Digital Atlasing and Standardization in the Mouse Brain

Hawrylycz, Michael; Baldock, Richard; Burger, Albert; Hashikawa, Tsutomu; Johnson, G. Allan; Martone, Maryann E.; Ng, Lydia; C, Lau; Larsen, Stephen D.; Nissanov, Jonathan; Puelles, Luis; Ruffins, Seth; Verbeek, Fons J.; Zaslavsky, Ilya; Boline, Jyl

doi:10.1371/journal.pcbi.1001065

Cited by 95 publications

(110 citation statements)

References 36 publications

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“…113,169 Zebrafish display a welldeveloped neuroendocrine system 74,170 and show high sensitivity of their CNS proto-oncogene expression to various experimental manipulations. 87,144,171 From this point of view, the sensitivity of zebrafish physiological biomarkers to hallucinogenic drugs (Table 2) supports the utility of such aquatic models to parallel behavioral phenotypes with physiological responses.…”

Section: ■ Modeling Hallucinogenic Drug Action In Zebrafishmentioning

confidence: 70%

Perspectives on Zebrafish Models of Hallucinogenic Drugs and Related Psychotropic Compounds

Neelkantan

Mikhaylova

Stewart

et al. 2013

ACS Chem. Neurosci.

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Among different classes of psychotropic drugs, hallucinogenic agents exert one of the most prominent effects on human and animal behaviors, markedly altering sensory, motor, affective, and cognitive responses. The growing clinical and preclinical interest in psychedelic, dissociative, and deliriant hallucinogens necessitates novel translational, sensitive, and high-throughput in vivo models and screens. Primate and rodent models have been traditionally used to study cellular mechanisms and neural circuits of hallucinogenic drugs' action. The utility of zebrafish (Danio rerio) in neuroscience research is rapidly growing due to their high physiological and genetic homology to humans, ease of genetic manipulation, robust behaviors, and cost effectiveness. Possessing a fully characterized genome, both adult and larval zebrafish are currently widely used for in vivo screening of various psychotropic compounds, including hallucinogens and related drugs. Recognizing the growing importance of hallucinogens in biological psychiatry, here we discuss hallucinogenic-induced phenotypes in zebrafish and evaluate their potential as efficient preclinical models of drug-induced states in humans.

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Section: ■ Modeling Hallucinogenic Drug Action In Zebrafishmentioning

confidence: 70%

Perspectives on Zebrafish Models of Hallucinogenic Drugs and Related Psychotropic Compounds

Neelkantan

Mikhaylova

Stewart

et al. 2013

ACS Chem. Neurosci.

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“…neuroscience | bioinformatics | neuroanatomy B rain-wide and genome-wide maps of gene expression are now available (1,2), due to the development of high-throughput neuroanatomical methods (3)(4)(5)(6). This has enabled analysis of the spatial correlation structure of gene expression (7)(8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

Cell-type–based model explaining coexpression patterns of genes in the brain

Grange

Bohland

Okaty

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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125

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Spatial patterns of gene expression in the vertebrate brain are not independent, as pairs of genes can exhibit complex patterns of coexpression. Two genes may be similarly expressed in one region, but differentially expressed in other regions. These correlations have been studied quantitatively, particularly for the Allen Atlas of the adult mouse brain, but their biological meaning remains obscure. We propose a simple model of the coexpression patterns in terms of spatial distributions of underlying cell types and establish its plausibility using independently measured cell-typespecific transcriptomes. The model allows us to predict the spatial distribution of cell types in the mouse brain.neuroscience | bioinformatics | neuroanatomy B rain-wide and genome-wide maps of gene expression are now available (1, 2), due to the development of high-throughput neuroanatomical methods (3-6). This has enabled analysis of the spatial correlation structure of gene expression (7-12). In the Allen Brain Atlas (ABA) of the adult mouse, the brain is divided up into cubic voxels of size 200 μm. The expression energies of up to 20,000 genes in the adult C57BL/6J mouse are given by automatic processing of in situ hybridized (ISH) brain sections, coregistered to the Allen Reference Atlas (ARA) (13). Coexpression of two genes in a voxel may arise from two sources: ðiÞ both genes are expressed within the same cell type or ðiiÞ the two genes are expressed in two different cell types, both present in the voxel. These two possibilities cannot be disentangled solely on the basis of the ABA. Ideally, gene expression profiles should be experimentally obtained for each cell type in the brain, and indeed such transcriptome profiles are now available (14-21). This cell-based approach to the study of gene expression is complementary to the gene-based approach of the ABA. In ref. 22, the data of ref. 19 were used to extract neuron-specific genes, astrocyte-specific genes, and oligodendrocyte-specific genes, which resulted in three combinations of brain-wide maps from the ABA, whose clustering showed anatomical signatures of major brain subdivisions (see also ref. 23 for estimates of neuron-specific and oligodendrocyte-specific expression patterns, both in the mouse and in the human brain). The present paper goes beyond the broad classification of cell types into three classes and attempts to estimate density profiles of every cell type known by its transcriptome profile. To study the genes collectively we use a voxel-by-gene data matrix E, corresponding to V = 49;742 cubic voxels, and 3,041 genes, as in refs. 24-26. The entry Eðv; gÞ is the expression energy of the gene labeled g in the voxel labeled v [a measure representing the level of mRNA in situ hybridization (1, 10)]. We combine the ABA with cell-type-specific transcriptome profiles, to gain biological understanding of the coexpression patterns of the genes. Our model is based on G = 2;131 genes found in all these datasets and in the coronal ABA. The model proposed to estimate the brain-w...

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“…Another approach to combine and integrate various neuroanatomical data is to use a common reference space (Bjaalie, 2002;Hawrylycz et al, 2011). In their contribution to this Research Topic, Ropireddy and Ascoli (2011) demonstrate how potential connections (defined by close apposition of axonal and dendritic segments) can be inferred from a collection of detailed 3-D reconstructions of neuronal extensions that were accumulated in a common 3-D reconstruction of the rat hippocampus on the basis of positional values ( Figure 1J).…”

Section: Background and Scopementioning

confidence: 99%

Mapping the connectome: Multi-level analysis of brain connectivity

2013

Frontiers Research Topics

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Digital Atlasing and Standardization in the Mouse Brain

Cited by 95 publications

References 36 publications

Perspectives on Zebrafish Models of Hallucinogenic Drugs and Related Psychotropic Compounds

Perspectives on Zebrafish Models of Hallucinogenic Drugs and Related Psychotropic Compounds

Cell-type–based model explaining coexpression patterns of genes in the brain

Mapping the connectome: Multi-level analysis of brain connectivity

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