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Jan G Bjaalie

Publications and source records attributed to Jan G Bjaalie.

14 recordsLinked to original sources

Expression mapping of tetracycline-responsive prion protein promoter: digital atlasing for generating cell-specific disease models.

We present a digital atlas system that allows mapping of molecular expression patterns at cellular resolution through large series of histological sections. Using this system, we have mapped the distribution of a distinct marker, encoded by the LacZ reporter gene driven by the tetracycline-responsive prion protein promoter in double transgenic mice. The purpose is to evaluate the suitability of this promoter mouse line for targeting genes of interest to specific brain regions, essential for construction of inducible transgenic disease models. Following processing to visualize the promoter expression, sections were counterstained to simultaneously display cytoarchitectonics. High-resolution mosaic images covering entire coronal sections were collected through the mouse brain at intervals of 200 microm. A web-based application provides access to a customized virtual microscopy tool for viewing and navigation within and across the section images. For each section image, the nearest section in a standard atlas is defined, and annotations of key structures and regions inserted. Putative categorization of labeled cells was performed with use of distribution patterns, followed by cell size and shape, as parameters that were compared to legacy data. Among the ensuing results were expression of this promoter in putative glial cells in the cerebellum (and not in Purkinje cells), in putative glial cells in the substantia nigra, in pallidal glial cells or interneurons, and in distinct cell layers and regions of the hippocampus. The study serves as a precursor for a database resource allowing evaluation of the suitability of different promoter mouse lines for generating disease models.

Animals↗

Micro3D: computer program for three-dimensional reconstruction visualization, and analysis of neuronal populations and barin regions.

This article presents a computer program, Micro3D, designed for 3-D reconstruction, visualization, and analysis of coordinate-data (points and lines) recorded from serial sections. The software has primarily been used for studying shapes and dimension of brain regions (contour line data) and distributions of cellular elements such as neuronal cell bodies or axonal terminal fields labeled with tract-tracing techniques (point data). The tissue elements recorded could equally well be labeled with use of other techniques, the only requirement being that the data collected are saved as x,y,z coordinates. Data are typically imported from image-combining computerized microscopy systems or image analysis systems, such as Neurolucida (MicroBrightField, Colchester, VT) or analySIS (Soft Imaging System, Gmbh, Münster, Germany). System requirements are a PC running LINUX. Reconstructions in Micro3D may be rotated and zoomed in real-time, and submitted to perspective viewing and stereo-imaging. Surfaces are re-synthesized on the basis of stacks of contour lines. Clipping is used for defining section-independent subdivisions of the reconstruction. Flattening of curved sheets of points layers (e.g., neurons in a layer) facilitates inspection of complicated distribution patterns. Micro3D computes color-coded density maps. Opportunities for translation of data from different reconstructions into common coordinate systems are also provided. This article demonstrates the use of Micro3D for visualization of complex neuronal distribution patterns in somatosensory and auditory systems. The software is available for download on conditions posted at the NeSys home pages (http://www.nesys.uio.no/) and at The Rodent Brain Workbench (http://www.rbwb.org/).

Animals↗

Topographical organization of pathways from somatosensory cortex through the pontine nuclei to tactile regions of the rat cerebellar hemispheres.

The granule cell layer of the cerebellar hemispheres contains a patchy and noncontinuous map of the body surface, consisting of a complex mosaic of multiple perioral tactile representations. Previous physiological studies have shown that cerebrocerebellar mossy fibre projections, conveyed through the pontine nuclei, are mapped in registration with peripheral tactile projections to the cerebellum. In contrast to the fractured cerebellar map, the primary somatosensory cortex (SI) is somatotopically organized. To understand better the map transformation occurring in cerebrocerebellar pathways, we injected axonal tracers in electrophysiologically defined locations in Sprague-Dawley rat folium crus IIa, and mapped the distribution of retrogradely labelled neurons within the pontine nuclei using three-dimensional (3-D) reconstructions. Tracer injections within the large central upper lip patch in crus IIa-labelled neurons located centrally in the pontine nuclei, primarily contralateral to the injected side. Larger injections (covering multiple crus IIa perioral representations) resulted in labelling extending only slightly beyond this region, with a higher density and more ipsilaterally labelled neurons. Combined axonal tracer injections in upper lip representations in SI and crus IIa, revealed a close spatial correspondence between the cerebropontine terminal fields and the crus IIa projecting neurons. Finally, comparisons with previously published three-dimensional distributions of pontine neurons labelled following tracer injections in face receiving regions in the paramedian lobule (downloaded from http://www.rbwb.org) revealed similar correspondence. The present data support the coherent topographical organization of cerebro-ponto-cerebellar networks previously suggested from physiological studies. We discuss the present findings in the context of transformations from cerebral somatotopic to cerebellar fractured tactile representations.

Animals↗

Pontine maps linking somatosensory and cerebellar cortices are in register with climbing fiber somatotopy.

The cerebropontocerebellar mossy fiber system is a major CNS sensorimotor pathway. We used a double-retrograde axonal tracing technique (red and green beads) to chart in rats the pontocerebellar projection to different electrophysiologically defined climbing fiber zones in the posterior lobe (face-receiving A2 zone and forelimb- and hindlimb-receiving parts of the C1 zone in the paramedian lobule and copula pyramidis, respectively). Individual cortical injection sites were verified as located in a given zone by mapping the pattern of cell labeling in the inferior olive, whereas labeled cells in the pontine nuclei were mapped using computer-aided three-dimensional reconstruction techniques. A number of topographical differences were found for the pontine projection to the individual zones. Projections to the A2 zone were bilateral, whereas to both parts of the C1 zone, the inputs were mainly contralateral. Furthermore, the A2 (face), C1 (forelimb), and C1 (hindlimb) zone projections were centered in progressively more caudal parts of the pontine nuclei with little or no overlap between them. The areas occupied by cell labeling for each zone corresponded closely to territories in the pontine nuclei shown previously to receive projections from somatotopically equivalent regions of the somatosensory cortex. This precise cerebropontocerebellar topography, defined by climbing fiber somatotopy, is a new principle of organization for linking somatosensory and cerebellar cortices. The convergence of direct and indirect sensory projections is likely to have important implications for cerebellar cortical processing.

Afferent Pathways↗

Projections of male-specific receptor neurons in the antennal lobe of the Oriental tobacco budworm moth, Helicoverpa assulta: a unique glomerular organization among related species.

The macroglomerular complex in the primary olfactory center of male moths receives information from numerous pheromone-detecting receptor neurons housed in specific sensilla located on the antennae. We investigated the functional organization of the three glomeruli constituting this complex in Helicoverpa assulta, a unique species among heliothine moths as concerns the composition of the pheromone blend. By tip recordings from the male-specific receptor neurons combined with cobalt-lysine stainings, the axon terminals in the brain were traced and subsequently reconstructed by camera lucida drawings. Some were also reconstructed in a digital form. The results showed that the sensilla could be classified into two functional types. A major category housed two colocalized receptor neurons, one responding to the primary pheromone component cis-9-hexadecenal and the other to the behavioral antagonists cis-9-tetradecenal and cis-9-hexadecenol. Cobalt-lysine applied to this sensillum type consistently resulted in two stained axons, each terminating in one of the two large subunits of the macroglomerular complex: the cumulus or the dorsomedial glomerulus. The second, less frequently appearing sensillum type contained a receptor neuron responding to the second pheromone component, cis-11-hexadecenal. Dye applied to this type resulted in stained axon projections in the ventral glomerulus. In an evolutionary context it is particularly interesting that differences of related heliothine species are reflected in the functional organization of the MGC compartments.

Action Potentials↗

Three-dimensional topography of corticopontine projections from rat sensorimotor cortex: comparisons with corticostriatal projections reveal diverse integrative organization.

The major cortical-subcortical re-entrant pathways through the basal ganglia and cerebellum are considered to represent anatomically segregated channels for information originating in different cortical areas. A capacity for integrating unique combinations of cortical inputs has been well documented in the basal ganglia circuits but is largely undefined in the precerebellar circuits. To compare and quantify the amount of overlap that occurs in the first link of the cortico-ponto-cerebellar pathway, a dual tracing approach was used to map the spatial relationship between projections originating from the primary somatosensory cortex (SI), the secondary somatosensory cortex (SII), and the primary motor cortex (MI). The anterograde tracers biotinylated dextran amine and Fluoro-Ruby were injected into homologous whisker representations of either SI and SII, or SI and MI. The ensuing pontine labeling patterns were analyzed using a computerized three-dimensional reconstruction approach. The results demonstrate that whisker-related projections from SI and MI are largely segregated. At some locations, the two projections are adjoining and partly overlapping. Furthermore, SI contributes significantly more corticopontine projections than MI. By comparison, projections from corresponding representations in SI and SII terminate in similar parts of the pontine nuclei and display considerable amounts of spatial overlap. Finally, comparison of corticopontine and corticostriatal projections in the same experimental animals reveals that SI-SII overlap is significantly larger in the pontine nuclei than in the neostriatum. These structural differences indicate a larger capacity for integration of information within the same sensory modality in the pontocerebellar system compared to the basal ganglia.

Animals↗

The relationship between hodological and cytoarchitectonic organization in the vestibular complex of the 11-day chicken embryo.

To understand the relationship between structure and function in specific brain regions, it is necessary to ascertain which anatomical features are physiologically relevant. Physiological studies of brain function traditionally have been set in the context of anatomical features based on cytoarchitectonics and myeloarchitectonics, but the relationship between structure and function in this context can be complex. Alternative schemes of anatomical organization, such as that based on hodology (the mapping of projections) may provide greater insight. Here, we make a direct comparison of the hodological and the cytoarchitectonic organization of the vestibular complex in the mid-term chicken embryo, using retrograde tracing and three-dimensional reconstruction. In one set of experiments, vestibulospinal and vestibulo-ocular neuron groups were selectively labeled with biotin dextran-amines and aligned with the cytoarchitectonically defined vestibular nuclei in alternating sections that were then combined into intercalated three-dimensional models. This allowed a semiquantitative analysis of the apportionment of individual hodological groups among cytoarchitectonic nuclei. In another set of experiments, vestibulospinal and vestibulo-ocular neuron groups were labeled differentially with fluorescent dextran-amines, three-dimensionally reconstructed, and subjected to a quantitative analysis of spatial overlap. Our results provide the first three-dimensional representation and quantitative analysis of the hodological compartmentalization of the vestibular complex (the "hodological mosaic"). They also show directly how each hodologically defined neuron group relates to the conventional vestibular nuclei, underscoring the fact that the units of the hodological mosaic do not bear a one-to-one correspondence to the cytoarchitectonic nuclear divisions. Some hodologically defined groups are localized to restricted portions of a nucleus, whereas others overlap multiple nuclei. Thus, hodology and cytoarchitectonic features appear to be separately regulated in the vestibular complex of the chicken embryo, possibly through different sets of positional specification mechanisms. The three-dimensional representations we present here provide a foundation for integrating anatomical, physiological, developmental, and evolutionary studies of the vestibular system.

Animals↗

Neuroscience data and tool sharing: a legal and policy framework for neuroinformatics.

The requirements for neuroinformatics to make a significant impact on neuroscience are not simply technical--the hardware, software, and protocols for collaborative research--they also include the legal and policy frameworks within which projects operate. This is not least because the creation of large collaborative scientific databases amplifies the complicated interactions between proprietary, for-profit R&D and public "open science." In this paper, we draw on experiences from the field of genomics to examine some of the likely consequences of these interactions in neuroscience. Facilitating the widespread sharing of data and tools for neuroscientific research will accelerate the development of neuroinformatics. We propose approaches to overcome the cultural and legal barriers that have slowed these developments to date. We also draw on legal strategies employed by the Free Software community, in suggesting frameworks neuroinformatics might adopt to reinforce the role of public-science databases, and propose a mechanism for identifying and allowing "open science" uses for data whilst still permitting flexible licensing for secondary commercial research.

Computational Biology↗

In vivo tracing of major rat brain pathways using manganese-enhanced magnetic resonance imaging and three-dimensional digital atlasing.

The magnetic resonance imaging (MRI)-detectable T1 contrast agent manganese (Mn2+) has recently been introduced as a neural tracer in rodents, birds, and monkeys. We have tested to what extent this in vivo method is useful for three-dimensional (3-D) survey of connectivity patterns in the rat somatosensory system. A commonly available 3 T human clinical MRI scanner was used to trace neural pathways following focal injection of manganese chloride (MnCl2) in the somatosensory cortex. Six to 10 h after MnCl2 injection, we found significant signal enhancement in major projection systems, including corticocortical, corticostriatal, corticothalamic, corticotectal, corticopontine, and corticospinal pathways. To facilitate the assignment of anatomic localization to the observed Mn2+ signal enhancement, we registered the MRI data with a 3-D digital reconstruction of a stereotaxic rat brain atlas. Across-animal comparison using the digital model allowed demonstration of a corticothalamic 3-D topographic organization in agreement with previously published two-dimensional topographic schemes based on classical neural tracing data. We conclude that anterograde MnCl2/MRI tracing allows rapid analysis of topographic organization across multiple brain regions. The method allows a higher data throughput for 3-D studies of large-scale brain connectivity than conventional methods based on tissue sectioning.

Animals↗

GABA and GABAA receptors at hippocampal mossy fibre synapses.

Anatomical and electrophysiological evidence has raised the possibility that corelease of GABA and glutamate occurs at hippocampal mossy fibre synapses which, however, lack the vesicular GABA transporter VGAT. Here, we apply immunogold cytochemistry to show that GABA, like glutamate, has a close spatial relation to synaptic vesicles in rat mossy fibre terminals, implying that a mechanism exists to package GABA in synaptic vesicles. We also show that GABAA and AMPA receptors are colocalized at mossy fibre synapses. The expression of GABA and GABAA receptors is, however, weaker than in inhibitory synapses. Electrical stimuli that recruit mossy fibres evoke monosynaptic GABAA receptor-mediated signals in post-synaptic targets that show marked frequency-dependent facilitation and sensitivity to group II metabotropic receptors, two features that are characteristic of mossy fibre transmission. These results provide further evidence for GABA and glutamate cotransmission at mossy fibre synapses, although paired pre- and post-synaptic recordings will be required to determine the role of GABA at this unusual synapse.

Animals↗

Neuroinformatics: the integration of shared databases and tools towards integrative neuroscience.

There is significant interest amongst neuroscientists in sharing neuroscience data and analytical tools. The exchange of neuroscience data and tools between groups affords the opportunity to differently re-analyze previously collected data, encourage new neuroscience interpretations and foster otherwise uninitiated collaborations, and provide a framework for the further development of theoretically based models of brain function. Data sharing will ultimately reduce experimental and analytical error. Many small Internet accessible database initiatives have been developed and specialized analytical software and modeling tools are distributed within different fields of neuroscience. However, in addition large-scale international collaborations are required which involve new mechanisms of coordination and funding. Provided sufficient government support is given to such international initiatives, sharing of neuroscience data and tools can play a pivotal role in human brain research and lead to innovations in neuroscience, informatics and treatment of brain disorders. These innovations will enable application of theoretical modeling techniques to enhance our understanding of the integrative aspects of neuroscience. This article, authored by a multinational working group on neuroinformatics established by the Organization for Economic Co-operation and Development (OECD), articulates some of the challenges and lessons learned to date in efforts to achieve international collaborative neuroscience.

Computational Biology↗

Comparison of semi-automatic and automatic data acquisition methods for studying three-dimensional distributions of large neuronal populations and axonal plexuses.

Neuroanatomy is in need of high throughput methods for reliably recording the distribution of tissue elements across large brain regions. We compared two methods for recording the spatial distribution of identified neuronal elements such as tracer labelled cell bodies or axonal plexuses. The methods compared were computerized image-combining microscopy (semi-automatic method), which is a user controlled method providing feedback during digitization, and digital camera technology with image analysis software (automatic method). Both methods were applied to biotinylated dextran amine labelled axonal plexuses and FluoroRuby labelled neuronal cell bodies, in the pontine nuclei of the rat. Coordinates were assigned to the labelled elements using both methods. The ensuing distribution patterns were compared, section by section, and in three-dimensional reconstruction. The experienced investigator, using the semi-automatic method, could detect individual axons, fragments of axons, weakly labelled elements, and overlapping cell bodies, better than the automatic system. Nevertheless, both methods detected the overall distribution of the labelled axons and cells investigated. Automatic methods provide opportunities for efficient large-scale data acquisition of labelled neuronal elements.

Animals↗