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1. A whole-brain monosynaptic input connectome to neuron classes in mouse visual cortex

Author

Yao, Shenqin, Wang, Quanxin, Hirokawa, Karla E., Ouellette, Benjamin, Ahmed, Ruweida, Bomben, Jasmin, Brouner, Krissy, Casal, Linzy, Caldejon, Shiella, Cho, Andy, Dotson, Nadezhda I., Daigle, Tanya L., Egdorf, Tom, Enstrom, Rachel, Gary, Amanda, Gelfand, Emily, Gorham, Melissa, Griffin, Fiona, Gu, Hong, Hancock, Nicole, Howard, Robert, Kuan, Leonard, Lambert, Sophie, Lee, Eric Kenji, Luviano, Jennifer, Mace, Kyla, Maxwell, Michelle, Mortrud, Marty T., Naeemi, Maitham, Nayan, Chelsea, Ngo, Nhan-Kiet, Nguyen, Thuyanh, North, Kat, Ransford, Shea, Ruiz, Augustin, Seid, Sam, Swapp, Jackie, Taormina, Michael J., Wakeman, Wayne, Zhou, Thomas, Nicovich, Philip R., Williford, Ali, Potekhina, Lydia, McGraw, Medea, Ng, Lydia, Groblewski, Peter A., Tasic, Bosiljka, Mihalas, Stefan, Harris, Julie A., Cetin, Ali, and Zeng, Hongkui

Published
2023
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2. Morphological diversity of single neurons in molecularly defined cell types

Author

Peng, Hanchuan, Xie, Peng, Liu, Lijuan, Kuang, Xiuli, Wang, Yimin, Qu, Lei, Gong, Hui, Jiang, Shengdian, Li, Anan, Ruan, Zongcai, Ding, Liya, Yao, Zizhen, Chen, Chao, Chen, Mengya, Daigle, Tanya L., Dalley, Rachel, Ding, Zhangcan, Duan, Yanjun, Feiner, Aaron, He, Ping, Hill, Chris, Hirokawa, Karla E., Hong, Guodong, Huang, Lei, Kebede, Sara, Kuo, Hsien-Chi, Larsen, Rachael, Lesnar, Phil, Li, Longfei, Li, Qi, Li, Xiangning, Li, Yaoyao, Li, Yuanyuan, Liu, An, Lu, Donghuan, Mok, Stephanie, Ng, Lydia, Nguyen, Thuc Nghi, Ouyang, Qiang, Pan, Jintao, Shen, Elise, Song, Yuanyuan, Sunkin, Susan M., Tasic, Bosiljka, Veldman, Matthew B., Wakeman, Wayne, Wan, Wan, Wang, Peng, Wang, Quanxin, Wang, Tao, Wang, Yaping, Xiong, Feng, Xiong, Wei, Xu, Wenjie, Ye, Min, Yin, Lulu, Yu, Yang, Yuan, Jia, Yuan, Jing, Yun, Zhixi, Zeng, Shaoqun, Zhang, Shichen, Zhao, Sujun, Zhao, Zijun, Zhou, Zhi, Huang, Z. Josh, Esposito, Luke, Hawrylycz, Michael J., Sorensen, Staci A., Yang, X. William, Zheng, Yefeng, Gu, Zhongze, Xie, Wei, Koch, Christof, Luo, Qingming, Harris, Julie A., Wang, Yun, and Zeng, Hongkui

Published
2021
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3. Cellular anatomy of the mouse primary motor cortex

Author

Muñoz-Castañeda, Rodrigo, Zingg, Brian, Matho, Katherine S., Chen, Xiaoyin, Wang, Quanxin, Foster, Nicholas N., Li, Anan, Narasimhan, Arun, Hirokawa, Karla E., Huo, Bingxing, Bannerjee, Samik, Korobkova, Laura, Park, Chris Sin, Park, Young-Gyun, Bienkowski, Michael S., Chon, Uree, Wheeler, Diek W., Li, Xiangning, Wang, Yun, Naeemi, Maitham, Xie, Peng, Liu, Lijuan, Kelly, Kathleen, An, Xu, Attili, Sarojini M., Bowman, Ian, Bludova, Anastasiia, Cetin, Ali, Ding, Liya, Drewes, Rhonda, D’Orazi, Florence, Elowsky, Corey, Fischer, Stephan, Galbavy, William, Gao, Lei, Gillis, Jesse, Groblewski, Peter A., Gou, Lin, Hahn, Joel D., Hatfield, Joshua T., Hintiryan, Houri, Huang, Junxiang Jason, Kondo, Hideki, Kuang, Xiuli, Lesnar, Philip, Li, Xu, Li, Yaoyao, Lin, Mengkuan, Lo, Darrick, Mizrachi, Judith, Mok, Stephanie, Nicovich, Philip R., Palaniswamy, Ramesh, Palmer, Jason, Qi, Xiaoli, Shen, Elise, Sun, Yu-Chi, Tao, Huizhong W., Wakemen, Wayne, Wang, Yimin, Yao, Shenqin, Yuan, Jing, Zhan, Huiqing, Zhu, Muye, Ng, Lydia, Zhang, Li I., Lim, Byung Kook, Hawrylycz, Michael, Gong, Hui, Gee, James C., Kim, Yongsoo, Chung, Kwanghun, Yang, X. William, Peng, Hanchuan, Luo, Qingming, Mitra, Partha P., Zador, Anthony M., Zeng, Hongkui, Ascoli, Giorgio A., Josh Huang, Z., Osten, Pavel, Harris, Julie A., and Dong, Hong-Wei

Published
2021
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4. Agenesis of the Corpus Callosum Due to Defective Glial Wedge Formation in Lhx2 Mutant Mice

Author

Chinn, Gregory A, Hirokawa, Karla E, Chuang, Tony M, Urbina, Cecilia, Patel, Fenil, Fong, Jeanette, Funatsu, Nobuo, and Monuki, Edwin S

Subjects
Biomedical and Clinical Sciences, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Neurological, Agenesis of Corpus Callosum, Animals, Basic Helix-Loop-Helix Transcription Factors, DNA-Binding Proteins, Disease Models, Animal, Female, Glial Fibrillary Acidic Protein, Homeodomain Proteins, Ki-67 Antigen, LIM-Homeodomain Proteins, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Neocortex, Nerve Tissue Proteins, Nestin, Neuroglia, Peripheral Nervous System Diseases, RNA, Untranslated, Repressor Proteins, T-Box Domain Proteins, Transcription Factors, Tumor Suppressor Proteins, agenesis of the corpus callosum, Cre-lox, glial wedge, Lhx2, mouse, Psychology, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

Establishment of the corpus callosum involves coordination between callosal projection neurons and multiple midline structures, including the glial wedge (GW) rostrally and hippocampal commissure caudally. GW defects have been associated with agenesis of the corpus callosum (ACC). Here we show that conditional Lhx2 inactivation in cortical radial glia using Emx1-Cre or Nestin-Cre drivers results in ACC. The ACC phenotype was characterized by aberrant ventrally projecting callosal axons rather than Probst bundles, and was 100% penetrant on 2 different mouse strain backgrounds. Lhx2 inactivation in postmitotic cortical neurons using Nex-Cre mice did not result in ACC, suggesting that the mutant phenotype was not autonomous to the callosal projection neurons. Instead, ACC was associated with an absent hippocampal commissure and a markedly reduced to absent GW. Expression studies demonstrated strong Lhx2 expression in the normal GW and in its radial glial progenitors, with absence of Lhx2 resulting in normal Emx1 and Sox2 expression, but premature exit from the cell cycle based on EdU-Ki67 double labeling. These studies define essential roles for Lhx2 in GW, hippocampal commissure, and corpus callosum formation, and suggest that defects in radial GW progenitors can give rise to ACC.

Published
2015

5. Connecting single-cell transcriptomes to projectomes in mouse visual cortex

Author

Sorensen, Staci A., primary, Gouwens, Nathan W., additional, Wang, Yun, additional, Mallory, Matt, additional, Budzillo, Agata, additional, Dalley, Rachel, additional, Lee, Brian, additional, Gliko, Olga, additional, Kuo, Hsien-chi, additional, Kuang, Xiuli, additional, Mann, Rusty, additional, Ahmadinia, Leila, additional, Alfiler, Lauren, additional, Baftizadeh, Fahimeh, additional, Baker, Katherine, additional, Bannick, Sarah, additional, Bertagnolli, Darren, additional, Bickley, Kris, additional, Bohn, Phil, additional, Brown, Dillan, additional, Bomben, Jasmine, additional, Brouner, Krissy, additional, Chen, Chao, additional, Chen, Kai, additional, Chvilicek, Maggie, additional, Collman, Forrest, additional, Daigle, Tanya, additional, Dawes, Tim, additional, de Frates, Rebecca, additional, Dee, Nick, additional, DePartee, Maxwell, additional, Egdorf, Tom, additional, El-Hifnawi, Laila, additional, Enstrom, Rachel, additional, Esposito, Luke, additional, Farrell, Colin, additional, Gala, Rohan, additional, Glomb, Andrew, additional, Gamlin, Clare, additional, Gary, Amanda, additional, Goldy, Jeff, additional, Gu, Hong, additional, Hadley, Kristen, additional, Hawrylycz, Mike, additional, Henry, Alex, additional, Hill, Dijon, additional, Hirokawa, Karla E., additional, Huang, Zili, additional, Johnson, Katelyn, additional, Juneau, Zoe, additional, Kebede, Sara, additional, Kim, Lisa, additional, Lee, Changkyu, additional, Lesnar, Phil, additional, Li, Anan, additional, Li, Yaoyao, additional, Liang, Elizabeth, additional, Link, Katie, additional, Maxwell, Michelle, additional, McGraw, Medea, additional, McMillen, Delissa A., additional, Mukora, Alice, additional, Ng, Lindsay, additional, Ochoa, Thomas, additional, Oldre, Aaron, additional, Park, Daniel, additional, Pom, Christina Alice, additional, Popovich, Zoran, additional, Potekhina, Lydia, additional, Rajanbabu, Ram, additional, Ransford, Shea, additional, Reding, Melissa, additional, Ruiz, Augustin, additional, Sandman, David, additional, Siverts, La’Akea, additional, Smith, Kimberly A., additional, Stoecklin, Michelle, additional, Sulc, Josef, additional, Tieu, Michael, additional, Ting, Jonathan, additional, Trinh, Jessica, additional, Vargas, Sara, additional, Vumbaco, Dave, additional, Walker, Miranda, additional, Wang, Micheal, additional, Wanner, Adrian, additional, Waters, Jack, additional, Williams, Grace, additional, Wilson, Julia, additional, Xiong, Wei, additional, Lein, Ed, additional, Berg, Jim, additional, Kalmbach, Brian, additional, Yao, Shenqin, additional, Gong, Hui, additional, Luo, Qingming, additional, Ng, Lydia, additional, Sümbül, Uygar, additional, Jarsky, Tim, additional, Yao, Zizhen, additional, Tasic, Bosiljka, additional, and Zeng, Hongkui, additional

Published
2023
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6. Hierarchical organization of cortical and thalamic connectivity

Author

Harris, Julie A., Mihalas, Stefan, Hirokawa, Karla E., Whitesell, Jennifer D., Choi, Hannah, Bernard, Amy, and Bohn, Phillip

Subjects
Neural circuitry -- Structure, Thalamus -- Comparative analysis, Cerebral cortex -- Comparative analysis, Memory -- Analysis, Connectionism -- Analysis, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The mammalian cortex is a laminar structure containing many areas and cell types that are densely interconnected in complex ways, and for which generalizable principles of organization remain mostly unknown. Here we describe a major expansion of the Allen Mouse Brain Connectivity Atlas resource.sup.1, involving around a thousand new tracer experiments in the cortex and its main satellite structure, the thalamus. We used Cre driver lines (mice expressing Cre recombinase) to comprehensively and selectively label brain-wide connections by layer and class of projection neuron. Through observations of axon termination patterns, we have derived a set of generalized anatomical rules to describe corticocortical, thalamocortical and corticothalamic projections. We have built a model to assign connection patterns between areas as either feedforward or feedback, and generated testable predictions of hierarchical positions for individual cortical and thalamic areas and for cortical network modules. Our results show that cell-class-specific connections are organized in a shallow hierarchy within the mouse corticothalamic network. Using mouse lines in which subsets of neurons are genetically labelled, the authors provide generalized anatomical rules for connections within and between the cortex and thalamus., Author(s): Julie A. Harris [sup.1] , Stefan Mihalas [sup.1] , Karla E. Hirokawa [sup.1] , Jennifer D. Whitesell [sup.1] , Hannah Choi [sup.1] [sup.2] , Amy Bernard [sup.1] , Phillip [...]

Published
2019
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7. Shared and distinct transcriptomic cell types across neocortical areas

Author

Tasic, Bosiljka, Yao, Zizhen, Graybuck, Lucas T., Smith, Kimberly A., Nguyen, Thuc Nghi, Bertagnolli, Darren, Goldy, Jeff, Garren, Emma, Economo, Michael N., Viswanathan, Sarada, Penn, Osnat, Bakken, Trygve, Menon, Vilas, Miller, Jeremy, Fong, Olivia, Hirokawa, Karla E., Lathia, Kanan, Rimorin, Christine, Tieu, Michael, Larsen, Rachael, Casper, Tamara, Barkan, Eliza, Kroll, Matthew, Parry, Sheana, Shapovalova, Nadiya V., Hirschstein, Daniel, Pendergraft, Julie, Sullivan, Heather A., Kim, Tae Kyung, Szafer, Aaron, Dee, Nick, Groblewski, Peter, Wickersham, Ian, Cetin, Ali, Harris, Julie A., Levi, Boaz P., Sunkin, Susan M., Madisen, Linda, Daigle, Tanya L., Looger, Loren, Bernard, Amy, Phillips, John, Lein, Ed, Hawrylycz, Michael, Svoboda, Karel, Jones, Allan R., Koch, Christof, and Zeng, Hongkui

Published
2018
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9. Regional and cell-type-specific afferent and efferent projections of the mouse claustrum

Author

Wang, Quanxin, primary, Wang, Yun, additional, Kuo, Hsien-Chi, additional, Xie, Peng, additional, Kuang, Xiuli, additional, Hirokawa, Karla E., additional, Naeemi, Maitham, additional, Yao, Shenqin, additional, Mallory, Matt, additional, Ouellette, Ben, additional, Lesnar, Phil, additional, Li, Yaoyao, additional, Ye, Min, additional, Chen, Chao, additional, Xiong, Wei, additional, Ahmadinia, Leila, additional, El-Hifnawi, Laila, additional, Cetin, Ali, additional, Sorensen, Staci A., additional, Harris, Julie A., additional, Zeng, Hongkui, additional, and Koch, Christof, additional

Published
2023
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10. A whole-brain monosynaptic input connectome to neuron classes in mouse visual cortex

Author

Yao, Shenqin, primary, Wang, Quanxin, additional, Hirokawa, Karla E., additional, Ouellette, Benjamin, additional, Ahmed, Ruweida, additional, Bomben, Jasmin, additional, Brouner, Krissy, additional, Casal, Linzy, additional, Caldejon, Shiella, additional, Cho, Andy, additional, Dotson, Nadezhda I., additional, Daigle, Tanya L., additional, Egdorf, Tom, additional, Enstrom, Rachel, additional, Gary, Amanda, additional, Gelfand, Emily, additional, Gorham, Melissa, additional, Griffin, Fiona, additional, Gu, Hong, additional, Hancock, Nicole, additional, Howard, Robert, additional, Kuan, Leonard, additional, Lambert, Sophie, additional, Lee, Eric Kenji, additional, Luviano, Jennifer, additional, Mace, Kyla, additional, Maxwell, Michelle, additional, Mortrud, Marty T., additional, Naeemi, Maitham, additional, Nayan, Chelsea, additional, Ngo, Nhan-Kiet, additional, Nguyen, Thuyanh, additional, North, Kat, additional, Ransford, Shea, additional, Ruiz, Augustin, additional, Seid, Sam, additional, Swapp, Jackie, additional, Taormina, Michael J., additional, Wakeman, Wayne, additional, Zhou, Thomas, additional, Nicovich, Philip R., additional, Williford, Ali, additional, Potekhina, Lydia, additional, McGraw, Medea, additional, Ng, Lydia, additional, Groblewski, Peter A., additional, Tasic, Bosiljka, additional, Mihalas, Stefan, additional, Harris, Julie A., additional, Cetin, Ali, additional, and Zeng, Hongkui, additional

Published
2022
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11. A Suite of Transgenic Driver and Reporter Mouse Lines with Enhanced Brain-Cell-Type Targeting and Functionality

Author

Daigle, Tanya L., Madisen, Linda, Hage, Travis A., Valley, Matthew T., Knoblich, Ulf, Larsen, Rylan S., Takeno, Marc M., Huang, Lawrence, Gu, Hong, Larsen, Rachael, Mills, Maya, Bosma-Moody, Alice, Siverts, La’ Akea, Walker, Miranda, Graybuck, Lucas T., Yao, Zizhen, Fong, Olivia, Nguyen, Thuc Nghi, Garren, Emma, Lenz, Garreck H., Chavarha, Mariya, Pendergraft, Julie, Harrington, James, Hirokawa, Karla E., Harris, Julie A., Nicovich, Philip R., McGraw, Medea J., Ollerenshaw, Douglas R., Smith, Kimberly A., Baker, Christopher A., Ting, Jonathan T., Sunkin, Susan M., Lecoq, Jérôme, Lin, Michael Z., Boyden, Edward S., Murphy, Gabe J., da Costa, Nuno M., Waters, Jack, Li, Lu, Tasic, Bosiljka, Zeng, Hongkui, Daigle, Tanya L., Madisen, Linda, Hage, Travis A., Valley, Matthew T., Knoblich, Ulf, Larsen, Rylan S., Takeno, Marc M., Huang, Lawrence, Gu, Hong, Larsen, Rachael, Mills, Maya, Bosma-Moody, Alice, Siverts, La’ Akea, Walker, Miranda, Graybuck, Lucas T., Yao, Zizhen, Fong, Olivia, Nguyen, Thuc Nghi, Garren, Emma, Lenz, Garreck H., Chavarha, Mariya, Pendergraft, Julie, Harrington, James, Hirokawa, Karla E., Harris, Julie A., Nicovich, Philip R., McGraw, Medea J., Ollerenshaw, Douglas R., Smith, Kimberly A., Baker, Christopher A., Ting, Jonathan T., Sunkin, Susan M., Lecoq, Jérôme, Lin, Michael Z., Boyden, Edward S., Murphy, Gabe J., da Costa, Nuno M., Waters, Jack, Li, Lu, Tasic, Bosiljka, and Zeng, Hongkui

Abstract

An expanded toolkit of transgenic mouse lines for exploring the organization, function, and development of mammalian neural circuits.

Published
2022

13. Regional and cell type-specific afferent and efferent projections of the mouse claustrum

Author

Wang, Quanxin, primary, Wang, Yun, additional, Xie, Peng, additional, Kuo, Hsien-Chi, additional, Hirokawa, Karla E, additional, Naeemi, Maitham, additional, Yao, Shenqin, additional, Ouellette, Ben, additional, Mallory, Matt, additional, Lesnar, Phil, additional, Kuang, Xiuli, additional, Li, Yaoyao, additional, Ye, Min, additional, Chen, Chao, additional, Xiong, Wei, additional, Ahmadinia, Leila, additional, El-Hifnawi, Laila, additional, Cetin, Ali, additional, Harris, Julie A, additional, Zeng, Hongkui, additional, and Koch, Christof, additional

Published
2022
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14. A multimodal cell census and atlas of the mammalian primary motor cortex

Author

Callaway, Edward M., Dong, Hong-Wei, Ecker, Joseph R., Hawrylycz, Michael J., Huang, Z. Josh, Lein, Ed S., Ngai, John, Osten, Pavel, Ren, Bing, Tolias, Andreas Savas, White, Owen, Zeng, Hongkui, Zhuang, Xiaowei, Ascoli, Giorgio A., Behrens, M. Margarita, Chun, Jerold, Feng, Guoping, Gee, James C., Ghosh, Satrajit S., Halchenko, Yaroslav O., Hertzano, Ronna, Lim, Byung Kook, Martone, Maryann E., Ng, Lydia, Pachter, Lior, Ropelewski, Alexander J., Tickle, Timothy L., Yang, X. William, Zhang, Kun, Bakken, Trygve E., Berens, Philipp, Daigle, Tanya L., Harris, Julie A., Jorstad, Nikolas L., Kalmbach, Brian E., Kobak, Dmitry, Li, Yang Eric, Liu, Hanqing, Matho, Katherine S., Mukamel, Eran A., Naeemi, Maitham, Scala, Federico, Tan, Pengcheng, Ting, Jonathan T., Xie, Fangming, Zhang, Meng, Zhang, Zhuzhu, Zhou, Jingtian, Zingg, Brian, Armand, Ethan, Yao, Zizhen, Bertagnolli, Darren, Casper, Tamara, Crichton, Kirsten, Dee, Nick, Diep, Dinh, Ding, Song-Lin, Dong, Weixiu, Dougherty, Elizabeth L., Fong, Olivia, Goldman, Melissa, Goldy, Jeff, Hodge, Rebecca D., Hu, Lijuan, Keene, C. Dirk, Krienen, Fenna M., Kroll, Matthew, Lake, Blue B., Lathia, Kanan, Linnarsson, Sten, Liu, Christine S., Macosko, Evan Z., McCarroll, Steven A., McMillen, Delissa, Nadaf, Naeem M., Nguyen, Thuc Nghi, Palmer, Carter R., Pham, Thanh, Plongthongkum, Nongluk, Reed, Nora M., Regev, Aviv, Rimorin, Christine, Romanow, William J., Savoia, Steven, Siletti, Kimberly, Smith, Kimberly, Sulc, Josef, Tasic, Bosiljka, Tieu, Michael, Torkelson, Amy, Tung, Herman, van Velthoven, Cindy T. J., Vanderburg, Charles R., Yanny, Anna Marie, Fang, Rongxin, Hou, Xiaomeng, Lucero, Jacinta D., Osteen, Julia K., Pinto-Duarte, Antonio, Poirion, Olivier, Preissl, Sebastian, Wang, Xinxin, Aldridge, Andrew I., Bartlett, Anna, Boggeman, Lara, O’Connor, Carolyn, Castanon, Rosa G., Chen, Huaming, Fitzpatrick, Conor, Luo, Chongyuan, Nery, Joseph R., Nunn, Michael, Rivkin, Angeline C., Tian, Wei, Dominguez, Bertha, Ito-Cole, Tony, Jacobs, Matthew, Jin, Xin, Lee, Cheng-Ta, Lee, Kuo-Fen, Miyazaki, Paula Assakura, Pang, Yan, Rashid, Mohammad, Smith, Jared B., Vu, Minh, Williams, Elora, Biancalani, Tommaso, Booeshaghi, A. Sina, Crow, Megan, Dudoit, Sandrine, Fischer, Stephan, Gillis, Jesse, Hu, Qiwen, Kharchenko, Peter V., Niu, Sheng-Yong, Ntranos, Vasilis, Purdom, Elizabeth, Risso, Davide, de Bézieux, Hector Roux, Somasundaram, Saroja, Street, Kelly, Svensson, Valentine, Vaishnav, Eeshit Dhaval, Van den Berge, Koen, Welch, Joshua D., An, Xu, Bateup, Helen S., Bowman, Ian, Chance, Rebecca K., Foster, Nicholas N., Galbavy, William, Gong, Hui, Gou, Lin, Hatfield, Joshua T., Hintiryan, Houri, Hirokawa, Karla E., Kim, Gukhan, Kramer, Daniel J., Li, Anan, Li, Xiangning, Luo, Qingming, Muñoz-Castañeda, Rodrigo, Stafford, David A., Feng, Zhao, Jia, Xueyan, Jiang, Shengdian, Jiang, Tao, Kuang, Xiuli, Larsen, Rachael, Lesnar, Phil, Li, Yaoyao, Li, Yuanyuan, Liu, Lijuan, Peng, Hanchuan, Qu, Lei, Ren, Miao, Ruan, Zongcai, Shen, Elise, Song, Yuanyuan, Wakeman, Wayne, Wang, Peng, Wang, Yimin, Wang, Yun, Yin, Lulu, Yuan, Jing, Zhao, Sujun, Zhao, Xuan, Narasimhan, Arun, Palaniswamy, Ramesh, Banerjee, Samik, Ding, Liya, Huilgol, Dhananjay, Huo, Bingxing, Kuo, Hsien-Chi, Laturnus, Sophie, Li, Xu, Mitra, Partha P., Mizrachi, Judith, Wang, Quanxin, Xie, Peng, Xiong, Feng, Yu, Yang, Eichhorn, Stephen W., Berg, Jim, Bernabucci, Matteo, Bernaerts, Yves, Cadwell, Cathryn René, Castro, Jesus Ramon, Dalley, Rachel, Hartmanis, Leonard, Horwitz, Gregory D., Jiang, Xiaolong, Ko, Andrew L., Miranda, Elanine, Mulherkar, Shalaka, Nicovich, Philip R., Owen, Scott F., Sandberg, Rickard, Sorensen, Staci A., Tan, Zheng Huan, Allen, Shona, Hockemeyer, Dirk, Lee, Angus Y., Veldman, Matthew B., Adkins, Ricky S., Ament, Seth A., Bravo, Héctor Corrada, Carter, Robert, Chatterjee, Apaala, Colantuoni, Carlo, Crabtree, Jonathan, Creasy, Heather, Felix, Victor, Giglio, Michelle, Herb, Brian R., Kancherla, Jayaram, Mahurkar, Anup, McCracken, Carrie, Nickel, Lance, Olley, Dustin, Orvis, Joshua, Schor, Michael, Hood, Greg, Dichter, Benjamin, Grauer, Michael, Helba, Brian, Bandrowski, Anita, Barkas, Nikolaos, Carlin, Benjamin, D’Orazi, Florence D., Degatano, Kylee, Gillespie, Thomas H., Khajouei, Farzaneh, Konwar, Kishori, Thompson, Carol, Kelly, Kathleen, Mok, Stephanie, Sunkin, Susan, BRAIN Initiative Cell Census Network (BICCN) Corresponding authors, [missing], BICCN contributing principal investigators, [missing], Principal manuscript editors, [missing], Manuscript writing and figure generation, [missing], Analysis coordination, [missing], Integrated data analysis, [missing], scRNA-seq and snRNA-seq data generation and processing, [missing], ATAC-seq data generation and processing, [missing], Methylcytosine data production and analysis, [missing], Epi-retro-seq data generation and processing, [missing], ‘Omics data analysis, [missing], Tracing and connectivity data generation, [missing], Morphology data generation and reconstruction, [missing], OLST/STPT and other data generation, [missing], Morphology, connectivity and imaging analysis, [missing], Spatially resolved single-cell transcriptomics (MERFISH), [missing], Multimodal profiling (Patch-seq), [missing], Transgenic tools, [missing], NeMO archive and analytics, [missing], Brain Image Library (BIL) archive, [missing], DANDI archive, [missing], Brain Cell Data Center (BCDC), [missing], Project management, [missing], and BRAIN Initiative Cell Census Network (BICCN), [missing]

Subjects
Epigenomics, Male, INTERNEURONS, ORGANIZATION, MOUSE, Molecular neuroscience, Neural circuits, CLASSIFICATION, Article, Mice, Atlases as Topic, Glutamates, Species Specificity, Animals, Humans, TRANSCRIPTOMICS, SPECIFICATION, NEURONS, In Situ Hybridization, Fluorescence, Phylogeny, Neurons, Multidisciplinary, Gene Expression Profiling, Biology and Life Sciences, PATHWAYS, Brain, Callithrix, Censuses, Cellular neuroscience, Mathematics and Statistics, SINGLE, Organ Specificity, MORPHOLOGY, Motor cortex, Female, Single-Cell Analysis, Transcriptome
Abstract

Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties., The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Published
2021

15. A mesoscale connectome of the mouse brain

Author

Oh, Seung Wook, Harris, Julie A., Ng, Lydia, Winslow, Brent, Cain, Nicholas, Mihalas, Stefan, Wang, Quanxin, Lau, Chris, Kuan, Leonard, Henry, Alex M., Mortrud, Marty T., Ouellette, Benjamin, Nguyen, Thuc Nghi, Sorensen, Staci A., Slaughterbeck, Clifford R., Wakeman, Wayne, Li, Yang, Feng, David, Ho, Anh, Nicholas, Eric, Hirokawa, Karla E., Bohn, Phillip, Joines, Kevin M., Peng, Hanchuan, Hawrylycz, Michael J., Phillips, John W., Hohmann, John G., Wohnoutka, Paul, Gerfen, Charles R., Koch, Christof, Bernard, Amy, Dang, Chinh, Jones, Allan R., and Zeng, Hongkui

Subjects
Brain -- Research -- Physiological aspects, Neural circuitry -- Research -- Physiological aspects, Enhanced green fluorescent protein -- Research -- Physiological aspects, Computer simulation -- Usage, Computer-generated environments -- Usage, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease., A central principle of neuroscience is that the nervous system is a network of diverse types of neurons and supporting cells communicating with each other mainly through synaptic connections. This [...]

Published
2014
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16. A whole-brain monosynaptic input connectome to neuron classes in mouse visual cortex

Author

Yao, Shenqin, primary, Wang, Quanxin, additional, Hirokawa, Karla E., additional, Ouellette, Benjamin, additional, Ahmed, Ruweida, additional, Bomben, Jasmin, additional, Brouner, Krissy, additional, Casal, Linzy, additional, Caldejon, Shiella, additional, Cho, Andy, additional, Dotson, Nadezhda I., additional, Daigle, Tanya L., additional, Egdorf, Tom, additional, Enstrom, Rachel, additional, Gary, Amanda, additional, Gelfand, Emily, additional, Gorham, Melissa, additional, Griffin, Fiona, additional, Gu, Hong, additional, Hancock, Nicole, additional, Howard, Robert, additional, Kuan, Leonard, additional, Lambert, Sophie, additional, Lee, Eric Kenji, additional, Luviano, Jennifer, additional, Mace, Kyla, additional, Maxwell, Michelle, additional, Mortrud, Marty T., additional, Naeemi, Maitham, additional, Nayan, Chelsea, additional, Ngo, Nhan-Kiet, additional, Nguyen, Thuyanh, additional, North, Kat, additional, Ransford, Shea, additional, Ruiz, Augustin, additional, Seid, Sam, additional, Swapp, Jackie, additional, Taormina, Michael J, additional, Wakeman, Wayne, additional, Zhou, Thomas, additional, Nicovich, Philip R., additional, Williford, Ali, additional, Potekhina, Lydia, additional, McGraw, Medea, additional, Ng, Lydia, additional, Groblewski, Peter A., additional, Tasic, Bosiljka, additional, Mihalas, Stefan, additional, Harris, Julie A, additional, Cetin, Ali, additional, and Zeng, Hongkui, additional

Published
2021
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18. A mesoscale connectome of the mouse brain

Author

Wook Oh, Seung, Harris, Julie A., Ng, Lydia, Winslow, Brent, Cain, Nicholas, Mihalas, Stefan, Wang, Quanxin, Lau, Chris, Kuan, Leonard, Henry, Alex M., Mortrud, Marty T., Ouellette, Benjamin, Nghi Nguyen, Thuc, Sorensen, Staci A., Slaughterbeck, Clifford R., Wakeman, Wayne, Li, Yang, Feng, David, Ho, Anh, Nicholas, Eric, Hirokawa, Karla E., Bohn, Phillip, Joines, Kevin M., Peng, Hanchuan, Hawrylycz, Michael J., Phillips, John W., Hohmann, John G., Wohnoutka, Paul, Gerfen, Charles R., Koch, Christof, Bernard, Amy, Dang, Chinh, Jones, Allan R., and Zeng, Hongkui

Published
2014
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19. Regional, Layer, and Cell-Type-Specific Connectivity of the Mouse Default Mode Network

Author

Whitesell, Jennifer D., primary, Liska, Adam, additional, Coletta, Ludovico, additional, Hirokawa, Karla E., additional, Bohn, Phillip, additional, Williford, Ali, additional, Groblewski, Peter A., additional, Graddis, Nile, additional, Kuan, Leonard, additional, Knox, Joseph E., additional, Ho, Anh, additional, Wakeman, Wayne, additional, Nicovich, Philip R., additional, Nguyen, Thuc Nghi, additional, van Velthoven, Cindy T.J., additional, Garren, Emma, additional, Fong, Olivia, additional, Naeemi, Maitham, additional, Henry, Alex M., additional, Dee, Nick, additional, Smith, Kimberly A., additional, Levi, Boaz, additional, Feng, David, additional, Ng, Lydia, additional, Tasic, Bosiljka, additional, Zeng, Hongkui, additional, Mihalas, Stefan, additional, Gozzi, Alessandro, additional, and Harris, Julie A., additional

Published
2021
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20. Cellular Anatomy of the Mouse Primary Motor Cortex

Author

Muñoz-Castañeda, Rodrigo, primary, Zingg, Brian, additional, Matho, Katherine S., additional, Wang, Quanxin, additional, Chen, Xiaoyin, additional, Foster, Nicholas N., additional, Narasimhan, Arun, additional, Li, Anan, additional, Hirokawa, Karla E., additional, Huo, Bingxing, additional, Bannerjee, Samik, additional, Korobkova, Laura, additional, Park, Chris Sin, additional, Park, Young-Gyun, additional, Bienkowski, Michael S., additional, Chon, Uree, additional, Wheeler, Diek W., additional, Li, Xiangning, additional, Wang, Yun, additional, Kelly, Kathleen, additional, An, Xu, additional, Attili, Sarojini M., additional, Bowman, Ian, additional, Bludova, Anastasiia, additional, Cetin, Ali, additional, Ding, Liya, additional, Drewes, Rhonda, additional, D’Orazi, Florence, additional, Elowsky, Corey, additional, Fischer, Stephan, additional, Galbavy, William, additional, Gao, Lei, additional, Gillis, Jesse, additional, Groblewski, Peter A., additional, Gou, Lin, additional, Hahn, Joel D., additional, Hatfield, Joshua T., additional, Hintiryan, Houri, additional, Huang, Jason, additional, Kondo, Hideki, additional, Kuang, Xiuli, additional, Lesnar, Philip, additional, Li, Xu, additional, Li, Yaoyao, additional, Lin, Mengkuan, additional, Liu, Lijuan, additional, Lo, Darrick, additional, Mizrachi, Judith, additional, Mok, Stephanie, additional, Naeemi, Maitham, additional, Nicovich, Philip R., additional, Palaniswamy, Ramesh, additional, Palmer, Jason, additional, Qi, Xiaoli, additional, Shen, Elise, additional, Sun, Yu-Chi, additional, Tao, Huizhong, additional, Wakemen, Wayne, additional, Wang, Yimin, additional, Xie, Peng, additional, Yao, Shenqin, additional, Yuan, Jin, additional, Zhu, Muye, additional, Ng, Lydia, additional, Zhang, Li I., additional, Lim, Byung Kook, additional, Hawrylycz, Michael, additional, Gong, Hui, additional, Gee, James C., additional, Kim, Yongsoo, additional, Peng, Hanchuan, additional, Chuang, Kwanghun, additional, Yang, X William, additional, Luo, Qingming, additional, Mitra, Partha P., additional, Zador, Anthony M., additional, Zeng, Hongkui, additional, Ascoli, Giorgio A., additional, Huang, Z Josh, additional, Osten, Pavel, additional, Harris, Julie A., additional, and Dong, Hong-Wei, additional

Published
2020
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21. Regional, layer, and cell-class specific connectivity of the mouse default mode network

Author

Whitesell, Jennifer D., primary, Liska, Adam, additional, Coletta, Ludovico, additional, Hirokawa, Karla E., additional, Bohn, Phillip, additional, Williford, Ali, additional, Groblewski, Peter A., additional, Graddis, Nile, additional, Kuan, Leonard, additional, Knox, Joseph E., additional, Ho, Anh, additional, Wakeman, Wayne, additional, Nicovich, Philip R., additional, Nguyen, Thuc Nghi, additional, Garren, Emma, additional, van Velthoven, Cindy T. J., additional, Fong, Olivia, additional, Feng, David, additional, Naeemi, Maitham, additional, Henry, Alex M., additional, Dee, Nick, additional, Smith, Kimberly A., additional, Levi, Boaz P., additional, Ng, Lydia, additional, Tasic, Bosiljka, additional, Zeng, Hongkui, additional, Mihalas, Stefan, additional, Gozzi, Alessandro, additional, and Harris, Julie A., additional

Published
2020
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22. Distinct Transcriptomic Cell Types and Neural Circuits of the Subiculum and Prosubiculum along the Dorsal-Ventral Axis

Author

Ding, Song-Lin, primary, Yao, Zizhen, additional, Hirokawa, Karla E., additional, Nguyen, Thuc Nghi, additional, Graybuck, Lucas T., additional, Fong, Olivia, additional, Bohn, Phillip, additional, Ngo, Kiet, additional, Smith, Kimberly A., additional, Koch, Christof, additional, Phillips, John W., additional, Lein, Ed S., additional, Harris, Julie A., additional, Tasic, Bosiljka, additional, and Zeng, Hongkui, additional

Published
2020
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23. The Allen Mouse Brain Common Coordinate Framework: A 3D Reference Atlas

Author

Wang, Quanxin, primary, Ding, Song-Lin, additional, Li, Yang, additional, Royall, Josh, additional, Feng, David, additional, Lesnar, Phil, additional, Graddis, Nile, additional, Naeemi, Maitham, additional, Facer, Benjamin, additional, Ho, Anh, additional, Dolbeare, Tim, additional, Blanchard, Brandon, additional, Dee, Nick, additional, Wakeman, Wayne, additional, Hirokawa, Karla E., additional, Szafer, Aaron, additional, Sunkin, Susan M., additional, Oh, Seung Wook, additional, Bernard, Amy, additional, Phillips, John W., additional, Hawrylycz, Michael, additional, Koch, Christof, additional, Zeng, Hongkui, additional, Harris, Julie A., additional, and Ng, Lydia, additional

Published
2020
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24. Complete single neuron reconstruction reveals morphological diversity in molecularly defined claustral and cortical neuron types

Author

Wang, Yun, Xie, Peng, Gong, Hui, Zhou, Zhi, Kuang, Xiuli, Wang, Yimin, Li, An-an, Li, Yaoyao, Liu, Lijuan, Veldman, Matthew B., Daigle, Tanya L., Hirokawa, Karla E., Qu, Lei, Lesnar, Phil, Jiang, Shengdian, Yu, Yang, Wakeman, Wayne, Zeng, Shaoqun, Li, Xiangning, Yuan, Jing, Nguyen, Thuc Nghi, Larsen, Rachael, Kebede, Sara, Song, Yuanyuan, Yin, Lulu, Zhao, Sujun, Feiner, Aaron, Shen, Elise, Hill, Chris, Wang, Quanxin, Mok, Stephanie, Sunkin, Susan M., Josh Huang, Z., Esposito, Luke, Yao, Zizhen, Hawrylycz, Michael J., Tasic, Bosiljka, Ng, Lydia, Sorensen, Staci A., William Yang, X., Harris, Julie A., Koch, Christof, Luo, Qingming, Peng, Hanchuan, and Zeng, Hongkui

Abstract

SUMMARY Ever since the seminal findings of Ramon y Cajal, dendritic and axonal morphology has been recognized as a defining feature of neuronal types and their connectivity. Yet our knowledge about the diversity of neuronal morphology, in particular its distant axonal projections, is still extremely limited. To systematically obtain single neuron full morphology on a brain-wide scale in mice, we established a pipeline that encompasses five major components: sparse labeling, whole-brain imaging, reconstruction, registration, and classification. We achieved sparse, robust and consistent fluorescent labeling of a wide range of neuronal types across the mouse brain in an efficient way by combining transgenic or viral Cre delivery with novel transgenic reporter lines, and generated a large set of high-resolution whole-brain fluorescent imaging datasets containing thousands of reconstructable neurons using the fluorescence micro-optical sectioning tomography (fMOST) system. We developed a set of software tools based on the visualization and analysis suite, Vaa3D, for large-volume image data processing and computation-assisted morphological reconstruction. In a proof-of-principle case, we reconstructed full morphologies of 96 neurons from the claustrum and cortex that belong to a single transcriptomically-defined neuronal subclass. We developed a data-driven clustering approach to classify them into multiple morphological and projection types, suggesting that these neurons work in a targeted and coordinated manner to process cortical information. Imaging data and the new computational reconstruction tools are publicly available to enable community-based efforts towards large-scale full morphology reconstruction of neurons throughout the entire mouse brain.

Published
2019
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25. Distinct transcriptomic cell types and neural circuits of the subiculum and prosubiculum along the dorsal-ventral axis

Author

Ding, Song-Lin, primary, Yao, Zizhen, additional, Hirokawa, Karla E., additional, Nguyen, Thuc Nghi, additional, Graybuck, Lucas T., additional, Fong, Olivia, additional, Bohn, Phillip, additional, Ngo, Kiet, additional, Smith, Kimberly A., additional, Koch, Christof, additional, Phillips, John W., additional, Lein, Ed S., additional, Harris, Julie A., additional, Tasic, Bosiljka, additional, and Zeng, Hongkui, additional

Published
2019
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26. Brain-wide single neuron reconstruction reveals morphological diversity in molecularly defined striatal, thalamic, cortical and claustral neuron types

Author

Peng, Hanchuan, primary, Xie, Peng, additional, Liu, Lijuan, additional, Kuang, Xiuli, additional, Wang, Yimin, additional, Qu, Lei, additional, Gong, Hui, additional, Jiang, Shengdian, additional, Li, Anan, additional, Ruan, Zongcai, additional, Ding, Liya, additional, Chen, Chao, additional, Chen, Mengya, additional, Daigle, Tanya L., additional, Ding, Zhangcan, additional, Duan, Yanjun, additional, Feiner, Aaron, additional, He, Ping, additional, Hill, Chris, additional, Hirokawa, Karla E., additional, Hong, Guodong, additional, Huang, Lei, additional, Kebede, Sara, additional, Kuo, Hsien-Chi, additional, Larsen, Rachael, additional, Lesnar, Phil, additional, Li, Longfei, additional, Li, Qi, additional, Li, Xiangning, additional, Li, Yaoyao, additional, Li, Yuanyuan, additional, Liu, An, additional, Lu, Donghuan, additional, Mok, Stephanie, additional, Ng, Lydia, additional, Nguyen, Thuc Nghi, additional, Ouyang, Qiang, additional, Pan, Jintao, additional, Shen, Elise, additional, Song, Yuanyuan, additional, Sunkin, Susan M., additional, Tasic, Bosiljka, additional, Veldman, Matthew B., additional, Wakeman, Wayne, additional, Wan, Wan, additional, Wang, Peng, additional, Wang, Quanxin, additional, Wang, Tao, additional, Wang, Yaping, additional, Xiong, Feng, additional, Xiong, Wei, additional, Xu, Wenjie, additional, Yao, Zizhen, additional, Ye, Min, additional, Yin, Lulu, additional, Yu, Yang, additional, Yuan, Jia, additional, Yuan, Jing, additional, Yun, Zhixi, additional, Zeng, Shaoqun, additional, Zhang, Shichen, additional, Zhao, Sujun, additional, Zhao, Zijun, additional, Zhou, Zhi, additional, Huang, Z. Josh, additional, Esposito, Luke, additional, Hawrylycz, Michael J., additional, Sorensen, Staci A., additional, Yang, X. William, additional, Zheng, Yefeng, additional, Gu, Zhongze, additional, Xie, Wei, additional, Koch, Christof, additional, Luo, Qingming, additional, Harris, Julie A., additional, Wang, Yun, additional, and Zeng, Hongkui, additional

Published
2019
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27. Complete Whole-Brain Single Neuron Reconstruction Reveals Morphological Diversity in Molecularly Defined Claustral and Cortical Neuron Types

Author

Wang, Yun, primary, Xie, Peng, additional, Gong, Hui, additional, Zhou, Zhi, additional, Kuang, Xiuli, additional, Wang, Yimin, additional, Li, Anan, additional, Li, Yaoyao, additional, Liu, Lijuan, additional, Veldman, Matthew B., additional, Daigle, Tanya L., additional, Hirokawa, Karla E., additional, Qu, Lei, additional, Lesnar, Philip, additional, Jiang, Shengdian, additional, Yu, Yang, additional, Wakeman, Wayne, additional, Zeng, Shaoqun, additional, Li, Xiangning, additional, Yuan, Jing, additional, Nguyen, Thuc Nghi, additional, Larsen, Rachael, additional, Kebede, Sara, additional, Song, Yuanyuan, additional, Ying, Lulu, additional, Zhao, Sujun, additional, Feiner, Aaron, additional, Shen, Elise, additional, Hill, Chris, additional, Wang, Quanxin, additional, Mok, Stephanie, additional, Sunkin, Susan M., additional, Huang, Z. Josh, additional, Esposito, Luke, additional, Yao, Zizhen, additional, Hawrylycz, Michael J., additional, Tasic, Bosiljka, additional, Ng, Lydia, additional, Sorensen, Staci A., additional, Yang, X. William, additional, Harris, Julie A., additional, Koch, Christof, additional, Luo, Qingming, additional, Peng, Hanchuan, additional, and Zeng, Hongkui, additional

Published
2019
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28. Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease

Author

Whitesell, Jennifer D., primary, Buckley, Alex R., additional, Knox, Joseph E., additional, Kuan, Leonard, additional, Graddis, Nile, additional, Pelos, Andrew, additional, Mukora, Alice, additional, Wakeman, Wayne, additional, Bohn, Phillip, additional, Ho, Anh, additional, Hirokawa, Karla E., additional, and Harris, Julie A., additional

Published
2018
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29. A Suite of Transgenic Driver and Reporter Mouse Lines with Enhanced Brain-Cell-Type Targeting and Functionality

Author

Daigle, Tanya L., primary, Madisen, Linda, additional, Hage, Travis A., additional, Valley, Matthew T., additional, Knoblich, Ulf, additional, Larsen, Rylan S., additional, Takeno, Marc M., additional, Huang, Lawrence, additional, Gu, Hong, additional, Larsen, Rachael, additional, Mills, Maya, additional, Bosma-Moody, Alice, additional, Siverts, La’ Akea, additional, Walker, Miranda, additional, Graybuck, Lucas T., additional, Yao, Zizhen, additional, Fong, Olivia, additional, Nguyen, Thuc Nghi, additional, Garren, Emma, additional, Lenz, Garreck H., additional, Chavarha, Mariya, additional, Pendergraft, Julie, additional, Harrington, James, additional, Hirokawa, Karla E., additional, Harris, Julie A., additional, Nicovich, Philip R., additional, McGraw, Medea J., additional, Ollerenshaw, Douglas R., additional, Smith, Kimberly A., additional, Baker, Christopher A., additional, Ting, Jonathan T., additional, Sunkin, Susan M., additional, Lecoq, Jérôme, additional, Lin, Michael Z., additional, Boyden, Edward S., additional, Murphy, Gabe J., additional, da Costa, Nuno M., additional, Waters, Jack, additional, Li, Lu, additional, Tasic, Bosiljka, additional, and Zeng, Hongkui, additional

Published
2018
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30. The organization of intracortical connections by layer and cell class in the mouse brain

Author

Harris, Julie A., primary, Mihalas, Stefan, additional, Hirokawa, Karla E., additional, Whitesell, Jennifer D., additional, Knox, Joseph E., additional, Bernard, Amy, additional, Bohn, Phillip, additional, Caldejon, Shiella, additional, Casal, Linzy, additional, Cho, Andrew, additional, Feng, David, additional, Gaudreault, Nathalie, additional, Gerfen, Charles R., additional, Graddis, Nile, additional, Groblewski, Peter A., additional, Henry, Alex, additional, Ho, Anh, additional, Howard, Robert, additional, Kuan, Leonard, additional, Lecoq, Jerome, additional, Luviano, Jennifer, additional, McConoghy, Stephen, additional, Mortrud, Marty T., additional, Naeemi, Maitham, additional, Ng, Lydia, additional, Oh, Seung W., additional, Ouellette, Benjamin, additional, Sorensen, Staci A., additional, Wakeman, Wayne, additional, Wang, Quanxin, additional, Williford, Ali, additional, Phillips, John W., additional, Jones, Allan, additional, Koch, Christof, additional, and Zeng, Hongkui, additional

Published
2018
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31. Shared and distinct transcriptomic cell types across neocortical areas

Author

Tasic, Bosiljka, primary, Yao, Zizhen, additional, Smith, Kimberly A., additional, Graybuck, Lucas, additional, Nguyen, Thuc Nghi, additional, Bertagnolli, Darren, additional, Goldy, Jeff, additional, Garren, Emma, additional, Economo, Michael N., additional, Viswanathan, Sarada, additional, Penn, Osnat, additional, Bakken, Trygve, additional, Menon, Vilas, additional, Miller, Jeremy, additional, Fong, Olivia, additional, Hirokawa, Karla E., additional, Lathia, Kanan, additional, Rimorin, Christine, additional, Tieu, Michael, additional, Larsen, Rachael, additional, Casper, Tamara, additional, Barkan, Eliza, additional, Kroll, Matthew, additional, Parry, Seana, additional, Shapovalova, Nadiya V., additional, Hirchstein, Daniel, additional, Pendergraft, Julie, additional, Kim, Tae Kyung, additional, Szafer, Aaron, additional, Dee, Nick, additional, Groblewski, Peter, additional, Wickersham, Ian, additional, Cetin, Ali, additional, Harris, Julie A., additional, Levi, Boaz P., additional, Sunkin, Susan M, additional, Madisen, Linda, additional, Daigle, Tanya L., additional, Looger, Loren, additional, Bernard, Amy, additional, Phillips, John, additional, Lein, Ed, additional, Hawrylycz, Michael, additional, Svoboda, Karel, additional, Jones, Allan R., additional, Koch, Christof, additional, and Zeng, Hongkui, additional

Published
2017
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32. A suite of transgenic driver and reporter mouse lines with enhanced brain cell type targeting and functionality

Author

Daigle, Tanya L., primary, Madisen, Linda, additional, Hage, Travis A., additional, Valley, Matthew T., additional, Knoblich, Ulf, additional, Larsen, Rylan S., additional, Takeno, Marc M., additional, Huang, Lawrence, additional, Gu, Hong, additional, Larsen, Rachael, additional, Mills, Maya, additional, Bosma-Moody, Alice, additional, Siverts, La’Akea, additional, Walker, Miranda, additional, Graybuck, Lucas T., additional, Yao, Zizhen, additional, Fong, Olivia, additional, Garren, Emma, additional, Lenz, Garreck, additional, Chavarha, Mariya, additional, Pendergraft, Julie, additional, Harrington, James, additional, Hirokawa, Karla E., additional, Harris, Julie A., additional, McGraw, Medea, additional, Ollerenshaw, Douglas R., additional, Smith, Kimberly, additional, Baker, Christopher A., additional, Ting, Jonathan T., additional, Sunkin, Susan M., additional, Lecoq, Jerome, additional, Lin, Michael Z., additional, Boyden, Edward S., additional, Murphy, Gabe J., additional, da Costa, Nuno, additional, Waters, Jack, additional, Li, Lu, additional, Tasic, Bosiljka, additional, and Zeng, Hongkui, additional

Published
2017
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33. Diverse Central Projection Patterns of Retinal Ganglion Cells

Author

Martersteck, Emily M., primary, Hirokawa, Karla E., additional, Evarts, Mariah, additional, Bernard, Amy, additional, Duan, Xin, additional, Li, Yang, additional, Ng, Lydia, additional, Oh, Seung W., additional, Ouellette, Benjamin, additional, Royall, Joshua J., additional, Stoecklin, Michelle, additional, Wang, Quanxin, additional, Zeng, Hongkui, additional, Sanes, Joshua R., additional, and Harris, Julie A., additional

Published
2017
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34. Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease.

Author

Whitesell, Jennifer D., Buckley, Alex R., Knox, Joseph E., Kuan, Leonard, Graddis, Nile, Pelos, Andrew, Mukora, Alice, Wakeman, Wayne, Bohn, Phillip, Ho, Anh, Hirokawa, Karla E., and Harris, Julie A.

Abstract

A variety of Alzheimer's disease (AD) mouse models overexpress mutant forms of human amyloid precursor protein (APP), producing high levels of amyloid β (Aβ) and forming plaques. However, the degree to which these models mimic spatiotemporal patterns of Aβ deposition in brains of AD patients is unknown. Here, we mapped the spatial distribution of Aβ plaques across age in three APP‐overexpression mouse lines (APP/PS1, Tg2576, and hAPP‐J20) using in vivo labeling with methoxy‐X04, high throughput whole brain imaging, and an automated informatics pipeline. Images were acquired with high resolution serial two‐photon tomography and labeled plaques were detected using custom‐built segmentation algorithms. Image series were registered to the Allen Mouse Brain Common Coordinate Framework, a 3D reference atlas, enabling automated brain‐wide quantification of plaque density, number, and location. In both APP/PS1 and Tg2576 mice, plaques were identified first in isocortex, followed by olfactory, hippocampal, and cortical subplate areas. In hAPP‐J20 mice, plaque density was highest in hippocampal areas, followed by isocortex, with little to no involvement of olfactory or cortical subplate areas. Within the major brain divisions, distinct regions were identified with high (or low) plaque accumulation; for example, the lateral visual area within the isocortex of APP/PS1 mice had relatively higher plaque density compared with other cortical areas, while in hAPP‐J20 mice, plaques were densest in the ventral retrosplenial cortex. In summary, we show how whole brain imaging of amyloid pathology in mice reveals the extent to which a given model recapitulates the regional Aβ deposition patterns described in AD. [ABSTRACT FROM AUTHOR]

Published
2019
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35. Anatomical characterization of Cre driver mice for neural circuit mapping and manipulation

Author

Harris, Julie A., primary, Hirokawa, Karla E., additional, Sorensen, Staci A., additional, Gu, Hong, additional, Mills, Maya, additional, Ng, Lydia L., additional, Bohn, Phillip, additional, Mortrud, Marty, additional, Ouellette, Benjamin, additional, Kidney, Jolene, additional, Smith, Kimberly A., additional, Dang, Chinh, additional, Sunkin, Susan, additional, Bernard, Amy, additional, Oh, Seung Wook, additional, Madisen, Linda, additional, and Zeng, Hongkui, additional

Published
2014
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38. Lhx2 links the intrinsic and extrinsic factors that control optic cup formation.

Author

Sanghee Yun, Yukio Saijoh, Hirokawa, Karla E., Kopinke, Daniel, Murtaugh, L. Charles, Monuki, Edwin S., and Levine, Edward M.

Subjects
OCULAR tumors, MORPHOGENESIS, TRANSCRIPTION factors, HOMEOBOX genes, GENE expression, GENETIC regulation
Abstract

A crucial step in eye organogenesis is the transition of the optic vesicle into the optic cup. Several transcription factors and extracellular signals mediate this transition, but whether a single factor links them into a common genetic network is unclear. Here, we provide evidence that the LIM homeobox gene Lhx2, which is expressed in the optic neuroepithelium, fulfils such a role. In Lhx2-/- mouse embryos, eye field specification and optic vesicle morphogenesis occur, but development arrests prior to optic cup formation in both the optic neuroepithelium and lens ectoderm. This is accompanied by failure to maintain or initiate the expression patterns of optic-vesicle-patterning and lens-inducing determinants. Of the signaling pathways examined, only BMP signaling is noticeably altered and Bmp4 and Bmp7 mRNAs are undetectable. Lhx2-/- optic vesicles and lens ectoderm upregulate Pax2, Fgf15 and Sox2 in response to BMP treatments, and Lhx2 genetic mosaics reveal that transcription factors, including Vsx2 and Mitf, require Lhx2 cell-autonomously for their expression. Our data indicate that Lhx2 is required for optic vesicle patterning and lens formation in part by regulating BMP signaling in an autocrine manner in the optic neuroepithelium and in a paracrine manner in the lens ectoderm. We propose a model in which Lhx2 is a central link in a genetic network that coordinates the multiple pathways leading to optic cup formation. [ABSTRACT FROM AUTHOR]

Published
2009
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39. Modeling the cell-type-specific mesoscale murine connectome with anterograde tracing experiments.

Author

Koelle S, Mastrovito D, Whitesell JD, Hirokawa KE, Zeng H, Meila M, Harris JA, and Mihalas S

Abstract

The Allen Mouse Brain Connectivity Atlas consists of anterograde tracing experiments targeting diverse structures and classes of projecting neurons. Beyond regional anterograde tracing done in C57BL/6 wild-type mice, a large fraction of experiments are performed using transgenic Cre-lines. This allows access to cell-class-specific whole-brain connectivity information, with class defined by the transgenic lines. However, even though the number of experiments is large, it does not come close to covering all existing cell classes in every area where they exist. Here, we study how much we can fill in these gaps and estimate the cell-class-specific connectivity function given the simplifying assumptions that nearby voxels have smoothly varying projections, but that these projection tensors can change sharply depending on the region and class of the projecting cells. This paper describes the conversion of Cre-line tracer experiments into class-specific connectivity matrices representing the connection strengths between source and target structures. We introduce and validate a novel statistical model for creation of connectivity matrices. We extend the Nadaraya-Watson kernel learning method that we previously used to fill in spatial gaps to also fill in gaps in cell-class connectivity information. To do this, we construct a "cell-class space" based on class-specific averaged regionalized projections and combine smoothing in 3D space as well as in this abstract space to share information between similar neuron classes. Using this method, we construct a set of connectivity matrices using multiple levels of resolution at which discontinuities in connectivity are assumed. We show that the connectivities obtained from this model display expected cell-type- and structure-specific connectivities. We also show that the wild-type connectivity matrix can be factored using a sparse set of factors, and analyze the informativeness of this latent variable model., Competing Interests: Competing Interests: The authors have declared that no competing interests exist., (© 2023 Massachusetts Institute of Technology.)

Published
2023
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40. Connecting single-cell transcriptomes to projectomes in mouse visual cortex.

Author

Sorensen SA, Gouwens NW, Wang Y, Mallory M, Budzillo A, Dalley R, Lee B, Gliko O, Kuo HC, Kuang X, Mann R, Ahmadinia L, Alfiler L, Baftizadeh F, Baker K, Bannick S, Bertagnolli D, Bickley K, Bohn P, Brown D, Bomben J, Brouner K, Chen C, Chen K, Chvilicek M, Collman F, Daigle T, Dawes T, de Frates R, Dee N, DePartee M, Egdorf T, El-Hifnawi L, Enstrom R, Esposito L, Farrell C, Gala R, Glomb A, Gamlin C, Gary A, Goldy J, Gu H, Hadley K, Hawrylycz M, Henry A, Hill D, Hirokawa KE, Huang Z, Johnson K, Juneau Z, Kebede S, Kim L, Lee C, Lesnar P, Li A, Glomb A, Li Y, Liang E, Link K, Maxwell M, McGraw M, McMillen DA, Mukora A, Ng L, Ochoa T, Oldre A, Park D, Pom CA, Popovich Z, Potekhina L, Rajanbabu R, Ransford S, Reding M, Ruiz A, Sandman D, Siverts L, Smith KA, Stoecklin M, Sulc J, Tieu M, Ting J, Trinh J, Vargas S, Vumbaco D, Walker M, Wang M, Wanner A, Waters J, Williams G, Wilson J, Xiong W, Lein E, Berg J, Kalmbach B, Yao S, Gong H, Luo Q, Ng L, Sümbül U, Jarsky T, Yao Z, Tasic B, and Zeng H

Abstract

The mammalian brain is composed of diverse neuron types that play different functional roles. Recent single-cell RNA sequencing approaches have led to a whole brain taxonomy of transcriptomically-defined cell types, yet cell type definitions that include multiple cellular properties can offer additional insights into a neuron's role in brain circuits. While the Patch-seq method can investigate how transcriptomic properties relate to the local morphological and electrophysiological properties of cell types, linking transcriptomic identities to long-range projections is a major unresolved challenge. To address this, we collected coordinated Patch-seq and whole brain morphology data sets of excitatory neurons in mouse visual cortex. From the Patch-seq data, we defined 16 integrated morpho-electric-transcriptomic (MET)-types; in parallel, we reconstructed the complete morphologies of 300 neurons. We unified the two data sets with a multi-step classifier, to integrate cell type assignments and interrogate cross-modality relationships. We find that transcriptomic variations within and across MET-types correspond with morphological and electrophysiological phenotypes. In addition, this variation, along with the anatomical location of the cell, can be used to predict the projection targets of individual neurons. We also shed new light on infragranular cell types and circuits, including cell-type-specific, interhemispheric projections. With this approach, we establish a comprehensive, integrated taxonomy of excitatory neuron types in mouse visual cortex and create a system for integrated, high-dimensional cell type classification that can be extended to the whole brain and potentially across species.

Published
2023
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