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9 results on '"Chelsea X Alvarado"'

1. A connectome and analysis of the adult Drosophila central brain

Author

Louis K Scheffer, C Shan Xu, Michal Januszewski, Zhiyuan Lu, Shin-ya Takemura, Kenneth J Hayworth, Gary B Huang, Kazunori Shinomiya, Jeremy Maitlin-Shepard, Stuart Berg, Jody Clements, Philip M Hubbard, William T Katz, Lowell Umayam, Ting Zhao, David Ackerman, Tim Blakely, John Bogovic, Tom Dolafi, Dagmar Kainmueller, Takashi Kawase, Khaled A Khairy, Laramie Leavitt, Peter H Li, Larry Lindsey, Nicole Neubarth, Donald J Olbris, Hideo Otsuna, Eric T Trautman, Masayoshi Ito, Alexander S Bates, Jens Goldammer, Tanya Wolff, Robert Svirskas, Philipp Schlegel, Erika Neace, Christopher J Knecht, Chelsea X Alvarado, Dennis A Bailey, Samantha Ballinger, Jolanta A Borycz, Brandon S Canino, Natasha Cheatham, Michael Cook, Marisa Dreher, Octave Duclos, Bryon Eubanks, Kelli Fairbanks, Samantha Finley, Nora Forknall, Audrey Francis, Gary Patrick Hopkins, Emily M Joyce, SungJin Kim, Nicole A Kirk, Julie Kovalyak, Shirley A Lauchie, Alanna Lohff, Charli Maldonado, Emily A Manley, Sari McLin, Caroline Mooney, Miatta Ndama, Omotara Ogundeyi, Nneoma Okeoma, Christopher Ordish, Nicholas Padilla, Christopher M Patrick, Tyler Paterson, Elliott E Phillips, Emily M Phillips, Neha Rampally, Caitlin Ribeiro, Madelaine K Robertson, Jon Thomson Rymer, Sean M Ryan, Megan Sammons, Anne K Scott, Ashley L Scott, Aya Shinomiya, Claire Smith, Kelsey Smith, Natalie L Smith, Margaret A Sobeski, Alia Suleiman, Jackie Swift, Satoko Takemura, Iris Talebi, Dorota Tarnogorska, Emily Tenshaw, Temour Tokhi, John J Walsh, Tansy Yang, Jane Anne Horne, Feng Li, Ruchi Parekh, Patricia K Rivlin, Vivek Jayaraman, Marta Costa, Gregory SXE Jefferis, Kei Ito, Stephan Saalfeld, Reed George, Ian A Meinertzhagen, Gerald M Rubin, Harald F Hess, Viren Jain, and Stephen M Plaza

Subjects
connectome, brain regions, cell types, graph properties, connectome reconstuction methods, synapse detecton, Medicine, Science, Biology (General), QH301-705.5
Abstract

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly’s brain.

Published
2020
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2. Lack of genetic evidence for NLRP3 inflammasome involvement in Parkinson’s disease pathogenesis

Author

Konstantin Senkevich, Lang Liu, Chelsea X. Alvarado, Hampton L. Leonard, Mike A. Nalls, Global Parkinson’s Genetics Program (GP2), and Ziv Gan-Or

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Activation of the NLRP3 inflammasome has been implicated in Parkinson’s disease (PD) based on in vitro and in vivo studies. Clinical trials targeting the NLRP3 inflammasome in PD are ongoing. However, the evidence supporting NLRP3’s involvement in PD from human genetics data is limited. We analyzed common and rare variants in NLRP3 inflammasome-related genes in PD cohorts, performed pathway-specific polygenic risk score (PRS) analyses, and studied causal associations using Mendelian randomization (MR) with the NLRP3 components and the cytokines IL-1β and IL-18. Our findings showed no associations of common or rare variants, nor of the pathway PRS with PD. MR suggests that altering the expression of the NLRP3 inflammasome, IL-1β, or IL-18, does not affect PD risk or progression. Therefore, our results do not support a role for the NLRP3 inflammasome in PD pathogenesis or as a target for drug development.

Published
2024
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3. Exploring the genetic and genomic connection underlying neurodegeneration with brain iron accumulation and the risk for Parkinson’s disease

Author

Pilar Alvarez Jerez, Jose Luis Alcantud, Lucia de los Reyes-Ramírez, Anni Moore, Clara Ruz, Francisco Vives Montero, Noela Rodriguez-Losada, Prabhjyot Saini, Ziv Gan-Or, Chelsea X. Alvarado, Mary B. Makarious, Kimberley J. Billingsley, Cornelis Blauwendraat, Alastair J. Noyce, Andrew B. Singleton, Raquel Duran, and Sara Bandres-Ciga

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Neurodegeneration with brain iron accumulation (NBIA) represents a group of neurodegenerative disorders characterized by abnormal iron accumulation in the brain. In Parkinson’s Disease (PD), iron accumulation is a cardinal feature of degenerating regions in the brain and seems to be a key player in mechanisms that precipitate cell death. The aim of this study was to explore the genetic and genomic connection between NBIA and PD. We screened for known and rare pathogenic mutations in autosomal dominant and recessive genes linked to NBIA in a total of 4481 PD cases and 10,253 controls from the Accelerating Medicines Partnership Parkinsons’ Disease Program and the UKBiobank. We examined whether a genetic burden of NBIA variants contributes to PD risk through single-gene, gene-set, and single-variant association analyses. In addition, we assessed publicly available expression quantitative trait loci (eQTL) data through Summary-based Mendelian Randomization and conducted transcriptomic analyses in blood of 1886 PD cases and 1285 controls. Out of 29 previously reported NBIA screened coding variants, four were associated with PD risk at a nominal p value

Published
2023
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4. omicSynth: an Open Multi-omic Community Resource for Identifying Druggable Targets across Neurodegenerative Diseases

Author

Chelsea X. Alvarado, Mary B. Makarious, Dan Vitale, Mathew J. Koretsky, Sara Bandres-Ciga, Hirotaka Iwaki, Kristin Levine, Andrew Singleton, Faraz Faghri, Mike A. Nalls, and Hampton L. Leonard

Subjects
Article
Abstract

Treatments for neurodegenerative disorders remain rare, although recent FDA approvals, such as Lecanemab and Aducanumab for Alzheimer’s Disease, highlight the importance of a mechanistic approach in creating disease modifying therapies. As a large portion of the global population is aging, there is an urgent need for therapeutics that can stop disease progression and eliminate symptoms. In this study, we create an open framework and resource for evidence based identification of therapeutic targets for neurodegenerative disease. We use Summary-data-based Mendelian Randomization to identify genetic targets for drug discovery and repurposing. In parallel, we provide mechanistic insights into disease processes and potential network-level consequences of gene-based therapeutics. We identified 116 Alzheimer’s disease, 3 amyotrophic lateral sclerosis, 5 Lewy body dementia, 46 Parkinson’s disease, and 9 Progressive supranuclear palsy target genes passing multiple test corrections (pSMR_multi< 2.95E-06 and pHEIDI> 0.01). We created a therapeutic scheme to classify our identified target genes into strata based on druggability and approved therapeutics - classifying 41noveltargets, 3knowntargets, and 115difficulttargets. Ournovelclass of genes provides a springboard for new opportunities in drug discovery, development and repurposing in the pre-competitive space. We also provide a user-friendly web platform to help users explore potential therapeutic targets for neurodegenerative diseases, decreasing activation energy for the community [https://nih-card-ndd-smr-home-syboky.streamlit.app/].

Published
2023

5. Multi-ancestry meta-analysis and fine-mapping in Alzheimer’s Disease

Author

Julie Lake, Caroline Warly Solsberg, Jonggeol Jeffrey Kim, Juliana Acosta-Uribe, Mary B. Makarious, Zizheng Li, Kristin Levine, Peter Heutink, Chelsea X. Alvarado, Dan Vitale, Sarang Kang, Jungsoo Gim, Kun Ho Lee, Stefanie D. Pina-Escudero, Luigi Ferrucci, Andrew B. Singleton, Cornelis Blauwendraat, Mike A. Nalls, Jennifer S. Yokoyama, and Hampton L. Leonard

Subjects
Cellular and Molecular Neuroscience, Psychiatry and Mental health, Molecular Biology
Abstract

Genome-wide association studies (GWAS) of Alzheimer’s disease are predominantly carried out in European ancestry individuals despite the known variation in genetic architecture and disease prevalence across global populations. We leveraged published GWAS summary statistics from European, East Asian, and African American populations, and an additional GWAS from a Caribbean Hispanic population using previously reported genotype data to perform the largest multi-ancestry GWAS meta-analysis of Alzheimer’s disease and related dementias to date. This method allowed us to identify two independent novel disease-associated loci on chromosome 3. We also leveraged diverse haplotype structures to fine-map nine loci with a posterior probability >0.8 and globally assessed the heterogeneity of known risk factors across populations. Additionally, we compared the generalizability of multi-ancestry- and single-ancestry-derived polygenic risk scores in a three-way admixed Colombian population. Our findings highlight the importance of multi-ancestry representation in uncovering and understanding putative factors that contribute to risk of Alzheimer’s disease and related dementias.

Published
2022
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6. A connectome and analysis of the adult Drosophila central brain

Author

Temour Tokhi, Tom Dolafi, Nneoma Okeoma, Tanya Wolff, Philip M Hubbard, Kazunori Shinomiya, Madelaine K Robertson, Gerald M. Rubin, Gregory S.X.E. Jefferis, Christopher J Knecht, Laramie Leavitt, Alia Suleiman, Satoko Takemura, Christopher Ordish, Jody Clements, Ian A. Meinertzhagen, Alexander Shakeel Bates, Takashi Kawase, Samantha Finley, Nicholas Padilla, Jackie Swift, C. Shan Xu, Stuart Berg, Tyler Paterson, Ashley L Scott, Erika Neace, Shirley Lauchie, Sean M Ryan, Emily M Joyce, Shin-ya Takemura, Tim Blakely, Michael A Cook, Christopher Patrick, Bryon Eubanks, Audrey Francis, Robert Svirskas, William T. Katz, Eric T. Trautman, Caroline Mooney, Ting Zhao, Nicole A Kirk, Megan Sammons, Brandon S Canino, Reed A. George, Louis K. Scheffer, Jolanta A. Borycz, Jon Thomson Rymer, Natasha Cheatham, Dagmar Kainmueller, Gary B. Huang, Khaled Khairy, Nicole Neubarth, Elliott E Phillips, John A. Bogovic, Neha Rampally, Larry Lindsey, Viren Jain, David G. Ackerman, Jane Anne Horne, Kelli Fairbanks, Lowell Umayam, Jens Goldammer, Emily M Phillips, Donald J. Olbris, Feng Li, Emily A Manley, Philipp Schlegel, Hideo Otsuna, Marta Costa, Stephen M. Plaza, Omotara Ogundeyi, Samantha Ballinger, Charli Maldonado, Kelsey Smith, Gary Patrick Hopkins, Vivek Jayaraman, Emily Tenshaw, Julie Kovalyak, Peter H. Li, Tansy Yang, Masayoshi Ito, Miatta Ndama, Claire Smith, Michał Januszewski, Alanna Lohff, SungJin Kim, Anne K Scott, Kei Ito, Iris Talebi, Jeremy Maitlin-Shepard, Nora Forknall, Marisa Dreher, Harald F. Hess, Sari McLin, Patricia K. Rivlin, Dennis A Bailey, Kenneth J. Hayworth, Octave Duclos, Caitlin Ribeiro, John J. Walsh, Zhiyuan Lu, Dorota Tarnogorska, Ruchi Parekh, Aya Shinomiya, Stephan Saalfeld, Margaret A Sobeski, Natalie L Smith, Chelsea X Alvarado, Scheffer, Louis K [0000-0002-3289-6564], Xu, C Shan [0000-0002-8564-7836], Januszewski, Michal [0000-0002-3480-2744], Lu, Zhiyuan [0000-0002-4128-9774], Takemura, Shin-ya [0000-0003-2400-6426], Huang, Gary B [0000-0002-9606-3510], Shinomiya, Kazunori [0000-0003-0262-6421], Maitlin-Shepard, Jeremy [0000-0001-8453-7961], Hubbard, Philip M [0000-0002-6746-5035], Katz, William T [0000-0002-9417-6212], Ackerman, David [0000-0003-0172-6594], Blakely, Tim [0000-0003-0995-5471], Bogovic, John [0000-0002-4829-9457], Kainmueller, Dagmar [0000-0002-9830-2415], Khairy, Khaled A [0000-0002-9274-5928], Li, Peter H [0000-0001-6193-4454], Trautman, Eric T [0000-0001-8588-0569], Bates, Alexander S [0000-0002-1195-0445], Goldammer, Jens [0000-0002-5623-8339], Wolff, Tanya [0000-0002-8681-1749], Svirskas, Robert [0000-0001-8374-6008], Schlegel, Philipp [0000-0002-5633-1314], Knecht, Christopher J [0000-0002-5663-5967], Alvarado, Chelsea X [0000-0002-5973-7512], Bailey, Dennis A [0000-0002-4675-8373], Borycz, Jolanta A [0000-0002-4402-9230], Canino, Brandon S [0000-0002-8454-865X], Cook, Michael [0000-0002-7892-6845], Dreher, Marisa [0000-0002-0041-9229], Eubanks, Bryon [0000-0002-9288-2009], Fairbanks, Kelli [0000-0002-6601-4830], Finley, Samantha [0000-0002-8086-206X], Forknall, Nora [0000-0003-2139-7599], Francis, Audrey [0000-0003-1974-7174], Joyce, Emily M [0000-0001-5794-6321], Kovalyak, Julie [0000-0001-7864-7734], Lauchie, Shirley A [0000-0001-8223-9522], Lohff, Alanna [0000-0002-1242-1836], McLin, Sari [0000-0002-9120-1136], Patrick, Christopher M [0000-0001-8830-1892], Phillips, Elliott E [0000-0002-4918-2058], Phillips, Emily M [0000-0001-7615-301X], Robertson, Madelaine K [0000-0002-1764-0245], Rymer, Jon Thomson [0000-0002-4271-6774], Ryan, Sean M [0000-0002-8879-6108], Sammons, Megan [0000-0003-4516-5928], Shinomiya, Aya [0000-0002-6358-9567], Smith, Natalie L [0000-0002-8271-9873], Swift, Jackie [0000-0003-1321-8183], Takemura, Satoko [0000-0002-2863-0050], Talebi, Iris [0000-0002-0173-8053], Tarnogorska, Dorota [0000-0002-7063-6165], Walsh, John J [0000-0002-7176-4708], Yang, Tansy [0000-0003-1131-0410], Horne, Jane Anne [0000-0001-9673-2692], Parekh, Ruchi [0000-0002-8060-2807], Jayaraman, Vivek [0000-0003-3680-7378], Costa, Marta [0000-0001-5948-3092], Jefferis, Gregory SXE [0000-0002-0587-9355], Ito, Kei [0000-0002-7274-5533], Saalfeld, Stephan [0000-0002-4106-1761], Rubin, Gerald M [0000-0001-8762-8703], Hess, Harald F [0000-0003-3000-1533], Plaza, Stephen M [0000-0001-7425-8555], Apollo - University of Cambridge Repository, Takemura, Shin-Ya [0000-0003-2400-6426], and Jefferis, Gregory Sxe [0000-0002-0587-9355]

Subjects
Male, Computer science, computational biology, 0302 clinical medicine, Drosophila Proteins, Research article, Biology (General), Neurons, Cognitive science, 0303 health sciences, biology, D. melanogaster, General Neuroscience, connectome, Brain, systems biology, graph properties, General Medicine, Human brain, Drosophila melanogaster, medicine.anatomical_structure, Connectome, Medicine, Drosophila, Female, synapse detecton, Insight, Function and Dysfunction of the Nervous System, cell types, Research Article, Computational and Systems Biology, brain regions, Connectomes, QH301-705.5, Ubiquitin-Protein Ligases, Science, connectome reconstuction methods, Small mammal, Central region, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, medicine, Animals, 030304 developmental biology, General Immunology and Microbiology, biology.organism_classification, synapse detection, Synapses, 030217 neurology & neurosurgery, Neuroscience
Abstract

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly’s brain., eLife digest Animal brains of all sizes, from the smallest to the largest, work in broadly similar ways. Studying the brain of any one animal in depth can thus reveal the general principles behind the workings of all brains. The fruit fly Drosophila is a popular choice for such research. With about 100,000 neurons – compared to some 86 billion in humans – the fly brain is small enough to study at the level of individual cells. But it nevertheless supports a range of complex behaviors, including navigation, courtship and learning. Thanks to decades of research, scientists now have a good understanding of which parts of the fruit fly brain support particular behaviors. But exactly how they do this is often unclear. This is because previous studies showing the connections between cells only covered small areas of the brain. This is like trying to understand a novel when all you can see is a few isolated paragraphs. To solve this problem, Scheffer, Xu, Januszewski, Lu, Takemura, Hayworth, Huang, Shinomiya et al. prepared the first complete map of the entire central region of the fruit fly brain. The central brain consists of approximately 25,000 neurons and around 20 million connections. To prepare the map – or connectome – the brain was cut into very thin 8nm slices and photographed with an electron microscope. A three-dimensional map of the neurons and connections in the brain was then reconstructed from these images using machine learning algorithms. Finally, Scheffer et al. used the new connectome to obtain further insights into the circuits that support specific fruit fly behaviors. The central brain connectome is freely available online for anyone to access. When used in combination with existing methods, the map will make it easier to understand how the fly brain works, and how and why it can fail to work correctly. Many of these findings will likely apply to larger brains, including our own. In the long run, studying the fly connectome may therefore lead to a better understanding of the human brain and its disorders. Performing a similar analysis on the brain of a small mammal, by scaling up the methods here, will be a likely next step along this path.

Published
2020

7. Author response: A connectome and analysis of the adult Drosophila central brain

Author

Dennis A Bailey, Kenneth J. Hayworth, Aya Shinomiya, Madelaine K Robertson, Tim Blakely, C. Shan Xu, Temour Tokhi, Jon Thomson Rymer, Nicole Neubarth, Zhiyuan Lu, Dorota Tarnogorska, Shirley Lauchie, Sean M Ryan, Nneoma Okeoma, Erika Neace, Khaled Khairy, Emily M Phillips, Margaret A Sobeski, Bryon Eubanks, Christopher Patrick, Marisa Dreher, Natalie L Smith, Philipp Schlegel, John A. Bogovic, David G. Ackerman, Jane Anne Horne, Tom Dolafi, Gary B. Huang, Kelli Fairbanks, Claire Smith, Michał Januszewski, Octave Duclos, Satoko Takemura, Christopher Ordish, Chelsea X Alvarado, Jody Clements, Viren Jain, Samantha Finley, John J. Walsh, Nicole A Kirk, Kelsey Smith, Omotara Ogundeyi, Takashi Kawase, Reed A. George, Tyler Paterson, Laramie Leavitt, Kazunori Shinomiya, SungJin Kim, Christopher J Knecht, Nicholas Padilla, Anne K Scott, Tansy Yang, Ashley L Scott, Hideo Otsuna, Jeremy Maitlin-Shepard, Marta Costa, Nora Forknall, Stuart Berg, Alia Suleiman, Harald F. Hess, Audrey Francis, Donald J. Olbris, Caroline Mooney, Emily M Joyce, Eric T. Trautman, Gerald M. Rubin, Jackie Swift, Philip M Hubbard, Ting Zhao, Brandon S Canino, Gary Patrick Hopkins, Kei Ito, Jolanta A. Borycz, Shin-ya Takemura, Masayoshi Ito, Stephen M. Plaza, Ian A. Meinertzhagen, Louis K. Scheffer, Dagmar Kainmueller, Larry Lindsey, Miatta Ndama, Elliott E Phillips, Lowell Umayam, Jens Goldammer, Vivek Jayaraman, Emily Tenshaw, Gregory S.X.E. Jefferis, Alexander Shakeel Bates, William T. Katz, Sari McLin, Neha Rampally, Emily A Manley, Patricia K. Rivlin, Charli Maldonado, Peter H. Li, Samantha Ballinger, Tanya Wolff, Megan Sammons, Julie Kovalyak, Stephan Saalfeld, Alanna Lohff, Natasha Cheatham, Iris Talebi, Michael A Cook, Robert Svirskas, Feng Li, Caitlin Ribeiro, and Ruchi Parekh

Subjects
biology, Connectome, Drosophila (subgenus), biology.organism_classification, Neuroscience
Published
2020
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8. A Connectome and Analysis of the Adult Drosophila Central Brain

Author

C. Shan Xu, Jackie Swift, Miatta Ndama, Philipp Schlegel, SungJin Kim, Khaled Khairy, Christopher Ordish, Omotara Ogundeyi, Kelli Fairbanks, Kenneth J. Hayworth, Samantha Finley, Natasha Cheatham, Nora Forknall, Laramie Leavitt, Temour Tokhi, Nicole A Kirk, Shin-ya Takemura, Nneoma Okeoma, Robert Svirskas, Kazunori Shinomiya, Madelaine K Robertson, Caitlin Ribeiro, Christopher J Knecht, Emily M Joyce, Margaret A Sobeski, Ruchi Parekh, Alia Suleiman, Shirley Lauchie, Sean M Ryan, Iris Talebi, Harald F. Hess, Christopher Patrick, William T. Katz, Stephen M. Plaza, Dagmar Kainmueller, Feng Li, Natalie L Smith, Michał Januszewski, Satoko Takemura, Chelsea X Alvarado, Michael A Cook, Sari McLin, Tom Dolafi, Hideo Otsuna, Jeremy Maitin-Shepard, Kei Ito, Viren Jain, Donald J. Olbris, Tanya Wolff, Takashi Kawase, Tyler Paterson, Patricia K. Rivlin, Jolanta A. Borycz, Ashley L Scott, Claire Smith, Nicholas Padilla, Gary Patrick Hopkins, Vivek Jayaraman, Emily Tenshaw, Zhiyuan Lu, Stuart Berg, Dorota Tarnogorska, Samantha Ballinger, Audrey Francis, Julie Kovalyak, Ting Zhao, Anne K Scott, Alanna Lohff, Caroline Mooney, Brandon S Canino, Gary B. Huang, Jon Thomson Rymer, Marisa Dreher, Jody Clements, Nicole Neubarth, Larry Lindsey, John A. Bogovic, David G. Ackerman, Jane Anne Horne, Louis K. Scheffer, Elliott E Phillips, Lowell Umayam, Jens Goldammer, Eric T. Trautman, Emily A Manley, Charli Maldonado, Peter H. Li, Octave Duclos, John J. Walsh, Stephan Saalfeld, Reed A. George, Gerald M. Rubin, Philip M Hubbard, Ian A. Meinertzhagen, Emily M Phillips, Masayoshi Ito, Erika Neace, Kelsey Smith, Bryon Eubanks, Neha Rampally, Tim Blakely, Tansy Yang, Dennis A Bailey, Megan Sammons, and Aya Shinomiya

Subjects
0303 health sciences, Cell type, biology, Computer science, biology.organism_classification, Synapse, 03 medical and health sciences, 0302 clinical medicine, Connectome, Biological neural network, Drosophila melanogaster, Function and Dysfunction of the Nervous System, Neuroscience, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly’s brain.

Published
2020
Full Text
View/download PDF

9. A Connectome of the Adult Drosophila Central Brain

Author

Audrey Francis, Ting Zhao, Feng Li, Megan Sammons, Madelaine K Robertson, SungJin Kim, Tyler Paterson, Philipp Schlegel, Chelsea X Alvarado, Viren Jain, Brandon S Canino, Omotara Ogundeyi, Nora Forknall, Dagmar Kainmueller, Tansy Yang, Natasha Cheatham, Neha Rampally, Caitlin Ribeiro, Kimothy L. Smith, Emily M Phillips, Ruchi Parekh, Jackie Swift, Donald J. Olbris, Takashi Kawase, Jon Thomson Rymer, Zhiyuan Lu, Nicholas Padilla, Christopher Ordish, Dorota Tarnogorska, Nicole Neubarth, Aya Shinomiya, Miatta Ndama, Samantha Finley, Stuart Berg, Erika Neace, Bryon Eubanks, John A. Bogovic, David G. Ackerman, Robert Svirskas, Sari McLin, Emily A Manley, Jane Anne Horne, Michael A Cook, Samantha Ballinger, Michał Januszewski, Jeremy Maitin-Shepard, Caroline Mooney, Nicole A Kirk, Shin-ya Takemura, Iris Talebi, Temour Tokhi, Kei K. Ito, Khaled Khairy, Stephen M. Plaza, Julie Kovalyak, Patricia K. Rivlin, Emily M Joyce, Kelli Fairbanks, Philip M Hubbard, Charli Maldonado, Nneoma Okeoma, Hideo Otsuna, Laurence F. Lindsey, Tim Blakely, Gerald M. Rubin, Alanna Lohff, William T. Katz, Anne K Scott, Mutsumi Ito, Peter H. Li, Ian A. Meinertzhagen, Natalie L Smith, Gary B. Huang, Dennis A Bailey, Reed A. George, Kenneth J. Hayworth, Tom Dolafi, Marisa Dreher, Tanya Wolff, Kazunori Shinomiya, Harald F. Hess, E.T. Troutman, Christopher J Knecht, Gary Patrick Hopkins, Alia Suleiman, Vivek Jayaraman, Emily Tenshaw, Octave Duclos, John J. Walsh, Stephan Saalfeld, Louis K. Scheffer, Elliott E Phillips, Lowell Umayam, Jens Goldammer, Sobeski, Jody Clements, Ashley L Scott, Shirley Lauchie, Sean M Ryan, Christopher Patrick, Jolanta A. Borycz, Claire Smith, C.S. Xu, and Laramie Leavitt

Subjects
Cell type, Computer science, Cell, Machine learning, computer.software_genre, Synapse, 03 medical and health sciences, 0302 clinical medicine, medicine, Biological neural network, 030304 developmental biology, Structure (mathematical logic), 0303 health sciences, biology, business.industry, Motor control, biology.organism_classification, Associative learning, medicine.anatomical_structure, Mushroom bodies, Identity (object-oriented programming), Connectome, Artificial intelligence, Drosophila melanogaster, Function and Dysfunction of the Nervous System, business, computer, 030217 neurology & neurosurgery
Abstract

The neural circuits responsible for behavior remain largely unknown. Previous efforts have reconstructed the complete circuits of small animals, with hundreds of neurons, and selected circuits for larger animals. Here we (the FlyEM project at Janelia and collaborators at Google) summarize new methods and present the complete circuitry of a large fraction of the brain of a much more complex animal, the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses, and proofread such large data sets; new methods that define cell types based on connectivity in addition to morphology; and new methods to simplify access to a large and evolving data set. From the resulting data we derive a better definition of computational compartments and their connections; an exhaustive atlas of cell examples and types, many of them novel; detailed circuits for most of the central brain; and exploration of the statistics and structure of different brain compartments, and the brain as a whole. We make the data public, with a web site and resources specifically designed to make it easy to explore, for all levels of expertise from the expert to the merely curious. The public availability of these data, and the simplified means to access it, dramatically reduces the effort needed to answer typical circuit questions, such as the identity of upstream and downstream neural partners, the circuitry of brain regions, and to link the neurons defined by our analysis with genetic reagents that can be used to study their functions.Note: In the next few weeks, we will release a series of papers with more involved discussions. One paper will detail the hemibrain reconstruction with more extensive analysis and interpretation made possible by this dense connectome. Another paper will explore the central complex, a brain region involved in navigation, motor control, and sleep. A final paper will present insights from the mushroom body, a center of multimodal associative learning in the fly brain.

Published
2020
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