Database and tools for analysis of topographic organization and map transformations in major projection systems of the brain

Bjaalie, Jan G.; Leergaard, Trygve B.; Lillehaug, Sveinung; Odeh, Francis; Moene, Ivar; Kjode, J.O.; Darin, D.

doi:10.1016/j.neuroscience.2005.06.036

Cited by 25 publications

(27 citation statements)

References 70 publications

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“…In particular, punctate signal was detected at the location of basal pontine nuclei with a non-cellular pattern ( Figures 4D–F ). The distribution was similar to the one reported in the literature for cortico-pontine terminals using anterograde tracers (Bjaalie et al, 2005). EGFP immunoreactive terminals colocalized with the pan-vesicular marker synaptotagmin-1 (Syt-1, Figure 4 ).…”

Section: Resultssupporting

confidence: 87%

A conditional transgenic reporter of presynaptic terminals reveals novel features of the mouse corticospinal tract

D’Acunzo¹,

Badaloni²,

Ferro³

et al. 2014

Front. Neuroanat.

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In many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), synaptic alterations precede the demise of the neuronal cell, making synapses a useful vantage point from which to monitor the onset and progression of clinical signs and pathological changes. While murine models of ALS display many features in common with the clinical picture observed in patients, corticospinal tract (CST) involvement is usually less severe in mice than the picture observed in humans. In this paper we describe the characterization of a new conditional transgenic line obtained by targeted integration of a GFP-VAMP2 fusion gene into the Rosa26 locus, and devised to permit the detection of genetically defined presynaptic terminals in wild type mice and murine models of neural disorders. This reporter molecule is selectively enriched in presynaptic boutons, significantly reducing the background signal produced by fibers of passage. The specific features of this reporter line allow us to strongly support the view that murine CST terminals give rise to very few direct contacts with spinal motor neurons. Moreover, the evidence described here reveals the existence of previously uncharacterized, putative direct connections between CST presynaptic boutons and Renshaw neurons in the spinal cord. These results constitute a proof of concept for the potential application of this indicator line to morphological analyses of wild type and diseased synapses.

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Section: Resultssupporting

confidence: 87%

A conditional transgenic reporter of presynaptic terminals reveals novel features of the mouse corticospinal tract

D’Acunzo¹,

Badaloni²,

Ferro³

et al. 2014

Front. Neuroanat.

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“…A comprehensive series of TIFF images from Nop-LacZ animals were uploaded into a database system built on a technological platform described previously (Bjaalie et al 2005; Moene et al 2007). The resource uses a web interface (http://www.rbwb.org, choose tTA-atlas) to access a virtual microscopy tool based on Open Zoom technology (www.openzoom.org) for viewing the scanned images.…”

Section: Methodsmentioning

confidence: 99%

Transgene expression in the Nop-tTA driver line is not inherently restricted to the entorhinal cortex

et al. 2015

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The entorhinal cortex (EC) plays a central role in episodic memory and is among the earliest sites of neurodegeneration and neurofibrillary tangle formation in Alzheimer's disease. Given its importance in memory and dementia, the ability to selectively modulate gene expression or neuronal function in the EC is of widespread interest. To this end, several recent studies have taken advantage of a transgenic line in which the tetracycline transactivator (tTA) was placed under control of the neuropsin (Nop) promoter to limit transgene expression within the medial EC and pre-/parasubiculum. Although the utility of this driver is contingent on its spatial specificity, no detailed neuroanatomical analysis of its expression has yet been conducted. We therefore undertook a systematic analysis of Nop-tTA expression using a lacZ reporter and have made the complete set of histological sections available through the Rodent Brain Workbench tTA atlas, www.rbwb.org. Our findings confirm that the highest density of tTA expression is found in the EC and pre-/parasubiculum, but also reveal considerable expression in several other cortical areas. Promiscuous transgene expression may account for the appearance of pathological protein aggregates outside of the EC in mouse models of Alzheimer's disease using this driver, as we find considerable overlap between sites of delayed amyloid deposition and regions with sparse (β-galactosidase reporter labeling. While different tet-responsive lines can display individual expression characteristics, our results suggest caution when designing experiments that depend on precise localization of gene products controlled by the Nop-tTA or other spatially restrictive transgenic drivers.

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“…These reconciliation processes possess considerable uncertainties, and the data remain very sparse; thus, any comprehensive picture of brain connectivity is not currently possible from such resources. The FACCS (Functional Anatomy of the Cerebro–Cerebellar System) database [29] is a strong effort to map connectivity data into a common spatial framework, but is currently limited in scope to the rat cerebrocerebellar system. Our understanding of the overall architecture of model nervous systems is currently limited to very simple organisms such as the nematode Caenorhabditis elegans [30].…”

Section: Where Are We Now?mentioning

confidence: 99%

A Proposal for a Coordinated Effort for the Determination of Brainwide Neuroanatomical Connectivity in Model Organisms at a Mesoscopic Scale

et al. 2009

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In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is critical, however, for both basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brainwide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brainwide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open-access data repository; compatibility with existing resources; and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.

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Database and tools for analysis of topographic organization and map transformations in major projection systems of the brain

Cited by 25 publications

References 70 publications

A conditional transgenic reporter of presynaptic terminals reveals novel features of the mouse corticospinal tract

A conditional transgenic reporter of presynaptic terminals reveals novel features of the mouse corticospinal tract

Transgene expression in the Nop-tTA driver line is not inherently restricted to the entorhinal cortex

A Proposal for a Coordinated Effort for the Determination of Brainwide Neuroanatomical Connectivity in Model Organisms at a Mesoscopic Scale

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