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1. Survey of spiking in the mouse visual system reveals functional hierarchy

Author

Luke Esposito, John W. Phillips, Lydia Ng, Maggie Chvilicek, Kara Ronellenfitch, Corbett Bennett, Kael Dai, Peter A. Groblewski, John Galbraith, Jackie Swapp, Brian Hu, Ross Hytnen, Fuhui Long, Emily Gelfand, R.D. Young, India Kato, Linzy Casal, Greggory Heller, Jennifer Luviano, Xiaoxuan Jia, Ben Sutton, Michael A. Buice, Saskia E. J. de Vries, Shiella Caldejon, Sam Seid, Tamina K. Ramirez, Thuyahn Nguyen, Wayne Wakeman, Chelsea Nayan, Philip R. Nicovich, Roald Dietzman, Nicole Hancock, Colin Farrell, Carol L. Thompson, David Feng, Erika Jessett, Hongkui Zeng, Elizabeth Liang, Shawn R. Olsen, Kristen Turner, Jérôme Lecoq, Derric Williams, Katelyn Johnson, Jose Melchior, Stefan Mihalas, Hannah Choi, Sam Gale, Jennifer D. Whitesell, Ramakrishnan Iyer, Kat North, Melissa Reding, Dillan Brown, Yang Li, Kiet Ngo, Séverine Durand, Robert Howard, Amy Bernard, Anton Arkhipov, Julie A. Harris, Ali Williford, Yazan N. Billeh, Marina Garrett, Sophie Lambert, Tyler Mollenkopf, Arielle Leon, Marius Pachitariu, Michael Oliver, Nicolas Cain, Gabriel Koch Ocker, Daniel J. Denman, Justin T. Kiggins, Joshua H. Siegle, R. Clay Reid, Douglas R. Ollerenshaw, David Reid, Cliff Slaughterbeck, David Sullivan, Jed Perkins, Ruweida Ahmed, Daniel Millman, Jung Hoon Lee, Kyla Mace, Christof Koch, Andrew Cho, Nile Graddis, Timothy C. Cox, Peter Ledochowitsch, Miranda Robertson, Michelle Stoecklin, and Sarah A. Naylor

Subjects
0301 basic medicine, Hierarchy, Retina, Multidisciplinary, Neocortex, Visual perception, genetic structures, Computer science, Direct observation, Visual task, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, medicine, Latency (engineering), Neuroscience, 030217 neurology & neurosurgery, Coding (social sciences)
Abstract

The anatomy of the mammalian visual system, from the retina to the neocortex, is organized hierarchically1. However, direct observation of cellular-level functional interactions across this hierarchy is lacking due to the challenge of simultaneously recording activity across numerous regions. Here we describe a large, open dataset-part of the Allen Brain Observatory2-that surveys spiking from tens of thousands of units in six cortical and two thalamic regions in the brains of mice responding to a battery of visual stimuli. Using cross-correlation analysis, we reveal that the organization of inter-area functional connectivity during visual stimulation mirrors the anatomical hierarchy from the Allen Mouse Brain Connectivity Atlas3. We find that four classical hierarchical measures-response latency, receptive-field size, phase-locking to drifting gratings and response decay timescale-are all correlated with the hierarchy. Moreover, recordings obtained during a visual task reveal that the correlation between neural activity and behavioural choice also increases along the hierarchy. Our study provides a foundation for understanding coding and signal propagation across hierarchically organized cortical and thalamic visual areas.

Published
2021
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2. Survey of spiking in the mouse visual system reveals functional hierarchy

Author

Joshua H, Siegle, Xiaoxuan, Jia, Séverine, Durand, Sam, Gale, Corbett, Bennett, Nile, Graddis, Greggory, Heller, Tamina K, Ramirez, Hannah, Choi, Jennifer A, Luviano, Peter A, Groblewski, Ruweida, Ahmed, Anton, Arkhipov, Amy, Bernard, Yazan N, Billeh, Dillan, Brown, Michael A, Buice, Nicolas, Cain, Shiella, Caldejon, Linzy, Casal, Andrew, Cho, Maggie, Chvilicek, Timothy C, Cox, Kael, Dai, Daniel J, Denman, Saskia E J, de Vries, Roald, Dietzman, Luke, Esposito, Colin, Farrell, David, Feng, John, Galbraith, Marina, Garrett, Emily C, Gelfand, Nicole, Hancock, Julie A, Harris, Robert, Howard, Brian, Hu, Ross, Hytnen, Ramakrishnan, Iyer, Erika, Jessett, Katelyn, Johnson, India, Kato, Justin, Kiggins, Sophie, Lambert, Jerome, Lecoq, Peter, Ledochowitsch, Jung Hoon, Lee, Arielle, Leon, Yang, Li, Elizabeth, Liang, Fuhui, Long, Kyla, Mace, Jose, Melchior, Daniel, Millman, Tyler, Mollenkopf, Chelsea, Nayan, Lydia, Ng, Kiet, Ngo, Thuyahn, Nguyen, Philip R, Nicovich, Kat, North, Gabriel Koch, Ocker, Doug, Ollerenshaw, Michael, Oliver, Marius, Pachitariu, Jed, Perkins, Melissa, Reding, David, Reid, Miranda, Robertson, Kara, Ronellenfitch, Sam, Seid, Cliff, Slaughterbeck, Michelle, Stoecklin, David, Sullivan, Ben, Sutton, Jackie, Swapp, Carol, Thompson, Kristen, Turner, Wayne, Wakeman, Jennifer D, Whitesell, Derric, Williams, Ali, Williford, Rob, Young, Hongkui, Zeng, Sarah, Naylor, John W, Phillips, R Clay, Reid, Stefan, Mihalas, Shawn R, Olsen, and Christof, Koch

Subjects
Electrophysiology, Male, Mice, Inbred C57BL, Mice, Thalamus, Action Potentials, Animals, Datasets as Topic, Photic Stimulation, Visual Cortex
Abstract

The anatomy of the mammalian visual system, from the retina to the neocortex, is organized hierarchically

Published
2019

3. A survey of spiking activity reveals a functional hierarchy of mouse corticothalamic visual areas

Author

Jessett E, David Feng, Thuyanh V. Nguyen, Yazan N. Billeh, Sophie Lambert, Lindsay Ng, Michael A. Buice, Ramakrishnan Iyer, Chelsea Nayan, Brown D, Sutton B, R.D. Young, Stefan Mihalas, Ali Williford, Brian Hu, Kat North, Julie A. Harris, Greggory Heller, Nicole Hancock, Yang Li, Jérôme Lecoq, John W. Phillips, Emily Gelfand, Séverine Durand, Fuhui Long, Melchior J, Justin T. Kiggins, Kiet Ngo, Nicholas Cain, Sarah A. Naylor, Sam Seid, Karly M. Turner, Hannah Choi, Melissa Reding, John Galbraith, Jackie Swapp, India Kato, Colin Farrell, Johnson K, Joshua H. Siegle, Kara Ronellenfitch, Corbett Bennett, Mollenkopf Ts, Douglas R. Ollerenshaw, Marius Pachitariu, Chvilicek M, David Reid, Kael Dai, Timothy C. Cox, Peter A. Groblewski, Robert Reid, Philip R. Nicovich, Anton Arkhipov, Olsen, Samuel D. Gale, Hytnen R, Luke Esposito, Robert Howard, Jennifer D. Whitesell, Daniel J. Denman, Linzy Casal, Clifford R. Slaughterbeck, Cho A, Shiella Caldejon, Liang E, Xiaoxuan Jia, Tamina K. Ramirez, Wayne Wakeman, Jennifer Luviano, Derric Williams, Daniel Millman, Jung Hoon Lee, Hongkui Zeng, de Vries Sej, Christof Koch, Arielle Leon, Dietzman R, Amy Bernard, Marina Garrett, Carol L. Thompson, Gabriel Koch Ocker, Nile Graddis, Peter Ledochowitsch, Miranda Robertson, Michelle Stoecklin, Jed Perkins, Kyla Mace, Michael Oliver, David Sullivan, and Ruweida Ahmed

Subjects
Retina, Visual perception, medicine.anatomical_structure, Neocortex, genetic structures, Computer science, Receptive field, Functional connectivity, medicine, Stimulus (physiology), Neuroscience
Abstract

The mammalian visual system, from retina to neocortex, has been extensively studied at both anatomical and functional levels. Anatomy indicates the cortico-thalamic system is hierarchical, but characterization of cellular-level functional interactions across multiple levels of this hierarchy is lacking, partially due to the challenge of simultaneously recording activity across numerous regions. Here, we describe a large, open dataset (part of theAllen Brain Observatory) that surveys spiking from units in six cortical and two thalamic regions responding to a battery of visual stimuli. Using spike cross-correlation analysis, we find that inter-area functional connectivity mirrors the anatomical hierarchy from theAllen Mouse Brain Connectivity Atlas. Classical functional measures of hierarchy, including visual response latency, receptive field size, phase-locking to a drifting grating stimulus, and autocorrelation timescale are all correlated with the anatomical hierarchy. Moreover, recordings during a visual task support the behavioral relevance of hierarchical processing. Overall, this dataset and the hierarchy we describe provide a foundation for understanding coding and dynamics in the mouse cortico-thalamic visual system.

Published
2019
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4. A comprehensive transcriptional map of primate brain development

Author

Songlin Ding, R.D. Young, Paul Wohnoutka, Anna Hoerder-Suabedissen, Brian L. Youngstrom, Rachel A. Dalley, Terri L. Gilbert, Stephanie Butler, Lydia Potekhina, Jody Parente, Shiella Caldejon, Shu Shi, Kimberly A. Smith, Lon T. Luong, Chinh Dang, Aaron Oldre, Shelby Cate, Emi J. Byrnes, Susan M. Sunkin, Joshua J. Royall, Jefferey Chen, Amanda Ebbert, Jeffrey Rogers, Zeb Haradon, Lindsey Gourley, Ryan May, Naveed Mastan, Aaron Szafer, Chihchau L. Kuan, Kristopher Bickley, Tracy Lemon, Nick Dee, Nerick Mosqueda, Ed S. Lein, David Rosen, Mike Chapin, John W. Phillips, Guangyu Gu, Crissa Bennett, Nadia Dotson, Kate Roll, Ali Kriedberg, Nika Hejazinia, Nadiya V. Shapovalova, Brandon Rogers, Jon Hall, David G. Amaral, Robert Howard, Melaine Sarreal, Sheana Parry, Kaylynn Aiona, Tim A. Dolbeare, Michael Hawrylycz, Allan R. Jones, Robert F. Hevner, Nathan Sjoquist, Tyson Roberts, Marty Kinnunen, Lissette Velasquez, Jay Jochim, Richard A. Gibbs, Anita Carey, Tsega Desta, Jennifer Wu, Kiet Ngo, Julie Nyhus, Julie Pendergraft, Ben W. Gregor, Sheila Shapouri, Amy Bernard, Lydia Ng, Darren Bertagnolli, Eric Olson, Jeff Goldy, Udi Wagley, Changkyu Lee, Christopher Lau, David R. Haynor, Krissy Brouner, Erika Mott, Jeremy A. Miller, Andy J. Sodt, Jeffrey L. Bennett, Jose Melchor, Patrick D. Parker, Cassandra White, Zoltán Molnár, Andrew F. Boe, Zackery L. Riley, Trygve E. Bakken, David Sandman, Garrett Gee, James M. Arnold, Erich Fulfs, Robbie Townsend, Wayne Wakeman, John G. Hohmann, Felix Lee, and Melissa Reding

Subjects
0301 basic medicine, Male, Microcephaly, Aging, Transcription, Genetic, Autism Spectrum Disorder, Neocortex, Molecular neuroscience, Transcriptome, 0302 clinical medicine, Risk Factors, 2.1 Biological and endogenous factors, Primate, Conserved Sequence, Pediatric, Multidisciplinary, biology, Neurogenesis, Brain, Mental Health, medicine.anatomical_structure, Autism spectrum disorder, Neurological, Stem Cell Research - Nonembryonic - Non-Human, Female, Transcription, Biotechnology, General Science & Technology, Intellectual and Developmental Disabilities (IDD), 1.1 Normal biological development and functioning, Article, 03 medical and health sciences, Spatio-Temporal Analysis, Species Specificity, Genetic, biology.animal, Intellectual Disability, Genetics, medicine, Cell Adhesion, Animals, Humans, Cell projection, Human Genome, Neurosciences, Stem Cell Research, medicine.disease, Macaca mulatta, Brain Disorders, 030104 developmental biology, Neurodevelopmental Disorders, Schizophrenia, Neuroscience, 030217 neurology & neurosurgery
Abstract

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey.

Published
2016

5. An anatomic transcriptional atlas of human glioblastoma

Author

Greg Foltz, Parvinder Hothi, Ali Kriedberg, Krissy Brouner, David Feng, Chantal Murthy, Robert Howard, Robert C. Rostomily, David Sandman, Eric Olson, Nadezhda Dotson, Nameeta Shah, Guangyu Gu, Kris Bickley, Lydia Ng, Nika Hejazinia, John W. Phillips, Leonard Kuan, Charles Cobbs, Garrett Gee, Tim A. Dolbeare, Tsega Desta, Shiella Caldejon, Kiet Ngo, Haley Gittleman, Andrew F. Boe, Hwahyung Lee, Rachel A. Dalley, Steven J. White, Chris Lau, Bart Keogh, Graham Stockdale, Lindsey Gourley, Fuhui Long, Darren Bertagnolli, Andrew Sodt, Michael Hawrylycz, Amanda Ebbert, Jill S. Barnholtz-Sloan, David Rosen, Michael S. Fisher, Antonio Iavarone, Ed S. Lein, Stephanie Butler, Patrick J. Cimino, Tracy Lemon, Zack Riley, Allan R. Jones, Megha S Uppin, Mike Chapin, Naveed Mastan, Kimberly A. Smith, Michael E. Berens, Clifford R. Slaughterbeck, Aaron Szafer, Nick Dee, Wayne Wakeman, John G. Hohmann, Benjamin W. Gregor, Suvro Datta, Felix Lee, Ralph B. Puchalski, Melissa Reding, Nadiya V. Shapovalova, Xu Feng, Amy Bernard, Jae Guen Yoon, Erika Mott, Jeremy A. Miller, Justin D. Lathia, Steve R. Nomura, Steven Rostad, Kevin M. Joines, Paul Wohnoutka, Jeff Goldy, Don Marsh, Farrokh Farrokhi, Michael Lankerovich, C. Dirk Keene, and Chinh Dang

Subjects
0301 basic medicine, Poor prognosis, Multidisciplinary, Extramural, Brain Neoplasms, Gene Expression Profiling, Brain tumor, Computational biology, Biology, medicine.disease, Prognosis, Genomic databases, Data resources, Article, nervous system diseases, Gene expression profiling, 03 medical and health sciences, 030104 developmental biology, Atlases as Topic, Databases, Genetic, medicine, Humans, Glioblastoma, neoplasms
Abstract

Anatomically correct tumor genomics Glioblastoma is the most lethal form of human brain cancer. The genomic alterations and gene expression profiles characterizing this tumor type have been widely studied. Puchalski et al. created the Ivy Glioblastoma Atlas, a freely available online resource for the research community. The atlas, a collaborative effort between bioinformaticians and pathologists, maps molecular features of glioblastomas, such as transcriptional signatures, to histologically defined anatomical regions of the tumors. The relationships identified in this atlas, in conjunction with associated databases of clinical and genomic information, could provide new insights into the pathogenesis, diagnosis, and treatment of glioblastoma. Science , this issue p. 660

Published
2016

6. An anatomically comprehensive atlas of the adult human brain transcriptome

Author

Susan M. Sunkin, Preston M. Cartagena, Robert Howard, Christian F. Beckmann, David Feng, Zeb Haradon, Chinh Dang, Angela L. Guillozet-Bongaarts, Derric Williams, Jeff Goldy, Yang Li, Rachel A. Dalley, Tracy Lemon, Darren Bertagnolli, Clifford R. Slaughterbeck, Simon Smith, Steve Horvath, Christof Koch, Amanda Ebbert, Andreas Jeromin, Paul Wohnoutka, Michael Hawrylycz, Andy J. Sodt, Beryl Swanson, H. Ronald Zielke, Zackery L. Riley, John A. Morris, Evan T. Lazarz, Chris Abajian, Allan R. Jones, Mike Chapin, Changkyu Lee, Pedro Adolfo Sequeira, Jay Schulkin, Christopher Lau, Jeremy A. Miller, Tim A. Dolbeare, Ling Li, Nick Dee, Sheana Parry, Barry Daly, Patrick D. Parker, Marty Kinnunen, Amy Bernard, Joshua J. Royall, Vance Faber, John G. Hohmann, Patrick R. Hof, Stephen M. Smith, Suvro Datta, Kimberly A. Smith, Elaine H. Shen, Caroline C. Overly, Ed S. Lein, Jayson M. Jochim, Benjamin W. Gregor, Melissa Reding, M. Mallar Chakravarty, Seth G. N. Grant, Lydia Ng, Jimmy Chong, Marquis P. Vawter, Daniel H. Geschwind, David R. Haynor, Andrew F. Boe, Louie N. van de Lagemaat, David R. Fowler, Magnetic Detection and Imaging, and Faculty of Science and Technology

Subjects
Adult, Male, Cell type, Calbindins, Dopamine, Neocortex, Biology, Hippocampus, Article, Transcriptome, 03 medical and health sciences, Mice, METIS-292322, 0302 clinical medicine, Atlases as Topic, S100 Calcium Binding Protein G, Species Specificity, Databases, Genetic, Transcriptional regulation, medicine, Animals, Humans, RNA, Messenger, Anatomy, Artistic, In Situ Hybridization, 030304 developmental biology, Oligonucleotide Array Sequence Analysis, Genetics, 0303 health sciences, Internet, IR-83002, Multidisciplinary, Anatomical location, Gene Expression Profiling, Brain, Post-Synaptic Density, Human brain, Macaca mulatta, Gene expression profiling, medicine.anatomical_structure, Frontal lobe, Health, Neuroscience, 030217 neurology & neurosurgery
Abstract

Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ~900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography— the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.

Published
2012

7. Divergent and nonuniform gene expression patterns in mouse brain

Author

Tracy Lemon, Tsega Desta, Katie J. Glattfelder, Allan R. Jones, Beth M. Solan, Cathy Copeland, Andrew F. Boe, Jeff Goldy, Ed S. Lein, Chad Soden, Geralyn J. Orta, Michael Hawrylycz, John A. Morris, Darren Bertagnolli, John G. Hohmann, Shanna R. Fischer, Melissa Reding, Sheana Parry, Josh J. Burnell, Kimberly A. Smith, Caroline C. Overly, Jolene Kidney, Owen C. Pearson, Sayan Dev Pathak, Joseph S. Takahashi, Sheila Shapouri, John R. Weller, Emi J. Byrnes, and Joshua J. Royall

Subjects
Genetics, Regulation of gene expression, Multidisciplinary, Gene Expression Profiling, Laboratory mouse, Brain, Biological Sciences, Biology, Phenotype, Gene expression profiling, Mice, medicine.anatomical_structure, Gene Expression Regulation, Species Specificity, Gene expression, Expression quantitative trait loci, medicine, Animals, Humans, Gene, In Situ Hybridization, Neuroanatomy
Abstract

Considerable progress has been made in understanding variations in gene sequence and expression level associated with phenotype, yet how genetic diversity translates into complex phenotypic differences remains poorly understood. Here, we examine the relationship between genetic background and spatial patterns of gene expression across seven strains of mice, providing the most extensive cellular-resolution comparative analysis of gene expression in the mammalian brain to date. Using comprehensive brainwide anatomic coverage (more than 200 brain regions), we applied in situ hybridization to analyze the spatial expression patterns of 49 genes encoding well-known pharmaceutical drug targets. Remarkably, over 50% of the genes examined showed interstrain expression variation. In addition, the variability was nonuniformly distributed across strain and neuroanatomic region, suggesting certain organizing principles. First, the degree of expression variance among strains mirrors genealogic relationships. Second, expression pattern differences were concentrated in higher-order brain regions such as the cortex and hippocampus. Divergence in gene expression patterns across the brain could contribute significantly to variations in behavior and responses to neuroactive drugs in laboratory mouse strains and may help to explain individual differences in human responsiveness to neuroactive drugs.

Published
2010
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8. Transcriptional landscape of the prenatal human brain

Author

Amy Bernard, Phil Lesnar, Daniel H. Geschwind, Sheana Parry, Ed S. Lein, Benjamin W. Gregor, Theresa Naluai-Cecchini, John W. Phillips, Elaine H. Shen, Julie Nyhus, Chinh Dang, Rachel A. Dalley, Susan M. Sunkin, Nerick Mosqueda, Mark Gerstein, Lydia Ng, Hao Huang, Guangyu Gu, Lindsey Gourley, Tim A. Dolbeare, Darren Bertagnolli, Ian A. Glass, Bergen McMurray, Melaine Sarreal, Allison Stevens, Tim P. Fliss, Crissa Bennet, Clifford R. Slaughterbeck, Aaron Szafer, Mihovil Pletikos, Nenad Sestan, Benjamin A.C. Facer, Nick Dee, David Feng, Jody Parente, Paul Wohnoutka, Andy J. Sodt, Robert Howard, Christopher Lau, Tracy Lemon, Aaron Oldre, Robert F. Hevner, Nathan Sjoquist, Michael Hawrylycz, Nadiya V. Shapovalova, Joshua J. Royall, Pat Levitt, Zackery L. Riley, Anita Carey, John G. Hohmann, Kaylynn Aiona, Bruce Fischl, James A. Knowles, Felix Lee, Lilla Zöllei, Sheila Shapouri, Eric Olson, Melissa Reding, Christine Cuhaciyan, Shiella Caldejon, Songlin Ding, Derric Williams, Chihchau L. Kuan, Jayson M. Jochim, Michael W. Smith, Krissy Brouner, Allan R. Jones, Patrick D. Parker, Garrett Gee, Kate Roll, David Sandman, Stephanie Butler, James M. Arnold, Kimberly A. Smith, Jeremy A. Miller, Jeff Goldy, Nhan Kiet Ngo, Amanda Ebbert, Changkyu Lee, and Naveed Mastan

Subjects
Evolution, General Science & Technology, 1.1 Normal biological development and functioning, Neocortex, Biology, Human brain, Microarray, Development, Article, Transcriptome, Mice, Fetus, Atlases as Topic, Species Specificity, Stem Cell Research - Nonembryonic - Human, Underpinning research, Subplate, medicine, Genetics, Animals, Humans, Artistic, Developmental, Gene Regulatory Networks, Anatomy, Artistic, Conserved Sequence, Regulation of gene expression, Pediatric, Multidisciplinary, Microarray analysis techniques, Neurosciences, Gene Expression Regulation, Developmental, Brain, Stem Cell Research, Human Fetal Tissue, medicine.anatomical_structure, Frontal lobe, Gene Expression Regulation, Cerebral cortex, Neurological, Gene expression, Anatomy, Neuroscience, Biotechnology
Abstract

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.

Published
2014

9. Comprehensive cellular-resolution atlas of the adult human brain

Author

Aaron Szafer, Nick Dee, Paul Wohnoutka, Ani Varjabedian, John W. Phillips, Ed S. Lein, Bergen McMurray, Allison Stevens, Tim A. Dolbeare, Lee S. Tirrell, Susan M. Sunkin, Michael Hawrylycz, Shiella Caldejon, Patrick R. Hof, Christopher Lau, Elaine Shen, Christof Koch, John G. Hohmann, Joshua J. Royall, Lilla Zöllei, James A. Knowles, Phil Lesnar, Melissa Reding, Bruce Fischl, Songlin Ding, Benjamin A.C. Facer, Michelle Write, Lydia Ng, Chinh Dang, Julie Nyhus, Rachel A. Dalley, Allan R. Jones, Nenad Sestan, H. Ronald Zielke, Amy Bernard, Thomas Benner, Zackery L. Riley, David Sandman, Andre van der Kouwe, and Angie Guillozet-Bongaarts

Subjects
0301 basic medicine, cytoarchitecture, DWI, brainstem, 0302 clinical medicine, Neurofilament Proteins, SCR_014329, parvalbumin, Image Processing, Computer-Assisted, Anatomy, Artistic, hypothalamus, 0303 health sciences, medicine.diagnostic_test, General Neuroscience, Brain, amygdala, Human brain, Magnetic Resonance Imaging, brain atlas, Parvalbumins, medicine.anatomical_structure, Cytoarchitecture, Nissl body, symbols, cerebral cortex, Female, Erratum, Research Article, MRI, Adult, cerebellum, Biology, White matter, symbols.namesake, 03 medical and health sciences, hippocampal formation, Neuroimaging, thalamus, medicine, Humans, neurofilament protein, AB_2314904, 030304 developmental biology, Brain atlas, Brain morphometry, Magnetic resonance imaging, Diffusion Magnetic Resonance Imaging, 030104 developmental biology, RRIDs: AB_10000343, Neuroscience, 030217 neurology & neurosurgery
Abstract

Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Published
2016
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10. Comprehensive cellular-resolution atlas of the adult human brain

Author

H. Ronald Zielke, Michael Hawrylycz, Patrick R. Hof, Lydia Ng, Phil Lesnar, Thomas Benner, Bruce Fischl, Julie Nyhus, James A. Knowles, Allison Stevens, Christof Koch, David Sandman, Lee S. Tirrell, Songlin Ding, Ed S. Lein, Angie Guillozet-Bongaarts, Zackery L. Riley, Michelle Write, John W. Phillips, Joshua J. Royall, Aaron Szafer, John G. Hohmann, Nick Dee, Bergen McMurray, Benjamin A.C. Facer, Lilla Zöllei, Tim A. Dolbeare, Susan M. Sunkin, Amy Bernard, Melissa Reding, Elaine Shen, Shiella Caldejon, Allan R. Jones, Andre van der Kouwe, Paul Wohnoutka, Ani Varjabedian, Nenad Sestan, Christopher Lau, Chinh Dang, and Rachel A. Dalley

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Cellular resolution, Atlas (anatomy), General Neuroscience, medicine, Human brain, Biology, Neuroscience, 030217 neurology & neurosurgery
Published
2016
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