans]]''.{{cn|date=June 2024}} 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.{{cn|date=June 2024}} <!-- "(EM) brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative, yet inadequate for understanding brain function more globally." A stack of EM images of an entire brain exist, suitable for sparse tracing of specific circuits. -->


== Why ''Drosophila'' ==
== 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:
[[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,<ref>
* The brain contains about 135,000 neurons,<ref>
{{cite journal | vauthors = Alivisatos AP, Chun M, Church GM, Greenspan RJ, Roukes ML, Yuste R | title = The brain activity map project and the challenge of functional connectomics | journal = Neuron | volume = 74 | issue = 6 | pages = 970–974 | date = June 2012 | pmid = 22726828 | pmc = 3597383 | doi = 10.1016/j.neuron.2012.06.006 }}</ref> small enough to be currently reconstructed .<ref>
{{cite journal | vauthors = Alivisatos AP, Chun M, Church GM, Greenspan RJ, Roukes ML, Yuste R | title = The brain activity map project and the challenge of functional connectomics | journal = Neuron | volume = 74 | issue = 6 | pages = 970–974 | date = June 2012 | pmid = 22726828 | pmc = 3597383 | doi = 10.1016/j.neuron.2012.06.006 }}</ref> small enough to be currently reconstructed.<ref>{{cite journal | vauthors = DeWeerdt S | title = How to map the brain | journal = Nature | volume = 571 | issue = 7766 | pages = S6–S8 | date = July 2019 | pmid = 31341309 | doi = 10.1038/d41586-019-02208-0 | doi-access = free | bibcode = 2019Natur.571S...6D }}</ref>
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* 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.{{cn|date=June 2024}}
{{cite journal | vauthors = DeWeerdt S | title = How to map the brain | journal = Nature | volume = 571 | issue = 7766 | pages = S6–S8 | date = July 2019 | pmid = 31341309 | doi = 10.1038/d41586-019-02208-0 | doi-access = free | bibcode = 2019Natur.571S...6D }}</ref>
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* The [[Drosophila genome|genetics of the fruit fly]] are well understood, and many (tens of thousands) of genetic variants are available.{{clarify | what variants?|date=June 2024}}
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* 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.
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* There are many [[Electrophysiology|electrophysiological]], [[calcium imaging]], and other studies ongoing with ''Drosophila''.{{cn|date=June 2024}}
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* The [[Drosophila genome|genetics of the fruit fly]] are well understood, and many (tens of thousands) of genetic variants are available.
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* There are many electrophysiological, [[calcium imaging]], and other studies ongoing with ''Drosophila''.


== Structure of the fly connectome ==
== 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 [[descending neuron|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.<ref>{{cite journal |author=Rihani, Karen, and Silke Sachse |title=Shedding light on inter-individual variability of olfactory circuits in Drosophila |journal= Frontiers in Behavioral Neuroscience |issue=16 |year=2022 |volume=16 |pages=835680|doi=10.3389/fnbeh.2022.835680 |pmid=35548690 |pmc=9084309 |doi-access=free }}</ref>


=== Adult brain ===
=== Adult brain ===
''Drosophila'' connectomics started in 1991 with a description of the circuits of the [[Lamina (neuropil)|lamina]].<ref>
In 2023, 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.
{{cite journal | vauthors = [[Ian Meinertzhagen|Meinertzhagen IA]], O'Neil SD | title = Synaptic organization of columnar elements in the lamina of the wild type in Drosophila melanogaster | journal = The Journal of Comparative Neurology | volume = 305 | issue = 2 | pages = 232–263 | date = March 1991 | pmid = 1902848 | doi = 10.1002/cne.903050206 | s2cid = 35301798 }}</ref> However the methods used were largely manual and further progress awaited more automated techniques.


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.<ref>
In 2011, a high-level connectome, at the level of brain compartments and interconnecting tracts of neurons, for the full fly brain was published,<ref>
{{cite journal | vauthors = Chiang AS, Lin CY, Chuang CC, Chang HM, Hsieh CH, Yeh CW, Shih CT, Wu JJ, Wang GT, Chen YC, Wu CC, Chen GY, Ching YT, Lee PC, Lin CY, Lin HH, Wu CC, Hsu HW, Huang YA, Chen JY, Chiang HJ, Lu CF, Ni RF, Yeh CY, Hwang JK | display-authors = 6 | title = Three-dimensional reconstruction of brain-wide wiring networks in Drosophila at single-cell resolution | journal = Current Biology | volume = 21 | issue = 1 | pages = 1–11 | date = January 2011 | pmid = 21129968 | doi = 10.1016/j.cub.2010.11.056 | s2cid = 17155338 | doi-access = free }}</ref> A version of this is available online.<ref>{{cite web |title=FlyCircuit - A Database of ''Drosophila'' Brain Neurons |url=http://flycircuit.tw/ | work = National Center for High-Performance Computing (NCHC) | access-date=30 Aug 2013 }}</ref>
{{cite journal | vauthors = Chiang AS, Lin CY, Chuang CC, Chang HM, Hsieh CH, Yeh CW, Shih CT, Wu JJ, Wang GT, Chen YC, Wu CC, Chen GY, Ching YT, Lee PC, Lin CY, Lin HH, Wu CC, Hsu HW, Huang YA, Chen JY, Chiang HJ, Lu CF, Ni RF, Yeh CY, Hwang JK | display-authors = 6 | title = Three-dimensional reconstruction of brain-wide wiring networks in Drosophila at single-cell resolution | journal = Current Biology | volume = 21 | issue = 1 | pages = 1–11 | date = January 2011 | pmid = 21129968 | doi = 10.1016/j.cub.2010.11.056 | s2cid = 17155338 | doi-access = free }}</ref> and is available online.<ref>{{cite web |title=FlyCircuit - A Database of ''Drosophila'' Brain Neurons |url=http://flycircuit.tw/ | work = National Center for High-Performance Computing (NCHC) | access-date=30 Aug 2013 }}</ref> New techniques such as digital image processing began to be applied to detailed neural reconstruction.<ref>{{cite journal | vauthors = Rivera-Alba M, Vitaladevuni SN, Mishchenko Y, Lu Z, Takemura SY, Scheffer L, Meinertzhagen IA, Chklovskii DB, de Polavieja GG | display-authors = 6 | title = Wiring economy and volume exclusion determine neuronal placement in the Drosophila brain | journal = Current Biology | volume = 21 | issue = 23 | pages = 2000–2005 | date = December 2011 | pmid = 22119527 | pmc = 3244492 | doi = 10.1016/j.cub.2011.10.022 }}</ref>


Reconstructions of larger regions soon followed, including a column of the [[Optic lobe (arthropods)|medulla]],<ref>
Detailed circuit-level connectomes exist for the [[Lamina (neuropil)|lamina]]<ref>
{{cite journal | vauthors = Meinertzhagen IA, O'Neil SD | title = Synaptic organization of columnar elements in the lamina of the wild type in Drosophila melanogaster | journal = The Journal of Comparative Neurology | volume = 305 | issue = 2 | pages = 232–263 | date = March 1991 | pmid = 1902848 | doi = 10.1002/cne.903050206 | s2cid = 35301798 }}</ref><ref>
{{cite journal | vauthors = Takemura SY, Bharioke A, Lu Z, Nern A, Vitaladevuni S, Rivlin PK, Katz WT, Olbris DJ, Plaza SM, Winston P, Zhao T, Horne JA, Fetter RD, Takemura S, Blazek K, Chang LA, Ogundeyi O, Saunders MA, Shapiro V, Sigmund C, Rubin GM, Scheffer LK, Meinertzhagen IA, Chklovskii DB | display-authors = 6 | title = A visual motion detection circuit suggested by Drosophila connectomics | journal = Nature | volume = 500 | issue = 7461 | pages = 175–181 | date = August 2013 | pmid = 23925240 | pmc = 3799980 | doi = 10.1038/nature12450 | bibcode = 2013Natur.500..175T }}</ref> also in the visual system of the fruit fly, and the alpha lobe of the mushroom body.<ref>
{{cite journal | vauthors = Rivera-Alba M, Vitaladevuni SN, Mishchenko Y, Lu Z, Takemura SY, Scheffer L, Meinertzhagen IA, Chklovskii DB, de Polavieja GG | display-authors = 6 | title = Wiring economy and volume exclusion determine neuronal placement in the Drosophila brain | journal = Current Biology | volume = 21 | issue = 23 | pages = 2000–2005 | date = December 2011 | pmid = 22119527 | pmc = 3244492 | doi = 10.1016/j.cub.2011.10.022 }}</ref> and a [[Optic lobe (arthropods)|medulla]]<ref>
{{cite journal | vauthors = Takemura SY, Aso Y, Hige T, Wong A, Lu Z, Xu CS, Rivlin PK, Hess H, Zhao T, Parag T, Berg S, Huang G, Katz W, Olbris DJ, Plaza S, Umayam L, Aniceto R, Chang LA, Lauchie S, Ogundeyi O, Ordish C, Shinomiya A, Sigmund C, Takemura S, Tran J, Turner GC, Rubin GM, Scheffer LK | display-authors = 6 | title = A connectome of a learning and memory center in the adult ''Drosophila'' brain | journal = eLife | volume = 6 | pages = e26975 | date = July 2017 | pmid = 28718765 | pmc = 5550281 | doi = 10.7554/eLife.26975 | doi-access = free }}</ref>
{{cite journal | vauthors = Takemura SY, Bharioke A, Lu Z, Nern A, Vitaladevuni S, Rivlin PK, Katz WT, Olbris DJ, Plaza SM, Winston P, Zhao T, Horne JA, Fetter RD, Takemura S, Blazek K, Chang LA, Ogundeyi O, Saunders MA, Shapiro V, Sigmund C, Rubin GM, Scheffer LK, Meinertzhagen IA, Chklovskii DB | display-authors = 6 | title = A visual motion detection circuit suggested by Drosophila connectomics | journal = Nature | volume = 500 | issue = 7461 | pages = 175–181 | date = August 2013 | pmid = 23925240 | pmc = 3799980 | doi = 10.1038/nature12450 | bibcode = 2013Natur.500..175T }}</ref> column, both in the visual system of the fruit fly, and the alpha lobe of the mushroom body.<ref>
{{cite journal | vauthors = Takemura SY, Aso Y, Hige T, Wong A, Lu Z, Xu CS, Rivlin PK, Hess H, Zhao T, Parag T, Berg S, Huang G, Katz W, Olbris DJ, Plaza S, Umayam L, Aniceto R, Chang LA, Lauchie S, Ogundeyi O, Ordish C, Shinomiya A, Sigmund C, Takemura S, Tran J, Turner GC, Rubin GM, Scheffer LK | display-authors = 6 | title = A connectome of a learning and memory center in the adult <i>Drosophila</i> brain | journal = eLife | volume = 6 | pages = e26975 | date = July 2017 | pmid = 28718765 | pmc = 5550281 | doi = 10.7554/eLife.26975 }}</ref>


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.<ref>{{Cite web | vauthors = Yeager A |date=31 May 2017 |url=https://www.the-scientist.com/the-scientist/entire-fruit-fly-brain-imaged-with-electron-microscopy-31449 |title=Entire Fruit Fly Brain Imaged with Electron Microscopy |website=The Scientist Magazine |language=en |access-date=2018-07-15 }}</ref><ref name="Zheng_2018">{{cite journal | vauthors = Zheng Z, Lauritzen JS, Perlman E, Robinson CG, Nichols M, Milkie D, Torrens O, Price J, Fisher CB, Sharifi N, Calle-Schuler SA, Kmecova L, Ali IJ, Karsh B, Trautman ET, Bogovic JA, Hanslovsky P, Jefferis GS, Kazhdan M, Khairy K, Saalfeld S, Fetter RD, Bock DD | display-authors = 6 | title = A Complete Electron Microscopy Volume of the Brain of Adult Drosophila melanogaster | journal = Cell | volume = 174 | issue = 3 | pages = 730–743.e22 | date = July 2018 | pmid = 30033368 | pmc = 6063995 | doi = 10.1016/j.cell.2018.06.019 }}</ref>
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.<ref>{{Cite web | vauthors = Yeager A |date=31 May 2017 |url=https://www.the-scientist.com/the-scientist/entire-fruit-fly-brain-imaged-with-electron-microscopy-31449 |title=Entire Fruit Fly Brain Imaged with Electron Microscopy |website=The Scientist Magazine |language=en |access-date=2018-07-15 }}</ref><ref name="Zheng_2018">{{cite journal | vauthors = Zheng Z, Lauritzen JS, Perlman E, Robinson CG, Nichols M, Milkie D, Torrens O, Price J, Fisher CB, Sharifi N, Calle-Schuler SA, Kmecova L, Ali IJ, Karsh B, Trautman ET, Bogovic JA, Hanslovsky P, Jefferis GS, Kazhdan M, Khairy K, Saalfeld S, Fetter RD, Bock DD | display-authors = 6 | title = A Complete Electron Microscopy Volume of the Brain of Adult Drosophila melanogaster | journal = Cell | volume = 174 | issue = 3 | pages = 730–743.e22 | date = July 2018 | pmid = 30033368 | pmc = 6063995 | doi = 10.1016/j.cell.2018.06.019 }}</ref>


In 2020, a dense connectome of half the central brain of ''Drosophila'' was released,<ref>{{cite bioRxiv | vauthors = Xu CS, Januszewski M, Lu Z, Takemura SY, Hayworth KJ, Huang G, Shinomiya K, Maitin-Shepard J, Ackerman D, Berg S, Blakely T |display-authors=6 |year=2020 |title=A connectome of the adult ''Drosophila'' central brain |biorxiv=10.1101/2020.01.21.911859 }}</ref> along with a web site that allows queries and exploration of this data.<ref>{{cite web |title=Analysis tools for connectomics |url=https://neuprint.janelia.org |publisher=Howard Hughes Medical Institute (HHMI)
In 2020, a dense connectome of half the central brain of ''Drosophila'' was released,<ref>{{cite bioRxiv | vauthors = Xu CS, Januszewski M, Lu Z, Takemura SY, Hayworth KJ, Huang G, Shinomiya K, Maitin-Shepard J, Ackerman D, Berg S, Blakely T |display-authors=6 |year=2020 |title=A connectome of the adult ''Drosophila'' central brain |biorxiv=10.1101/2020.01.21.911859 }}</ref> along with a web site that allows queries and exploration of this data.<ref>{{cite web |title=Analysis tools for connectomics |url=https://neuprint.janelia.org |publisher=Howard Hughes Medical Institute (HHMI)
}}</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 'hemibrain' 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 ''Drosophila'' central brain | journal = eLife | volume = 9 | issue = | date = September 2020 | pmid = 32880371 | pmc = 7546738 | doi = 10.7554/eLife.57443 | doi-access = free }}</ref>

In 2023, using the data from 2017 (above), the full brain connectome (for a female) was made available, 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. In parallel, a consensus [[cell type]] atlas for the ''Drosophila'' brain was published, produced based on this 'FlyWire' connectome and the prior 'hemibrain'.<ref>{{cite bioRxiv
|biorxiv=10.1101/2023.06.27.546055 |author=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 |title=Whole-brain annotation and multi-connectome cell typing quantifies circuit stereotypy in Drosophila |year=2023 |pages=2023–06 }}</ref> 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 ===
=== 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.<ref>{{cite journal | vauthors = Phelps JS, Hildebrand DG, Graham BJ, Kuan AT, Thomas LA, Nguyen TM, Buhmann J, Azevedo AW, Sustar A, Agrawal S, Liu M, Shanny BL, Funke J, Tuthill JC, Lee WA | display-authors = 6 | title = Reconstruction of motor control circuits in adult Drosophila using automated transmission electron microscopy | language = English | journal = Cell | volume = 184 | issue = 3 | pages = 759–774.e18 | date = February 2021 | pmid = 33400916 | pmc = 8312698 | doi = 10.1016/j.cell.2020.12.013 }}</ref> In 2023, a dense reconstruction of the male fly ventral nerve chord was released<ref>{{cite journal |url=https://www.biorxiv.org/content/10.1101/2023.06.05.543757v1 |title=A Connectome of the Male Drosophila Ventral Nerve Cord |date=5 Jun 2023 |publisher=bioRxiv|doi=10.1101/2023.06.05.543757 |last1=Takemura |first1=Shin-ya |last2=Hayworth |first2=Kenneth J. |last3=Huang |first3=Gary B. |last4=Januszewski |first4=Michal |last5=Lu |first5=Zhiyuan |last6=Marin |first6=Elizabeth C. |last7=Preibisch |first7=Stephan |last8=Xu |first8=C Shan |last9=Bogovic |first9=John |last10=Champion |first10=Andrew S. |last11=Cheong |first11=Han SJ |last12=Costa |first12=Marta |last13=Eichler |first13=Katharina |last14=Katz |first14=William |last15=Knecht |first15=Christopher |last16=Li |first16=Feng |last17=Morris |first17=Billy J. |last18=Ordish |first18=Christopher |last19=Rivlin |first19=Patricia K. |last20=Schlegel |first20=Philipp |last21=Shinomiya |first21=Kazunori |last22=Stürner |first22=Tomke |last23=Zhao |first23=Ting |last24=Badalamente |first24=Griffin |last25=Bailey |first25=Dennis |last26=Brooks |first26=Paul |last27=Canino |first27=Brandon S. |last28=Clements |first28=Jody |last29=Cook |first29=Michael |last30=Duclos |first30=Octave |s2cid=259120564 |display-authors=1 }}</ref>.
In 2022, a group of scientists mapped the motor control circuits of the ventral nerve cord of a female fruit fly using electron microscopy.<ref>{{cite journal | vauthors = Phelps JS, Hildebrand DG, Graham BJ, Kuan AT, Thomas LA, Nguyen TM, Buhmann J, Azevedo AW, Sustar A, Agrawal S, Liu M, Shanny BL, Funke J, Tuthill JC, Lee WA | display-authors = 6 | title = Reconstruction of motor control circuits in adult Drosophila using automated transmission electron microscopy | language = English | journal = Cell | volume = 184 | issue = 3 | pages = 759–774.e18 | date = February 2021 | pmid = 33400916 | pmc = 8312698 | doi = 10.1016/j.cell.2020.12.013 }}</ref> In 2023, a dense reconstruction of the male fly ventral nerve chord was released.<ref>{{cite journal |url=https://www.biorxiv.org/content/10.1101/2023.06.05.543757v1 |title=A Connectome of the Male Drosophila Ventral Nerve Cord |date=5 Jun 2023 |publisher=bioRxiv|doi=10.1101/2023.06.05.543757 |last1=Takemura |first1=Shin-ya |last2=Hayworth |first2=Kenneth J. |last3=Huang |first3=Gary B. |last4=Januszewski |first4=Michal |last5=Lu |first5=Zhiyuan |last6=Marin |first6=Elizabeth C. |last7=Preibisch |first7=Stephan |last8=Xu |first8=C Shan |last9=Bogovic |first9=John |last10=Champion |first10=Andrew S. |last11=Cheong |first11=Han SJ |last12=Costa |first12=Marta |last13=Eichler |first13=Katharina |last14=Katz |first14=William |last15=Knecht |first15=Christopher |last16=Li |first16=Feng |last17=Morris |first17=Billy J. |last18=Ordish |first18=Christopher |last19=Rivlin |first19=Patricia K. |last20=Schlegel |first20=Philipp |last21=Shinomiya |first21=Kazunori |last22=Stürner |first22=Tomke |last23=Zhao |first23=Ting |last24=Badalamente |first24=Griffin |last25=Bailey |first25=Dennis |last26=Brooks |first26=Paul |last27=Canino |first27=Brandon S. |last28=Clements |first28=Jody |last29=Cook |first29=Michael |last30=Duclos |first30=Octave |s2cid=259120564 |display-authors=1 }}</ref>


=== Larval brain ===
=== Larval brain ===
In 2023, Michael Winding et al. published a complete larval brain connectome.<ref>{{cite web | vauthors = Leffer L |title=First Complete Map of a Fly Brain Has Uncanny Similarities to AI Neural Networks |url=https://gizmodo.com/first-complete-map-fly-brain-neuroscience-1850206820 |access-date=10 March 2023 |website=Gizmodo}}</ref><ref name = "Winding_2023">{{cite journal | vauthors = Winding M, Pedigo BD, Barnes CL, Patsolic HG, Park Y, Kazimiers T, Fushiki A, Andrade IV, Khandelwal A, Valdes-Aleman J, Li F, Randel N, Barsotti E, Correia A, Fetter RD, Hartenstein V, Priebe CE, Vogelstein JT, Cardona A, Zlatic M | display-authors = 6 | title = The connectome of an insect brain | journal = Science | volume = 379 | issue = 6636 | pages = eadd9330 | date = March 2023 | pmid = 36893230 | doi = 10.1126/science.add9330 | pmc = 7614541 }}</ref> This connectome was mapped by annotating the previously collected electron microscopy volume.<ref>{{cite journal | vauthors = Ohyama T, Schneider-Mizell CM, Fetter RD, Aleman JV, Franconville R, Rivera-Alba M, Mensh BD, Branson KM, Simpson JH, Truman JW, Cardona A, Zlatic M | display-authors = 6 | title = A multilevel multimodal circuit enhances action selection in Drosophila | journal = Nature | volume = 520 | issue = 7549 | pages = 633–639 | date = April 2015 | pmid = 25896325 | doi = 10.1038/nature14297 | s2cid = 4464547 }}</ref> 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.
In 2023, Michael Winding et al. published a complete larval brain connectome.<ref>{{cite web | vauthors = Leffer L |title=First Complete Map of a Fly Brain Has Uncanny Similarities to AI Neural Networks |url=https://gizmodo.com/first-complete-map-fly-brain-neuroscience-1850206820 |access-date=10 March 2023 |website=Gizmodo|date=9 March 2023 }}</ref><ref name = "Winding_2023">{{cite journal | vauthors = Winding M, Pedigo BD, Barnes CL, Patsolic HG, Park Y, Kazimiers T, Fushiki A, Andrade IV, Khandelwal A, Valdes-Aleman J, Li F, Randel N, Barsotti E, Correia A, Fetter RD, Hartenstein V, Priebe CE, Vogelstein JT, Cardona A, Zlatic M | display-authors = 6 | title = The connectome of an insect brain | journal = Science | volume = 379 | issue = 6636 | pages = eadd9330 | date = March 2023 | pmid = 36893230 | doi = 10.1126/science.add9330 | pmc = 7614541 }}</ref> This connectome was mapped by annotating the previously collected electron microscopy volume.<ref>{{cite journal | vauthors = Ohyama T, Schneider-Mizell CM, Fetter RD, Aleman JV, Franconville R, Rivera-Alba M, Mensh BD, Branson KM, Simpson JH, Truman JW, Cardona A, Zlatic M | display-authors = 6 | title = A multilevel multimodal circuit enhances action selection in Drosophila | journal = Nature | volume = 520 | issue = 7549 | pages = 633–639 | date = April 2015 | pmid = 25896325 | doi = 10.1038/nature14297 | bibcode = 2015Natur.520..633O | s2cid = 4464547 }}</ref> 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 neuron|sensory neurons]] (visual, olfactory, gustatory, thermal, etc), [[Descending neuron|descending neurons]], and [[ascending neurons]].
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 neuron]]s (visual, olfactory, gustatory, thermal, etc), [[descending neuron]]s, 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.
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 ==
== 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.<ref>{{cite web |title=Kavli Workshop on Neural Circuits and Behavior of Drosophila |url=https://www.janelia.org/you-janelia/conferences/kavli-workshop-neural-circuits-and-behavior-drosophila |date=2019 |publisher=Howard Hughes Medical Institute}}</ref><ref>{{cite web |title=Crete Workshop on Neural Circuits and Behaviour of Drosophila |url=https://qbi.uq.edu.au/event/16789/crete-workshop-neural-circuits-and-behaviour-drosophila |year=2023 |publisher=Queensland Brain Institute}}</ref> 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.<ref name="Mackenzie_2023">{{cite journal | vauthors = Mackenzie D |title=How animals follow their nose |journal=Knowable Magazine |publisher=Annual Reviews |date=6 March 2023 |doi=10.1146/knowable-030623-4 |doi-access=free |url=https://knowablemagazine.org/article/living-world/2023/how-animals-follow-their-nose |access-date=13 March 2023 |language=en}}</ref><ref name="Matheson_2022">{{cite journal | vauthors = Matheson AM, Lanz AJ, Medina AM, Licata AM, Currier TA, Syed MH, Nagel KI | title = A neural circuit for wind-guided olfactory navigation | journal = Nature Communications | volume = 13 | issue = 1 | pages = 4613 | date = August 2022 | pmid = 35941114 | doi = 10.1038/s41467-022-32247-7 | pmc = 9360402 | bibcode = 2022NatCo..13.4613M }}</ref>
⚫
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 (biochemistry) | receptor]] types and locations, [[neuromodulators]] and [[hormones]] (with sources and receptors), the role of [[glial cells]], [[Synapse#Role_in_memory | time evolution rules]] for synapses, and more.<ref>{{cite web |url= http://www.bionet.ee.columbia.edu/workshops/bcmc/2019 | title = Columbia Workshop on Brain Circuits, Memory and Computation | work = Center for Neural Engineering and Computation | publisher = Columbia University | location = New York, NY | date = March 2019 }}</ref><ref>{{cite journal | vauthors = Scheffer LK, Meinertzhagen IA | title = A connectome is not enough - what is still needed to understand the brain of Drosophila? | journal = The Journal of Experimental Biology | volume = 224 | issue = 21 | pages = jeb242740 | date = November 2021 | pmid = 34695211 | doi = 10.1242/jeb.242740 | s2cid = 239887246 }}</ref>


⚫
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 (biochemistry)|receptor]] types and locations, [[neuromodulators]] and [[hormones]] (with sources and receptors), the role of [[glial cells]], [[Synapse#Role in memory|time evolution rules]] for synapses, and more.<ref>{{cite web |url= http://www.bionet.ee.columbia.edu/workshops/bcmc/2019 | title = Columbia Workshop on Brain Circuits, Memory and Computation | work = Center for Neural Engineering and Computation | publisher = Columbia University | location = New York, NY | date = March 2019 }}</ref><ref>{{cite journal | vauthors = Scheffer LK, Meinertzhagen IA | title = A connectome is not enough - what is still needed to understand the brain of Drosophila? | journal = The Journal of Experimental Biology | volume = 224 | issue = 21 | pages = jeb242740 | date = November 2021 | pmid = 34695211 | doi = 10.1242/jeb.242740 | s2cid = 239887246 | doi-access = free }}</ref>
⚫
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.<ref name="Mackenzie_2023">{{cite journal | vauthors = Mackenzie D |title=How animals follow their nose |journal=Knowable Magazine |publisher=Annual Reviews |date=6 March 2023 |doi=10.1146/knowable-030623-4 |doi-access=free |url=https://knowablemagazine.org/article/living-world/2023/how-animals-follow-their-nose |access-date=13 March 2023 |language=en}}</ref><ref name="Matheson_2022">{{cite journal | vauthors = Matheson AM, Lanz AJ, Medina AM, Licata AM, Currier TA, Syed MH, Nagel KI | title = A neural circuit for wind-guided olfactory navigation | journal = Nature Communications | volume = 13 | issue = 1 | pages = 4613 | date = August 2022 | pmid = 35941114 | doi = 10.1038/s41467-022-32247-7 | pmc = 9360402 }}</ref>


== See also ==
== See also ==
Line 65: Line 69:


[[Category:Brain]]
[[Category:Brain]]
[[Category:Emerging technologies]]
[[Category:Neural coding]]
[[Category:Neural coding]]
[[Category:Neuroimaging]]
[[Category:Neuroimaging]]

Latest revision as of 19:06, 16 September 2024

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.[citation needed] 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.[citation needed]

Why Drosophila

[edit]

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:

Structure of the fly connectome

[edit]

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

[edit]

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 made available, 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

[edit]

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

[edit]

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

[edit]

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

[edit]

References

[edit]
  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. doi:10.1016/j.cub.2010.07.045. PMC 2957842. PMID 20832311. S2CID 14207042.{{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. doi:10.1016/j.cub.2021.02.026. PMID 33756143. S2CID 232314832.
  3. ^ a b "CODEX: Connectome Data Explorer". Princeton Neuroscience Institute., 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., 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. ^ 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. ^ 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. PMC 9084309. PMID 35548690.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ 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.
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Further reading

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