We investigated whether terminal fibres in the pontine nuclei are arranged in a lamellar pattern ... more We investigated whether terminal fibres in the pontine nuclei are arranged in a lamellar pattern like that demonstrated earlier for pontocerebellar neurones. Following tracer injections in visual and parietal cortices and subsequent computer-based 3-D analysis, we found that labelled corticopontine terminal fibres form numerous sharply delimited aggregates of variable shape. Several of the aggregates are cylindroids (diameter 200-300 microns, length 1-3 mm). The aggregates are confined to a lamellar subspace, the position of which depends on the anteroposterior location of the cortical injections. These findings suggest that the cerebroponto-cerebellar system may be organized according to fairly simple, topographical rules. We discuss the implications of our results in relation to the development of corticopontine topographical organization.
The macroglomerular complex in the primary olfactory center of male moths receives information fr... more 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.
This chapter focuses on the cerebrocerebellar pathway, synaptically interrupted in the pontine nu... more This chapter focuses on the cerebrocerebellar pathway, synaptically interrupted in the pontine nuclei. Recent studies of the primate corticopontine projection show that the neocerebellum—in addition to connections from motor and sensory areas—receives connections from various association areas of the cerebral cortex, some of which are thought to be primarily engaged in cognitive tasks. The anatomic data on the origin of corticopontine fibers needs to be supplemented with physiological experiments to clarify their functional properties at the single-cell level. The scarcity of corticopontine connections from the prefrontal cortex in the monkey may not seem readily compatible with a prominent role of the neocerebellum in certain cognitive tasks. Corticopontine and pontocerebellar lamellae have similar shapes and orientations but appear to differ in other respects. Corticopontine terminal fields are sharply delimited, apparently without gradual overlap between projections from different sites in the cortex, whereas pontocerebellar lamellae are fuzzier and exhibit gradual overlap of neuronal populations projecting to different targets.
Proceedings of The National Academy of Sciences, 2001
Neuronal synchronization in the olfactory bulb has been proposed to arise from a diffuse action o... more Neuronal synchronization in the olfactory bulb has been proposed to arise from a diffuse action of glutamate released from mitral cells (MC, olfactory bulb relay neurons). According to this hypothesis, glutamate spills over from dendrodendritic synapses formed between MC and granule cells (GC, olfactory bulb interneurons) to activate neighboring MC. The excitation of MC is balanced by a strong inhibition
Assignment of anatomical reference is a key step in integration of the rapidly expanding collecti... more Assignment of anatomical reference is a key step in integration of the rapidly expanding collection of rodent brain data. Landmark-based registration facilitates spatial anchoring of diverse types of data not suitable for automated methods operating on voxel-based image information. Here we propose a standardized set of anatomical landmarks for registration of whole brain imaging datasets from the mouse and rat brain, and in particular for integration of experimental image data in Waxholm Space (WHS). Sixteen internal landmarks of the C57BL/6J mouse brain have been reliably identified: by different individuals, independent of their experience in anatomy; across different MRI contrasts (T1, T2, T2(*)) and other modalities (Nissl histology and block-face anatomy); in different specimens; in different slice acquisition angles; and in different image resolutions. We present a registration example between T1-weighted MRI and the mouse WHS template using these landmarks and reaching fairl...
The pontine nuclei provide the cerebellar hemispheres with the majority of their mossy fiber affe... more The pontine nuclei provide the cerebellar hemispheres with the majority of their mossy fiber afferents, and receive their main input from the cerebral cortex. Even though the vast majority of pontine neurons send their axons to the cerebellar cortex, and are contacted monosynaptically by (glutamatergic) corticopontine fibers, the information-processing taking place is not well understood. In addition to typical projection neurons, the pontine nuclei contain putative GABA-ergic interneurons and complex synaptic arrangements. The corticopontine projection is characterized by a precise but highly divergent terminal pattern. Large and functionally diverse parts of the cerebral cortex contribute; in the monkey the most notable exception is the almost total lack of projections from large parts of the prefrontal and temporal cortices. Within corticopontine projections from visual and somatosensory areas there is a de-emphasis of central vision and distal parts of the extremities as compared with other connections of these sensory areas. Subcorticopontine projections provide only a few percent of the total input to the pontine nuclei. Certain cell groups, such as the reticular formation, project in a diffuse manner whereas other nuclei, such as the mammillary nucleus, project to restricted pontine regions only, partially converging with functionally related corticopontine connections. The pontocerebellar projection is characterized by a highly convergent pattern, even though there is also marked divergence. Neurons projecting to a single cerebellar folium appear to be confined to a lamella-shaped volume in the pontine nuclei. The organization of the pontine nuclei suggests that they ensure that information from various, functionally diverse, parts of the cerebral cortex and subcortical nuclei are brought together and integrated in the cerebellar cortex.
The major cortical-subcortical re-entrant pathways through the basal ganglia and cerebellum are c... more 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.
This study deals with three different aspects of the organization of connections from the cingula... more This study deals with three different aspects of the organization of connections from the cingulate gyrus to the cerebellum. (1) With the use of wheat germ agglutinin-horseradish peroxidase as a retrograde tracer, the distribution of cingulate neurons projecting to the pontine nuclei was studied. Retrogradely labeled cells were found in layer 5 in all parts of the cingulate gyrus. Average densities of cingulo-pontine cells were similar in the different cytoarchitectonic subdivisions, although some density gradients were observed. The projection was found to be remarkably strong. Average densities of corticopontine cells in the cingulate gyrus ranged from 500-700 cells per mm2 cortical surface, and the total number of neurons was in the range of 75,000-105,000 (n = 4). (2) A topographical organization of terminal fields of fibers originating in different parts of the cingulate gyrus was demonstrated with the combined use of anterograde degeneration and anterograde transport of wheat germ agglutinin-horseradish peroxidase. Terminal fibers originating in different zones of the cingulate gyrus were distributed in a patchy mosaic within a narrow band along the ventromedial aspect of the pontine nuclei. (3) We confirm, with the combined use of lesions in the cingulate gyrus and injections of wheat germ agglutinin-horseradish peroxidase in the ventral paraflocculus, that there is considerable overlap between terminal fibers originating in the cingulate gyrus, and cells retrogradely labeled from the ventral paraflocculus. The role of the ventral paraflocculus as a receiver of "limbic" input is discussed.
This article presents a computer program, Micro3D, designed for 3-D reconstruction, visualization... more 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/).
To understand the relationship between structure and function in specific brain regions, it is ne... more 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.
We investigated whether terminal fibres in the pontine nuclei are arranged in a lamellar pattern ... more We investigated whether terminal fibres in the pontine nuclei are arranged in a lamellar pattern like that demonstrated earlier for pontocerebellar neurones. Following tracer injections in visual and parietal cortices and subsequent computer-based 3-D analysis, we found that labelled corticopontine terminal fibres form numerous sharply delimited aggregates of variable shape. Several of the aggregates are cylindroids (diameter 200-300 microns, length 1-3 mm). The aggregates are confined to a lamellar subspace, the position of which depends on the anteroposterior location of the cortical injections. These findings suggest that the cerebroponto-cerebellar system may be organized according to fairly simple, topographical rules. We discuss the implications of our results in relation to the development of corticopontine topographical organization.
The macroglomerular complex in the primary olfactory center of male moths receives information fr... more 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.
This chapter focuses on the cerebrocerebellar pathway, synaptically interrupted in the pontine nu... more This chapter focuses on the cerebrocerebellar pathway, synaptically interrupted in the pontine nuclei. Recent studies of the primate corticopontine projection show that the neocerebellum—in addition to connections from motor and sensory areas—receives connections from various association areas of the cerebral cortex, some of which are thought to be primarily engaged in cognitive tasks. The anatomic data on the origin of corticopontine fibers needs to be supplemented with physiological experiments to clarify their functional properties at the single-cell level. The scarcity of corticopontine connections from the prefrontal cortex in the monkey may not seem readily compatible with a prominent role of the neocerebellum in certain cognitive tasks. Corticopontine and pontocerebellar lamellae have similar shapes and orientations but appear to differ in other respects. Corticopontine terminal fields are sharply delimited, apparently without gradual overlap between projections from different sites in the cortex, whereas pontocerebellar lamellae are fuzzier and exhibit gradual overlap of neuronal populations projecting to different targets.
Proceedings of The National Academy of Sciences, 2001
Neuronal synchronization in the olfactory bulb has been proposed to arise from a diffuse action o... more Neuronal synchronization in the olfactory bulb has been proposed to arise from a diffuse action of glutamate released from mitral cells (MC, olfactory bulb relay neurons). According to this hypothesis, glutamate spills over from dendrodendritic synapses formed between MC and granule cells (GC, olfactory bulb interneurons) to activate neighboring MC. The excitation of MC is balanced by a strong inhibition
Assignment of anatomical reference is a key step in integration of the rapidly expanding collecti... more Assignment of anatomical reference is a key step in integration of the rapidly expanding collection of rodent brain data. Landmark-based registration facilitates spatial anchoring of diverse types of data not suitable for automated methods operating on voxel-based image information. Here we propose a standardized set of anatomical landmarks for registration of whole brain imaging datasets from the mouse and rat brain, and in particular for integration of experimental image data in Waxholm Space (WHS). Sixteen internal landmarks of the C57BL/6J mouse brain have been reliably identified: by different individuals, independent of their experience in anatomy; across different MRI contrasts (T1, T2, T2(*)) and other modalities (Nissl histology and block-face anatomy); in different specimens; in different slice acquisition angles; and in different image resolutions. We present a registration example between T1-weighted MRI and the mouse WHS template using these landmarks and reaching fairl...
The pontine nuclei provide the cerebellar hemispheres with the majority of their mossy fiber affe... more The pontine nuclei provide the cerebellar hemispheres with the majority of their mossy fiber afferents, and receive their main input from the cerebral cortex. Even though the vast majority of pontine neurons send their axons to the cerebellar cortex, and are contacted monosynaptically by (glutamatergic) corticopontine fibers, the information-processing taking place is not well understood. In addition to typical projection neurons, the pontine nuclei contain putative GABA-ergic interneurons and complex synaptic arrangements. The corticopontine projection is characterized by a precise but highly divergent terminal pattern. Large and functionally diverse parts of the cerebral cortex contribute; in the monkey the most notable exception is the almost total lack of projections from large parts of the prefrontal and temporal cortices. Within corticopontine projections from visual and somatosensory areas there is a de-emphasis of central vision and distal parts of the extremities as compared with other connections of these sensory areas. Subcorticopontine projections provide only a few percent of the total input to the pontine nuclei. Certain cell groups, such as the reticular formation, project in a diffuse manner whereas other nuclei, such as the mammillary nucleus, project to restricted pontine regions only, partially converging with functionally related corticopontine connections. The pontocerebellar projection is characterized by a highly convergent pattern, even though there is also marked divergence. Neurons projecting to a single cerebellar folium appear to be confined to a lamella-shaped volume in the pontine nuclei. The organization of the pontine nuclei suggests that they ensure that information from various, functionally diverse, parts of the cerebral cortex and subcortical nuclei are brought together and integrated in the cerebellar cortex.
The major cortical-subcortical re-entrant pathways through the basal ganglia and cerebellum are c... more 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.
This study deals with three different aspects of the organization of connections from the cingula... more This study deals with three different aspects of the organization of connections from the cingulate gyrus to the cerebellum. (1) With the use of wheat germ agglutinin-horseradish peroxidase as a retrograde tracer, the distribution of cingulate neurons projecting to the pontine nuclei was studied. Retrogradely labeled cells were found in layer 5 in all parts of the cingulate gyrus. Average densities of cingulo-pontine cells were similar in the different cytoarchitectonic subdivisions, although some density gradients were observed. The projection was found to be remarkably strong. Average densities of corticopontine cells in the cingulate gyrus ranged from 500-700 cells per mm2 cortical surface, and the total number of neurons was in the range of 75,000-105,000 (n = 4). (2) A topographical organization of terminal fields of fibers originating in different parts of the cingulate gyrus was demonstrated with the combined use of anterograde degeneration and anterograde transport of wheat germ agglutinin-horseradish peroxidase. Terminal fibers originating in different zones of the cingulate gyrus were distributed in a patchy mosaic within a narrow band along the ventromedial aspect of the pontine nuclei. (3) We confirm, with the combined use of lesions in the cingulate gyrus and injections of wheat germ agglutinin-horseradish peroxidase in the ventral paraflocculus, that there is considerable overlap between terminal fibers originating in the cingulate gyrus, and cells retrogradely labeled from the ventral paraflocculus. The role of the ventral paraflocculus as a receiver of "limbic" input is discussed.
This article presents a computer program, Micro3D, designed for 3-D reconstruction, visualization... more 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/).
To understand the relationship between structure and function in specific brain regions, it is ne... more 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.
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