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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↗

On the absence of a rubrothalamic projection in the monkey with observations on some ascending mesencephalic projections.

In order to determine whether there is a rubrothalamic projection in the rhesus monkey, the ascending degeneration resulting from electrolytic lesions made in the red nucleus and adjacent mesencephalon in animals surviving at least one year after bilateral interruption of the superior cerebellar peduncles (PCS) was studied by means of the Fink-Heimer technique. In a necessary preliminary step it was shown that virtually all of the degeneration disappeared from the thalamus within twelve months after PCS interruption so that degeneration resulting from the subsequent electrolytic mesencephalic lesions could be attributed to interruption of non-cerebellar ascending fibres. The results show that degeneration was present in the thalamus following the electrolyte mesencephalic-diencephalic lesions but it could be accounted for on the basis of damage either to residual PCS fibres, to somatosensory pathways, to intrathalamic connections or to cell groups or projection fibres of the reticular formation, substantia nigra or globus pallidus. It is concluded that there is no direct rubrothalamic projection in the monkey and, in particular, no evidence of a projection from the red nucleus to the ventral lateral or ventral anterior thalamic nuclei. The results also indicate that the mesencephalic reticular formation is the main source of ascending afferents to the nucelus reticularis thalami. Some observations were made concerning nigrostriatal and nigrothalamic projections. Retrograde cell changes resulting from unilateral lesions made caudal to the red nucleus were studied in three animals. The observed cell changes are interpreted as being consistent with the conclusion that there is no rubrothalamic projection.

Age Factors↗

Visual projections induced into the auditory pathway of ferrets. I. Novel inputs to primary auditory cortex (AI) from the LP/pulvinar complex and the topography of the MGN-AI projection.

The organization of cortical circuitry responsible for processing sensory information is a subject of intense examination. However, it is not known whether cortical cells in different sensory cortices process information in a way that is specific to the modality of their input, or whether there are commonalities in processing circuitry across different cortices. In our laboratory, this question has been investigated at the level of the geniculocortical pathway by routing information of one sensory modality into the processing circuitry of another modality. Appropriate early lesions cause growth of retinal axons into the auditory thalamus (MGN) (Sur et al., Science 242:1437, '88). Previously, we have established that the MGN carries the resulting visual information on to primary auditory cortex (AI), which thus contains visually responsive neurons and a topographic representation of the retina (Roe et al., Soc. Neurosci. Abstr. 14:460, '88; Sur et al., Science 242:1437, '88). In this paper, we describe anomalous projections from the dorsal part of the thalamus, specifically the lateral posterior/pulvinar complex, into AI. This result demonstrates that thalamic neurons belonging to one modality can be induced to project to cortex that is normally of a different modality. In addition, we have studied in detail the nature of the MGN to AI projection in these animals as compared to the normal projection. The MGN to AI projection appears to be unaltered by the lesions; the location and topography of labelled cells are similar to that in normal animals. Because the MGN to AI projection is still highly divergent along the "isofrequency" dimension when compared to the tonotopic dimension, our data suggest that visual topography in the cortical map is created within the auditory cortex, perhaps by activity-dependent sharpening of the retinal representation during development.

Animals↗

Quantitative study of the tectally projecting retinal ganglion cells in the adult frog: I. The size of the contralateral and ipsilateral projections.

The proportion of ganglion cells connected to the several central targets of the retinal projection varies in different species. In the frog, the retinotectal projection is clearly the largest branch of the optic pathway and the relative size of the tectally projecting population can be expected to be correspondingly great. However, there have been no studies aimed at quantifying the size of this population and at partitioning its contralateral and ipsilateral components. We injected the tectum with horseradish peroxidase (HRP) dried onto fine needles to count the numbers of retinal ganglion cells labeled by retrograde transport. The retinas were prepared as flat-mounts to facilitate the cell counting. The tecta were injected either unilaterally or bilaterally in mirror-symmetric loci. Specimens included completely normal frogs and frogs which had undergone unilateral optic nerve regeneration, although only normal retinas are presented in the current study. The retrograde transport interval was varied progressively (from 3 to 5 days), and single or multiple injections of HRP were placed singly or as clusters, in order to increment the cell counts toward a level of saturation. Approximately 70.9% of the neurons in the ganglion cell layer could be labeled by this method. Correcting for the presence of displaced amacrine cells, estimated to comprise approximately 16% of the neurons in the ganglion cell layer (Scalia et al., '85, Brain Res. 344:267-280), we calculate that approximately 84.4% of the retinal ganglion cells project contralaterally to the optic tectum. Flat-mounted retinas ipsilateral to unilaterally injected tecta of completely normal frogs were also examined for labeled cells. The results of injections in the rostrolateral, caudomedial, and caudolateral tectum were studied. We found that ipsilaterally labeled cells comprised no more than 2.3% of the overall population of ganglion cells in the ganglion cell layer. The ipsilaterally projecting cells were found in loci which were approximately mirror-symmetric to the regions of maximal cell labeling in the contralateral retinas from the same animals. The ipsilateral population was always displaced toward the periphery of the retina with respect to the contralateral population, regardless of whether the contralateral locus was centered in the temporal, ventronasal, or dorsonasal sector of the retina. Because the ipsilaterally projecting ganglion cells form such a minor population, and because they exist in the monocular as well as the binocular parts of the retina, it seems likely that they may not play a significant role in visual function in the frog.

Afferent Pathways↗

Organization of ascending hypothalamic projections to the rostral forebrain with special reference to the innervation of cholinergic projection neurons.

Axonal projections from hypothalamic nuclei to the basal forebrain, and their relation to cholinergic projection neurons in particular, were studied in the rat by using the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in combination with choline acetyltransferase (ChAT) immunocytochemistry. Discrete iontophoretic PHA-L injections were delivered to different portions of the caudal lateral hypothalamus, as well as to various medial hypothalamic areas, including the ventromedial, dorsomedial, and paraventricular nuclei, and anterior hypothalamic and medial preoptic areas. The simultaneous detection of PHA-L-labeled fibers/terminals and ChAT-positive neurons was performed by using nickel-enhanced diaminobenzidine (DAB) and nonenhanced DAB as chromogens. Selected cases were investigated at the electron microscopic level. Ascending hypothalamic projections maintained an orderly lateromedial arrangement within the different components of the medial forebrain bundle, as well as with respect to their terminal projection fields (e.g., within the bed nucleus of the stria terminalis and lateral septal nucleus). The distribution pattern of hypothalamic inputs to cholinergic projection neurons corresponded to the topography of ascending hypothalamic axons. Axons originating from neurons in the far-lateral hypothalamus reached cholinergic neurons in a zone that extended from the dorsal part of the sublenticular substantia innominata (SI) caudolaterally, to the lateral portion of the bed nucleus of the stria terminalis rostromedially, encompassing a narrow band along the ventral part of the globus pallidus and medial portion of the internal capsule. Axons originating from cells in the medial portion of the lateral hypothalamus reached cholinergic cells primarily in more medial and ventral parts of the SI, and in the magnocellular preoptic nucleus and horizontal limb of the diagonal band nucleus (HDB). Axons from medial hypothalamic cells appeared to contact cholinergic neurons primarily in the medial part of the HDB, and in the medial septum/vertical limb of the diagonal band complex. Electron microscopic double-labeling experiments confirmed contacts between labeled terminals and cholinergic cells in the HDB and SI. Individual hypothalamic axons established synapses with both cholinergic and noncholinergic neuronal elements in the same regions. These findings have important implications for our understanding of the organization of afferents to the basal forebrain cholinergic projection system.

Afferent Pathways↗

Glutamatergic hippocampal formation projections to prefrontal cortex in the rat are regulated by GABAergic inhibition and show convergence with glutamatergic projections from the limbic thalamus.

Anatomic and physiologic studies in the rat have shown projections from the hippocampal formation (HF) and mediodorsal (MD) thalamic nucleus to the medial prefrontal cortex (mPFC). The authors used multi-barrel iontophoresis to: confirm the neurotransmitter used in the projection from HF to mPFC; investigate the role of GABAergic inhibition in the regulation of this projection; and examine the functional convergence of projections from HF and MD onto single mPFC neurons. During HF stimulation, nine cells (6%) showed excitation followed by prolonged inhibition, 39 cells (26%) showed prolonged inhibition alone and 100 cells (68%) showed no clear response. In a further 12 cells that showed no predrug excitation to HF stimulation (representing 16% of the cells in this category), iontophoresis of the GABAA antagonist bicuculline methiodide (BMI) revealed excitatory responses. A total of six mPFC cells (38% of the cells showing excitatory responses to HF stimulation) showed convergent excitation to HF and MD thalamic (or adjacent paratenial nucleus) stimulation. Five out of eight (63%) of the predrug or BMI-revealed excitatory responses of mPFC neurons to HF stimulation were selectively decreased after AMPA antagonist iontophoresis (either CNQX or DNQX). These data confirm that the HF projection to prefrontal cortex is, at least in part, glutamatergic; suggest that the responses of mPFC neurons to activity in this HF pathway are regulated by GABAergic inhibition; and indicate that projections from HF and MD converge onto single mPFC neurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Topographic projections from the basal ganglia to the nucleus tegmenti pedunculopontinus pars compacta of the cat with special reference to pallidal projection.

Projections from the basal ganglia to the nucleus tegmenti pedunculopontinus pars compacta (TPC) were studied by using anterograde and retrograde tracing techniques with horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) in the cat. Following WGA-HRP injections into the medial TPC area, a substantial number of retrogradely labeled cells were seen in the entopeduncular nucleus (EP) and medial half of the substantia nigra pars reticulata (SNr), whereas following WGA-HRP injections into the lateral TPC area, labeled cells were marked in the caudal half of the globus pallidus (GP) and lateral half of the SNr. To confirm the retrograde tracing study, WGA-HRP was injected into the EP or the caudal GP, and anterograde labeling was observed in the TPC areas. Terminal labeling was located in the medial TPC area in the EP injection case, while terminal labeling was observed in the lateral TPC area in the caudal GP injection case. Projections from the striatum to the pallidal complex (the EP and the caudal GP) were also studied autoradiographically by injecting amino acids into various parts of the caudate nucleus and the putamen. Terminal labeling was distributed over the whole extent of the EP and the rostral GP following injections into the rostral striatum (the head of the caudate nucleus or the rostral part of the putamen), while terminal labeling was distributed over the caudal GP following injections into the caudal striatum (the body of the caudate nucleus or the caudal part of the putamen). From these findings, we conclude that there exists a medio-lateral topography in the projection from the basal ganglia to the TPC: The EP receives afferent projections from the rostral striatum and projects to the medial TPC area, whereas the caudal GP receives projections from the caudal striatum and sends fibers to the lateral TPC area.

Animals↗

Easy detection of tumor in oncologic whole-body PET by projection reconstruction images with maximum intensity projection algorithm.

Whole-body PET scanning for an oncology study produces a large number of transaxial images by data acquisition over multiple bed positions. The sagittal and coronal reformatted images are often used for better understanding of radioisotope distribution. We reduced the number of PET images by calculating projection images and evaluated the merit of additional data processing for the visualization and detection of tumors. After reconstructing whole-body 18F-FDG PET images (6-8 bed positions) of eight cancer patients, antero-posterior and lateral projection images were calculated by the maximum intensity projection (MIP) algorithm, the standard deviation projection (SD) algorithm and the summed voxel projection (SUM) algorithm. The projection images were compared with 2D whole-body images for visualizing foci. The focal uptakes of various positions in original whole-body PET data (294-392 transaxial images) were visualized on only two MIP reformatted images when superimposition of hot spots did not occur. Even if one hot spot was superimposed over the other hot spot, we could recognize the existence of at least one focus and determine the true positions of the hot spots from corresponding transaxial images. The SD image was found inferior for showing a contrast of small foci to the corresponding MIP images in the neck, mediastinum and abdomen. The SUM image failed to visualize many metastatic lesions. MIP is a promising technique for the easy preliminary assessment of tumor distribution in oncologic whole-body PET study.

Algorithms↗

Spinal projections from the lower brain stem in the cat as demonstrated by the horseradish peroxidase technique. II. Projections from the dorsolateral pontine tegmentum and raphe nuclei.

The descending projections to the spinal cord arising from the dorsolateral pontine tegmentum and brain stem raphe nuclei have been investigated by means of the horseradish peroxidase (HRP) technique. Particular attention was taken to clarify the cells of origin and the funicular trajectory of these spinal projections. After injections of HRP into the spinal cord, a significant of HRP labeled neurons were observed in the following dorsolateral pontine tegmental structures: (1) an area ventral to the nucleus cuneiformis; (2) principal locus coeruleus; (3) locus coeruleus a; (4) locuse subcoeruleus; (5) Kölliker-Fuse nucleus; and (6) nucleus parabrachialis lateralis. As a rule, the projections are ipsilateral and descendaphe-spinal projections, we have demonstrated that the nucleus raphe dorsalis also sends axons to the cervical segment of the spinal cord. Furthermore, in accord with previous reports, HRP labeled cells were also identified in the nucleus raphe magnus, pallidus and obscurus, but not in the nucleus raphe centralis superior and pontis. On the whole the present study further clarified the organization of spinal projections from the dorsolateral pons and raphe nuclei and provided some additional anatomical data for the physiology of the tegmentospinal and raphe-spinal projections.

Animals↗

The corticotrigeminal projection in the cat. A study of the organization of cortical projections to the spinal trigeminal nucleus.

The projection from the cerebral cortex to the spinal trigeminal nucleus has been studied light microscopically in adult cats. Both orthograde degeneration and orthograde intra-axonal labeling techniques have been applied. Our results indicate that the projection from the coronal gyrus (face area of primary somatosensory cortex) to the spinal trigeminal complex is somatotopically organized. In subnucleus caudalis this somatotopy is organized dorsoventrally and appears to match the somatotopic distribution of the divisional trigeminal afferents. Hence cortical fibers originating from the posterior coronal gyrus (upper representation) project ventrolaterally into caudalis where division I trigeminal afferents terminate. Likewise cortical fibers from the anterior coronal gyrus (jaw and tongue representation) terminate dorsomedially in caudalis to overlap with division III trigeminal afferents. In contrast, the distribution of corticofugal afferents to the rostral spinal trigeminal subnuclei (pars interpolaris and oralis) is organized mediolaterally. Therefore in these subnuclei the cortical projection does not appear to overlap the dorsoventral lamination of the divisional trigeminal afferents. In addition, our results suggest that the cortical projection to subnucleus caudalis includes fibers which terminate in the marginal zone (lamina I) and its extensions into the spinal trigeminal tract (the interstitial cells of Cajal). We have been unable to document a projection from the proreate gyrus to the spinal trigeminal complex.

Animals↗

Afferent projections from the brainstem to the three floccular zones in cats. II. Mossy fiber projections.

Mossy fiber projections from the brainstem to the flocculus were studied following injections of horseradish peroxidase (HRP) into the flocculus and following microinjections of HRP into each of the three zones of the flocculus. It has been found that the flocculus receives mossy fiber projections from 4 main sources. (1) Perihypoglossal nucleus--dense projections originate from discrete areas of the rostral pole of the intercalated nucleus, the ventral part of the prepositus hypoglossal nucleus and the adjacent reticular formation. (2) Vestibular nuclear complex--secondary vestibular fibers come from discrete areas in the vestibular nuclei: the ventromedial and dorsomedial parts of the medial and inferior nucleus, the central area of the superior nucleus, the ventromedial part of the lateral nucleus, the group y and the interstitial nucleus of the vestibular nerve. (3) Medullary reticular formation--the strongest projection of mossy fibers arises from the accessory group of the paramedian reticular nucleus. (4) Pontine reticular formation and raphe nucleus--dense projections originate from a narrow zone which involves the caudal part of the dorsal nucleus of the raphe, the inferior and superior central nucleus of the raphe and the medial part of the nucleus reticularis tegmenti pontis. No clear indication of a different mossy fiber projection from the nuclei in the brainstem to the 3 zones of the flocculus was found.

Afferent Pathways↗

Neurogenesis of ascending supraspinal projection neurons: ipsi- versus contralateral projections.

The present study tests the hypothesis that contralaterally projecting supraspinal projection neurons (SPNs) are generated prior to ipsilaterally projecting SPNs. Neuronal time of origin was determined by injecting pregnant rats with tritiated thymidine on one of embryonic (E) days E12 through E15. In mature offspring of thymidine-treated dams, SPNs in the lumbar cord were retrogradely labelled with True Blue delivered at the site of a hemisection in spinal segment C3. Ipsi and contralaterally projecting SPNs in laminae I, VII and VIII and the lateral spinal nucleus, which are known to give rise to long sensory pathways, were generated simultaneously throughout their neurogenic period (E12-E14), while ipsilaterally projecting SPNs in lamina IV and the nucleus dorsalis, which give rise to short sensory pathways, completed neurogenesis one day later (E15). Results suggest that the projection target and its distance from the nerve cell body of origin are more consistent correlates of the duration of the neurogenic period than the course of the axon.

Animals↗

Relating outcomes to processes of care: the Maryland Hospital Association's Quality Indicator Project (QI Project).

BACKGROUND: The Maryland Hospital Association's Quality Indicator Project (QI Project) is a program of indicator development and application that has grown from 7 hospitals in 1987 to more than 700 hospitals today. METHODOLOGY: Expert panels help to create sets of indicators that describe events involved in a specific sequence of patient care. Each hospital collects data elements for the 21 indicators on a quarterly basis using specifically designed data-collection software. Indicator data are adjusted for case complexity, risk of adverse outcomes, and patient group characteristics. A report is developed that states the rate of occurrence of each indicator and how the hospital's indicator rate compares to other hospitals in the database. Hospitals then use this information to determine if specific processes in their delivery of care yield results that deviate from those of other hospitals. The QI Project promotes regional sharing of information about specific hospital initiatives that might benefit other participants. It also provides a model to use in interpreting what the indicator data reveal about hospital performance. OPERATIONAL ISSUES: QI Project is testing process indicators for patient-level and service-level data to supplement current aggregate-level trend and profile analysis. Indicator data are shared solely with participating systems, but changes in the confidentiality policy are being studied. Reliability assessment surveys are periodically conducted. EXAMPLES: Case studies portray improvement of processes prompted by indicator data for unscheduled admission following ambulatory surgery, for surgical wound infections, and for reducing emergency room waiting times. CONCLUSIONS: The chief contribution of the QI Project and similar projects may not be that they identify all issues of quality, but rather that they may help develop a generation of hospital professionals who will be better able to quantify, evaluate, and improve health care quality.

Confidentiality↗

Retinal projections in the freshwater butterfly fish, Pantodon buchholzi (Osteoglossoidei). II. Differential projections of the dorsal and ventral hemiretinas.

Pantodon buchholzi, the freshwater butterfly fish, is a member of the Osteoglossomorpha, the most primitive of the four major teleost radiations. The projections of fibers originating in the dorsal and ventral hemiretinas in Pantodon, as determined with autoradiography, are reported here. Fibers originating in the ventral hemiretina reach their targets through the axial, medial and dorsal optic tracts. Fibers that originate in the dorsal hemiretina reach their points of termination by way of the axial, medial and ventral optic tracts. Projections of the various tracts to preoptic, thalamic, tubercular, pretectal and tectal regions, as described in the previous study of total retinal projections, were verified. The retinal projections to the preoptic, thalamic and tubercular nuclei do not map topographically. Ventral hemiretinal fibers are mapped, however, onto the dorsal part of the nucleus pretectalis superficialis pars parvocellularis, the rostral part of the dorsal accessory optic nucleus, the entire nucleus pretectalis periventricularis pars ventralis and the dorsomedial portion of the optic tectum. Ventral hemiretinal fibers also supply most if not all the retinal innervation to the central pretectal nucleus. In contrast, dorsal hemiretinal fibers are mapped onto the ventral part of nucleus pretectalis superficialis pars parvocellularis, the entire dorsal accessory optic nucleus and the ventrolateral portion of the optic tectum. The dorsal and ventral hemiretinal projections to the tectum about at a cytoarchitectonically recognizable point, indicating that no discontinuity is present in the retinal connectivity with the tectum. The pars parvocellularis of nucleus pretectalis superficialis is a simple, unfolded, and nonlaminar structure in Pantodon. This structure contrasts markedly with the more complex, folded structure of the nucleus in the majority of other examined teleosts. The orientation of the projections from the dorsal and ventral hemiretinas onto this nucleus in Pantodon is congruent with that seen in other fishes only after a schematic unfolding of the nucleus in these fishes.

Animals↗

Notice of availability of funding for alternative projects, known as Wilson/Fish Projects, to implement alternative means of providing interim financial assistance, medical assistance, social services, and case management to refugees and Cuban and Haitian entrants. Office of Refugee Resettlement (ORR), ACF, DHHS.

The Office of Refugee Resettlement (ORR) announces that competing applications will be accepted from public and private non-profit organizations under a standing announcement for Wilson/Fish projects which propose alternative approaches to serving refugees. The purpose of an alternative project is to provide integrated services and cash assistance to refugees in order to increase refugees' prospects for early employment and self-sufficiency, reduce their level of welfare dependence, enhance acculturation, and promote coordination among voluntary resettlement agencies and service providers. Projects will be accepted under either of two categories: (1) Projects to establish or maintain a refugee program in a State where the State is not participating in the refugee program or is dropping out of the refugee program or a portion of the program; and (2) projects to provide an alternative to the existing system of assistance and services to refugees. Funding is available to these projects under the "Wilson/Fish" authority.

Cuba↗