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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

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

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

Noradrenergic projections to brainstem nuclei: evidence for differential projections from noradrenergic subgroups.

Retrograde transport of the fluorescent tracer True Blue was used in combination with immunohistochemical staining of dopamine-beta-hydroxylase (a marker protein for noradrenergic neurons) to determine the origin of noradrenergic projections to three cranial nerve nuclei: 1) the motor nucleus of the trigeminal nerve, 2) the motor nucleus of the facial nerve, and 3) the spinal trigeminal nucleus pars interpolaris. Noradrenergic cells in the rat brainstem were divided into subgroups and their numbers were determined in serial sections stained with an antiserum to rat dopamine-beta-hydroxylase. Following tracer injections into the three brainstem nuclei, retrogradely labeled noradrenergic neurons were counted and the percentage of True Blue-labeled noradrenergic cells in each subgroup was calculated. Injections of tracer into the three cranial nerve nuclei resulted in distinctly different labeling patterns of noradrenergic cells. Of the total number of norepinephrine neurons projecting to the motor nucleus of the trigeminal nerve, 68% were observed within the A7 cell group; 75% of those innervating the motor nucleus of the facial nerve were found in the A5 cell group, and 65% of those projecting to the spinal trigeminal nucleus pars interpolaris were present in the locus ceruleus and subceruleus. These findings indicate that norepinephrine cells in the rat brainstem do not constitute a homogeneous population of cells but that several discrete systems can be identified that differ not only in topography but also in the terminal distribution of their axons. This combined retrograde transport-immunohistochemical study reveals a much higher degree of topographic order in the projections of norepinephrine neurons than has previously been recognized. The observation of differential projections of noradrenergic subgroups argues against the notion of a global influence of these cells over functionally diverse areas of the brainstem.

Animals

Extrinsic projections from area CA1 of the rat hippocampus: olfactory, cortical, subcortical, and bilateral hippocampal formation projections.

Hippocampal area CA1 provides the major cortical output of the hippocampus, but only its projections to the subiculum and lateral septal nucleus are well characterized. The present study reexamines these extrinsic projections by using anterograde and retrograde tracing techniques. Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in the septal one-third of CA1 label axons and terminals in subicular, postsubicular, retrosplenial, perirhinal, and entorhinal cortices, lateral septal nucleus, and diagonal band of Broca. The septal CA1 injections also label terminal fields in contralateral CA1, and in contralateral subicular, postsubicular, perirhinal, and entorhinal cortices. Injections into the splenial one-third of CA1 label axons and terminals in subiculum, postsubiculum, ventral area infraradiata, and lateral septal nucleus, but they do not label axons and terminals on the contralateral side of the brain. Injections in the temporal one-third of CA1 label axons and terminals in subicular, parasubicular, entorhinal, and infraradiata cortices, anterior olfactory nucleus, olfactory bulb, lateral septal nucleus, nucleus accumbens, amygdala, and hypothalamus. The temporal CA1 injections label no axons on the contralateral side of the brain. These data demonstrate that CA1 has more widespread projections than previously appreciated, and they provide the first clear evidence that CA1 projects to the contralateral cortex and to the ipsilateral olfactory bulb, amygdala, and hypothalamus. The results also demonstrate a heterogeneity in the efferent projections originating in different septotemporal levels of CA1.

Afferent Pathways

Distribution and origins of substance P-immunoreactive projections to the paraventricular and supraoptic nuclei: partial overlap with ascending catecholaminergic projections.

Anatomical and pharmacological evidence suggests a role for substance P (SP) in the control of vasopressin secretion, but the origins of SP-immunoreactive (IR) projections to the paraventricular (PVH) and supraoptic (SO) nuclei of the hypothalamus have not yet been identified. Combined axonal transport, immunohistochemical, and ablation approaches were used to characterize the organization of SP-IR projections to the PVH. The results may be summarized as follows: (1) SP-IR projections are broadly and prominently distributed throughout the SO and both the magnocellular and parvicellular divisions of the PVH. The distribution within the PVH is quite uniform. (2) Combined retrograde transport-immunohistochemical analyses identified multiple potential sources of SP-IR inputs to the PVH. These included a number of hypothalamic cell groups, the laterodorsal and peduculopontine tegmental nuclei, and the rostral and caudal aspects of the ventrolateral medulla. Portions of the tegmental and medullary SP-IR neurons that were retrogradely labelled following tracer deposits in the PVH also stained positively for choline acetyltransferase or tyrosine hydroxylase, respectively. (3) To evaluate the distribution and prominence of medullary SP-IR projections to the PVH and SO, staining for SP and catecholamine-synthesizing enzymes was carried out in animals that had previously received knife cuts at the level of the pontomedullary border. Pronounced, and roughly parallel decrements in staining for peptide and amines were seen in the magnocellular division of the PVH and in the SO; less marked reductions in SP-IR varicosities are in a position to influence multiple visceral regulatory cell types in the PVH and SO. Inputs to the magnocellular neurosecretory system arise in large measure from medullary neurons in which SP coexists with catecholamines. SP-IR projections to the parvicellular division of the PVH appear to originate from a number of sources.

Amino Acid Sequence

Axon extension and retraction by leech neurons: severing early projections to peripheral targets prevents normal retraction of other projections.

During leech embryogenesis, interactions between homologous neurons in neighboring segments lead to the selective retraction of longitudinal axonal projections by midbody AP and AE neurons, which maintain lateral axonal projections to the periphery. Results of experiments reported here show that disconnecting the lateral projections from the periphery rescues the projections normally fated to retract. We propose that these neurons normally progress through two states during early development, one in which they are insensitive to interactions with their homologs (state A) and a second in which they are sensitive (state B). Establishment of lateral connections with their targets triggers the switch from state A to state B; cutting these projections puts neurons back to state A.

Animals

Two projection computed tomography: the axial and Towne projections.

It is occasionally necessary in evaluating lesions around the third ventricle and posterior fossa to supplement the axial view with another projection. The authors have routinely used the coronal projection as a second projection. However, the Towne view for computed tomography can be used as a second projection instead of the coronal; it is technically easier and faster to perform than the coronal projection, and provided good evaluation of the posterior fossa and para third ventricular areas in children.

Cerebral Ventricle Neoplasms

[Afferent projections to the uvula in the cat. II. Mossy fiber projections].

The mossy fiber projections to the uvula of the cerebellum were studied by means of retrograde axonal transport of horseradish peroxidase (HRP) in the cat. Following large and small injections into the uvula, distribution of the labeled cells in the brainstem nuclei was investigated. The results showed different afferent projections between the dorsal and ventral uvula. Major sources projecting to the dorsal uvula were the peduncular, paramedian, and lateral nuclei of the pontine nuclei. Labeled cells found in the pontine nuclei amounted to 81.6% of the total number of labeled cells in cat 1. On the other hand, major sources projecting to the ventral uvula were the caudal aspect of the medial and inferior vestibular nuclei, the x- and f-groups of the vestibular nuclei, the dorsal and central aspect of the superior vestibular nucleus, the rostral dorsomedial aspect of the paramedian nucleus of the pontine nuclei, the caudal aspect of the prepositus hypoglossal nucleus, and the infratrigeminal nucleus. Labeled cells in the vestibular nuclei amounted to 72.1% of the total number of the labeled cells in the cat 40. It was revealed that the lateral aspect of the ventral uvula receives inputs from the pontine nuclei, whereas the medial part of the ventral uvula receives inputs from the vestibular nuclei. Mediolateral differences were not found in the dorsal uvula. These mossy fiber zones were mediolaterally wide, and the dorsal uvula was different from the ventral uvula with regard to mossy fiber projection.

Afferent Pathways

Separate non-cholinergic descending projections and cholinergic ascending projections from the nucleus tegmenti pedunculopontinus.

A substantial population of cells from the nucleus tegmenti pedunculopontinus was demonstrated to have descending projections to the spinal cord using fluorescent retrograde axonal tracers. Double-labeling studies showed that separate perikarya in this region have descending versus ascending projections. The distributions of the cell bodies with ascending or descending projections were spatially distinct, but partially overlapping. Some ascending, but not the descending, projections were cholinergic.

Acetylcholine

Corticonuclear and corticovestibular projections from the uvula in the albino rat: differential projections from sublobuli of the uvula.

The organization of the corticonuclear and corticovestibular projections from the uvula was investigated in the albino rat by an autoradiographic method. The corticonuclear fibers from sublobule a of the uvula terminated in the caudoventral part of the medial cerebellar nucleus, and the caudomedial part of the posterior interpositus nucleus with mediolateral topography. The medial and lateral portions of the sublobule projected to the medial cerebellar and posterior interpositus nuclei, respectively. The corticovestibular fibers from sublobule a terminated in the dorsal and rostral parts of the superior vestibular nucleus, the dorsal part of the lateral vestibular nucleus, and the caudomedial part of the spinal vestibular nucleus. However, the corticonuclear fibers from sublobuli b and c of the uvula terminated additionally in the ventromedial part of the lateral cerebellar nucleus, while the corticovestibular fibers from these sublobuli terminated additionally in the subnucleus y of the vestibular complex, with probable termination in the medial vestibular nucleus. The cortical region which sent efferent projections to the ventromedial part of the lateral cerebellar nucleus and the subnucleus y was located laterally in sublobuli b and c of the uvula. These differential projection patterns from the dorsal and ventral sublobuli suggest the difference of the functional correlates between the sublobuli in the uvula.

Animals

Neurons in the sacral parasympathetic nucleus that project to the hypothalamus do not also project through the pelvic nerve--a double labeling study combining Fluoro-gold and cholera toxin B in the rat.

We recently reported that neurons in the sacral parasympathetic nucleus (SPN) project directly to the hypothalamus. In the present study, we examined the possibility that individual neurons in SPN send both an axon into the pelvic nerve and an ascending projection to the hypothalamus. We used a new double-labeling technique in which two sensitive retrograde tracers (Fluoro-gold and cholera toxin subunit B immunocytochemically stained with rhodamine-labeled antibodies) were combined. The effectiveness of this combination for singly and doubly labeling neurons was established in experiments in which both tracers were injected into overlapping areas of the tongue or ventrobasal thalamus. These injections doubly labeled large numbers of neurons in the hypoglossal or dorsal column nuclei, respectively. In studies of the projections of neurons in the SPN, injection of one tracer into the hypothalamus and the other into the pelvic nerve and/or pelvic ganglion singly labeled many neurons (more than 3300 in the 7 examined cases). However, no SPN neurons were doubly labeled. These findings indicate that the SPN in the rat consists of at least two distinct groups of cells, parasympathetic preganglionic neurons and neurons that project to the hypothalamus.

Animals

The Imo State (Nigeria) Drinking Water Supply and Sanitation Project, 1. Description of the project, evaluation methods, and impact on intervening variables.

A health impact evaluation was conducted in conjunction with the Imo State Drinking Water Supply and Sanitation Project in Nigeria. The project consisted of a package of water supply, sanitation, and health and hygiene education given by village-based workers. The evaluation was a quasi-experimental study covering pre-, peri- and post-intervention periods. Data were collected from 3 intervention and 2 control villages. Baseline surveys indicated that the intervention and control areas were similar with respect to most socio-demographic variables. Use of the improved water supply was high, although this was influenced by borehole-to-population ratios and household-to-borehole distances. Water collection time was consequently greatly reduced. Data from a small sample of households showed that borehole water became heavily contaminated during collection and storage, and that there was no significant change in consumption of water per person. Adults in 46% of household units in the intervention area were using ventilated improved pit latrines by the end of the study period. Use by young children (2-5 years old), however, was low. Limitations in the success of the health education component of the project were found. Although changes were found in knowledge, attitudes and practices related to water and sanitation, and in management of childhood diarrhoea, this occurred in both the intervention and control areas.

Health Education

Development of the olivocerebellar projection in the rat: II. Matching of the developmental compartmentations of the cerebellum and inferior olive through the projection map.

A transient biochemical parcellation has been observed by immunocytochemical methods, during the perinatal development of both the inferior olive and the cerebellum. In the present study, we sought a relationship between this developmental compartmentation and the organization of the olivocerebellar projection. In the inferior olive, a transient parvalbumin immunoreactivity restricted to the dorsal cap of the medial accessory olive is observed around birth. The climbing fiber projection of the dorsal cap was identified in the cerebellum of newborn rats based on its parvalbumin immunoreactivity. The pattern of this projection, restricted to lobules IX and X of the vermis, and to the flocculus, is indistinguishable from that of the adult medial accessory olive, which was previously described from axonal tracing experiments. The parvalbumin immunoreactive climbing fibers were followed between birth and postnatal day 7. In the caudal vermis, Purkinje cell subpopulations can be identified between embryonic day 20 and postnatal day three, on the basis of their differential immunostaining with an antibody directed against a specific peptide, PEP 19. In lobule X, the parvalbumin immunoreactive climbing fibers form two sagittal bands on each side of the midline, one medial and one lateral. The medial parvalbumin immunoreactive climbing fiber band is coextensive with a PEP 19 negative Purkinje cell cluster, indicating a clear relationship between the biochemical parcellations of the cerebellum and inferior olive.

Animals

Modification of the projection from the sensory cortex to the motor cortex following the elimination of thalamic projections to the motor cortex in cats.

Examination of the projection from area 2 of the sensory cortex to the motor cortex revealed substantial changes following lesion of the ventrolateral nucleus of the thalamus. These observed changes were as follows. (1) The polarity of the evoked potentials elicited by area 2 stimulation reversed in the depth of the motor cortex whereas in normal animals, there was no reversal. (2) The amplitude of area 2-elicited EPSPs in the motor cortical neurons became greater following the lesion of VL. (3) The shape of the observed EPSPs was characterized by multiple peaks whereas in normal animals, the EPSPs were generally smooth and monophasic. (4) Neurons receiving a short-latency input from area 2 were distributed throughout the depths of the motor cortex whereas in normal animals, they were located only in the upper layers (layers II and III). (5) Intracellular injection of HRP revealed that the neurons receiving short-latency input were not restricted to typical stellate type cells, but also included bipolar or bitufted neurons with elongated cell bodies and polarized arborizations. These neurons were located in the superficial (II and III) as well as in the deep (V) layer. It is concluded that the elimination of thalamic input resulted in the reinforcement of the corticocortical input to the motor cortex. The subsequently observed corticocortical projection extended to neurons did not originally innervated by the association fibers. The results suggested that functional recovery following thalamic lesion is partly due to reorganization of projections from the sensory cortex to the motor cortex.

Animals

The effects of a finite number of projection angles and finite lateral sampling of projections on the propagation of statistical errors in transverse section reconstruction.

The dependence of noise amplification on the nuber of projection angles and on the lateral sampling interval of projections is presented. It is shown that about 1-5D/d angles and a sampling interval of about 0-5d are required in order that the data be efficiently utilized. D is the linear dimension of the reconstruction region and d is the linear dimension of the cells into which the reconstruction region is subdivided (resolution length). Values for noise amplification are given for various combinations of projection angles and lateral sampling intervals.

Information Theory

[The long-term evaluation of a project for the primary prevention of coronary cardiopathy at 10 years from the stopping of treatment. The second phase of the Roman Project to Prevent Coronary Cardiopathy (PPCC II Phase)].

At the end of the Rome Project of Coronary Heart Disease (CHD) Prevention (PPCC) lasted 6 years and involving 3131 treated and 2896 control men aged 40-59 belonging to occupational groups, the mean values of some coronary risk factors (systolic blood pressure, serum cholesterol, smoking habits, body mass index) were favourably reduced in treated men as compared to controls. Incidence (-25.4%) and mortality (-26.8%) from CHD were also lower, in 6 years, in treated vs control groups. Ten years after the end of the project and of the treatment procedures in "treated men", a subgroup of 1013 former treated men and one of 843 former controls could be re-examined, whereas mortality data could be collected in those 3395 men who were examined at the end of the 6-year project. The 16 year examination showed that serum cholesterol, blood pressure, body mass index and cigarette consumption are now lower, on the average, in former control men, as compared to that of former treated ones. The finding is largely justified by different behaviours of eating, smoking and motion habits and by the motivation and behaviour toward health problems. Coronary mortality, during the last 10 years, was higher among the former treated men as compared to that of former control men (+50.0%; p less than 0.05%). The reverse trend observed in these 10 years is likely explained by a psychological "rebound" phenomenon occurred in the former treated men and to some beneficial effects, in the former control men, bound to the secular trend which presently characterizes some living habits of the Italian population.

Cause of Death

Familial insulin-dependent diabetes mellitus (IDDM) epidemiology: standardization of data for the DIAMOND Project. The WHO Multinational Project for Childhood Diabetes Group.

The WHO Multinational Project for Childhood Diabetes, known as the DIAMOND Project, has been responsible for establishing insulin-dependent diabetes mellitus (IDDM) registries and for carrying out diabetes incidence studies, descriptive epidemiological research, and analytical investigations which are being used to test specific hypotheses regarding the etiology of the disease. Standardized epidemiological data are being collected from countries around the world, permitting international comparisons between registries. Multinational studies are also beginning to investigate the potential genetic determinants of the disease, and are contributing to the development of familial IDDM epidemiology worldwide. The development of standards for data collection of IDDM family histories is important for multinational studies of IDDM recurrence risks in families, descriptive analyses of patterns of familial aggregation, and comparative analytical investigations of specific etiological determinants of IDDM in relatives. These activities are being implemented through the DIAMOND Project.

Child