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PubMed1984

Recovery of the ipsilateral oculotectal projection following nerve crush in the frog: evidence that retinal afferents make synapses at abnormal tectal locations.

The ipsilateral oculotectal projection in the frog is a topographic mapping of the binocular part of the visual field of one eye on the ipsilateral tectal lobe. The underlying neuronal circuitry consists of the topographic, crossed retinotectal projection and an intertectal pathway which relays information from a given point in one tectal lobe to the visually corresponding point in the other. During optic nerve regeneration, there is a period when the terminals of retinotectal afferents are found at abnormal locations in the opposite tectal lobe. Whether they form functional synapses at this time is not known. If so, one would expect to observe correlated abnormalities in the ipsilateral oculotectal projection. To determine whether such abnormalities exist, we have made parallel electrophysiological studies of the recovery of the retinotectal and ipsilateral oculotectal projections following crush of one optic nerve. The earliest stage of recovery was characterized by a lack of significant topographic order in the retinotectal projection and by the absence of a physiologically observable ipsilateral projection. Within a short time, the retinotectal projection became topographically organized and a similarly organized ipsilateral projection appeared. While topographic, the retinotectal projection at intermediate times was abnormal in that the multiunit receptive fields recorded at individual tectal loci were greatly enlarged. Multiunit receptive fields were similarly enlarged in the ipsilateral projection. In addition, some ipsilateral fields included areas of visual space not normally represented in the projection. The abnormalities in both projections subsequently disappeared over the same time course. Throughout recovery there was a high correlation between multiunit receptive field sizes in the contralateral tectal lobe and those at visually corresponding points in the ipsilateral tectal lobe. Enlarged multiunit receptive fields in the contralateral tectal lobe could not be accounted for in terms of optical or retinal abnormalities since single unit receptive field sizes were normal. Nor could they be accounted for in terms of changes in recording characteristics since simultaneously recorded fields activated by the undisturbed eye were normally sized. We conclude that the enlarged fields in the contralateral tectal lobe indicate the presence at individual tectal loci of afferents from wider than normal retinal regions. Similar considerations ruled out optical, retinal, and recording abnormalities as the explanation for the enlarged multiunit receptive fields in the ipsilateral tectal lobe.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1997

GABAergic presubicular projections to the medial entorhinal cortex of the rat.

We characterized presubicular neurons giving rise to bilateral projections to the medial entorhinal cortex (MEA) of the rat. Retrograde labeling of presubiculo-entorhinal projections with horseradish peroxidase and subsequent GABA immunocytochemistry revealed that 20-30% of the ipsilaterally projecting neurons are GABAergic. No GABAergic projections to the contralateral MEA were observed. GABAergic projection neurons were observed only in the dorsal part of the presubiculum, which, when taking into account the topography of presubicular projections to MEA, indicates that only the dorsal part of MEA receives GABAergic input. The GABAergic projection neurons constitute approximately 30-40% of all GABAergic neurons present in the superficial layers of the dorsal presubiculum. Using double-label fluorescent retrograde tracing, we found that the ipsilateral and contralateral presubiculo-entorhinal projections originate from different populations of neurons. Anterograde labeling of presubiculo-entorhinal projections and electron microscopical analysis of labeled terminals substantiated the presence of a restricted GABAergic presubiculo-entorhinal projection. A small fraction of afferents to only ipsilateral dorsal MEA formed symmetrical synapses with dendritic shafts. No symmetrical synapses on spines were noted. Most afferents to the dorsal part of ipsilateral MEA, as well as all afferents to the remaining ipsilateral and contralateral MEA, formed asymmetrical synapses with both spines and dendritic shafts in an almost equal ratio. Thus, we conclude that the majority of the presubiculo-entorhinal projections exert an excitatory effect on both principal neurons and interneurons. The projections from the dorsal part of the presubiculum comprise a small inhibitory component that originates from GABAergic neurons and targets entorhinal interneurons.

Afferent Pathways↗
PubMed1998

Specific projections of sympathetic preganglionic neurons are not intrinsically determined by segmental origins of their cell bodies.

Sympathetic preganglionic projections of the chick are segmentally specific. Neurons from the 16th cervical (C16) and the first thoracic (T1) spinal cord segments project almost exclusively in the rostral direction, while those from the fifth thoracic (T5) to the first lumbar (L1) spinal segments project almost exclusively in the caudal direction. Neurons from the intervening spinal cord segments (T2-4) project in rostral and caudal directions. There is also a tendency for rostrally located neurons in each segment to project rostrally and caudally located neurons to project caudally. To investigate whether specific projections of preganglionic neurons are intrinsically determined by segmental origins of their cell bodies, neural tube segments were transplanted or rotated in embryos at stages 19-26; these stages include times during and after preganglionic cell birth and just prior to axon outgrowth. When the T1 neural tube segment was replaced with the T5 or T7 neural tube segment the transplanted T5 or T7 preganglionic neurons, now in the T1 position, projected rostrally. Conversely, when the T5 or T7 neural tube segment was replaced with the T1 neural tube, the transplanted T1 preganglionic neurons projected caudally. In addition, when individual T3 spinal cord segments were rotated 180 degrees along the A-P axis, neurons which were originally in the caudal part of the segment projected rostrally, whereas neurons originally from the rostral part of the segment projected caudally. These results show that specific projections of preganglionic neurons are not intrinsically determined by segmental origins of their cell bodies.

Animals↗
PubMed1998

Failure-as-success: multiple meanings of eradication in the Rockefeller Foundation Sardinia project, 1946-1951.

In the history of malaria control programs there were important tensions between proponents of the concept of eradication and those of malaria control. In this debate the concept of eradication has had multiple meanings. This paper concerns the post-hoc interpretations of the outcomes of the Rockefeller International Health Foundation-sponsored project conducted in Sardinia between 1946 and 1951. The Ente Regionale per la Lotta Anti-Anofelica in Sardegna (regional agency for the anti-Anopheles struggle in Sardinia) (ERLAAS) project was conceived as a large-scale, field-based pilot demonstration project to test the feasibility of the strategy of "species eradication" in an area with an endemic malaria vector. Species eradication, a strategy championed by Soper, was aimed at the total annihilation of an anopheline vector from an area. Under the leadership of the Rockefeller Foundation, the ERLAAS project used postwar UNRRA funds to purchase local labor and imported DDT, oil-suspension, and war-surplus equipment in an "all-out" campaign against Anopheles labranchiae, even in sparsely populated areas. The original aim was entirely entomological; species eradication was expected to be completed in two years for a cost of $2.7 million. Ironically, malaria mortality on the island had already been lowered before WWII by a series of public health interventions. The ERLAAS project encountered severe technical and logistical difficulties; its ultimate failure was foreshadowed in the resignation of the first American director who doubted the feasibility of species eradication. Ultimately, the ERLAAS project was ended after four and a half years and an expenditure of $11.2 million. Although new malaria transmission on the island ended the project failed to eliminate A labranchiae. Finally, the regional government was counselled to continue mosquito control efforts; the continuation of a substantial mosquito control program for fifty years after this famous "malaria eradication" project runs contrary to the basic cost/benefit logic of the eradication concept. Nevertheless, in the popular press both in the U.S. and Italy, the project was presented and heralded as a major success in liberating the island from the age-old stranglehold and misery of malaria. In the course of the project, the goals of ERLAAS became transformed from species eradication to malaria eradication; this was an important political spin that was put on the evaluation of the program. The consequences of this tactical change in discourse included two important facts: the contribution of the Rockefeller Foundation to the island was exaggerated, and the legitimacy of the concept of global eradication was maintained. In the framework of the World Health Organization and the agreement for a global malaria eradication program, the "failure" of the Sardinia project was seldom recognized or mentioned. The technical, economic, and logistical problems faced by ERLAAS were very similar to the problems associated with the end of the WHO global malaria eradication policy in 1972. The Sardinia project is presented as a case of "failure-as-success"; an ideological transformation was made, not simply for local political expediency, but more importantly because of the predominance of the modernist cultural model of "progress through technology" that characterized international Public Health in the postwar era.

Animals↗
PubMed1998

Segmental specificity of chick sympathetic preganglionic projections is influenced by preganglionic neurons from neighboring spinal cord segments.

Sympathetic preganglionic neurons of the chick are located between the brachial and lumbosacral enlargements of the spinal cord. Their axons exit the spinal cord via their adjacent ventral roots and project rostrally or caudally along the sympathetic trunk to innervate sympathetic ganglia. The projections of sympathetic preganglionic neurons are segmentally specific. Neurons from the 16th cervical (C16) and the first thoracic (T1) spinal cord segments project predominantly in the rostral direction, whereas those from the fifth thoracic (T5) to the first lumbar (L1) spinal segments project predominantly in the caudal direction. Neurons from intervening spinal cord segments (T2-T4) project in rostral and caudal directions. In the present study, neural tube manipulations show that the direction of preganglionic projections is altered by both the elimination and addition of preganglionic neurons projecting into the sympathetic trunk from neighboring segments. The present study also compares the projections of preganglionic neurons from transplants of multiple neural tube segments with those from transplants of single neural tube segments reported in a previous study (Yip, 1987). In the previous study when single thoracic neural tube segments were transplanted to the cervical level, preganglionic neurons did not maintain their original projection patterns. The present study found that, when contiguous neighboring segments were transplanted to the cervical level, preganglionic neurons maintained projection patterns characteristic of their original segmental levels. These results indicate that the direction of preganglionic projections can be influenced by neurons from neighboring segments, suggesting that the formation of segmentally specific preganglionic projections during embryogenesis may involve the interactions of preganglionic neurons with those from neighboring spinal cord segments.

Adrenergic Fibers↗
PubMed2005

Consumer involvement in Quality Use of Medicines (QUM) projects - lessons from Australia.

BACKGROUND: It is essential that knowledge gained through health services research is collated and made available for evaluation, for policy purposes and to enable collaboration between people working in similar areas (capacity building). The Australian Quality Use of Medicine (QUM) on-line, web-based project database, known as the QUMmap, was designed to meet these needs for a specific sub-section of health services research related to improving the use of medicines. Australia's National Strategy for Quality Use of Medicines identifies the primacy of consumers as a major principle for quality use of medicines, and aims to support consumer led research. The aim of this study was to determine how consumers as a group have been represented in QUM projects in Australia. A secondary aim was to investigate how the projects with consumer involvement fit into Australia's QUM policy framework. METHOD: Using the web-based QUMmap, all projects which claimed consumer involvement were identified and stratified into four categories, projects undertaken by; (a) consumers for consumers, (b) health professionals for consumers, (c) health professionals for health professionals, and (d) other. Projects in the first two categories were then classified according to the policy 'building blocks' considered necessary to achieve QUM. RESULTS: Of the 143 'consumer' projects identified, the majority stated to be 'for consumers' were either actually by health professionals for health professionals (c) or by health professionals for consumers (b) (47% and 40% respectively). Only 12 projects (9%) were directly undertaken by consumers or consumer groups for consumers (a). The majority of the health professionals for consumers (b) projects were directed at the provision of services and interventions, but were not focusing on the education, training or skill development of consumers. CONCLUSION: Health services research relating to QUM is active in Australia and the projects are collated and searchable on the web-based interactive QUMmap. Healthcare professionals appear to be dominating nominally 'consumer focussed' research, with less than half of these projects actively involving the consumers or directly benefiting consumers. The QUMmap provides a valuable tool for policy analysis and for provision of future directions through identification of QUM initiatives.

Australia↗
PubMed1996

Central projections and somatotopic organisation of trigeminal primary afferents in pigeon (Columba livia).

Injections of cholera toxin B-chain conjugated to horseradish peroxidase into individual peripheral branches of the trigeminal nerve or into the trigeminal ganglion showed that an ascending trigeminal tract (TTA) terminated in distinct ventral and dorsal divisions of the principal sensory nucleus (PrVv and PrVd, respectively), and a descending tract (TTD) terminated within pars oralis, pars interpolaris, and pars caudalis divisions of the nucleus of TTD (nTTD) and within the dorsal horn of the first six cervical spinal segments. In PrVd, mandibular, ophthalmic, and maxillary projections were predominantly located dorsally, ventrally, and medially, respectively. In nTTD, mandibular projections lay dorsomedially, ophthalmic projections lay ventrolaterally, and maxillary projections lay in between. At caudal medullary and spinal levels, mandibular projections were situated medially, ophthalmic projections were situated laterally, and maxillary projections were situated centrally. The terminations within the dorsal horn were most dense in laminae III and IV and were least dense in lamina II, with laminae III-IV also receiving topographically organised contralateral projections. Extratrigeminal projections were mainly to the external cuneate nucleus by way of a lateral descending trigeminal tract (lTTD; Dubbeldam and Karten [1978] J. Comp. Neurol. 180:661-678) and to the region of the tract of Lissauer and lamina I of the dorsal horn. Other projections were to a region medial to the apex of pars interpolaris, to the nuclei ventrolateralis anterior (Vla) and presulcalis anterior (Pas) of the solitary complex, and sparsely to the lateral reticular formation (plexus of Horsley) ventral to TTD. No projections were seen to the trigeminal motor nuclei or to the cerebellum.

Afferent Pathways↗
PubMed1996

Neurofilament protein is differentially distributed in subpopulations of corticocortical projection neurons in the macaque monkey visual pathways.

Previous studies of the primate cerebral cortex have shown that neurofilament protein is present in pyramidal neuron subpopulations displaying specific regional and laminar distribution patterns. In order to characterize further the neurochemical phenotype of the neurons furnishing feedforward and feedback pathways in the visual cortex of the macaque monkey, we performed an analysis of the distribution of neurofilament protein in corticocortical projection neurons in areas V1, V2, V3, V3A, V4, and MT. Injections of the retrogradely transported dyes Fast Blue and Diamidino Yellow were placed within areas V4 and MT, or in areas V1 and V2, in 14 adult rhesus monkeys, and the brains of these animals were processed for immunohistochemistry with an antibody to nonphosphorylated epitopes of the medium and heavy molecular weight subunits of the neurofilament protein. Overall, there was a higher proportion of neurons projecting from areas V1, V2, V3, and V3A to area MT that were neurofilament protein-immunoreactive (57-100%), than to area V4 (25-36%). In contrast, feedback projections from areas MT, V4, and V3 exhibited a more consistent proportion of neurofilament protein-containing neurons (70-80%), regardless of their target areas (V1 or V2). In addition, the vast majority of feedback neurons projecting to areas V1 and V2 were located in layers V and VI in areas V4 and MT, while they were observed in both supragranular and infragranular layers in area V3. The laminar distribution of feedforward projecting neurons was heterogeneous. In area V1, Meynert and layer IVB cells were found to project to area MT, while neurons projecting to area V4 were particularly dense in layer III within the foveal representation. In area V2, almost all neurons projecting to areas MT or V4 were located in layer III, whereas they were found in both layers II-III and V-VI in areas V3 and V3A. These results suggest that neurofilament protein identifies particular subpopulations of corticocortically projecting neurons with distinct regional and laminar distribution in the monkey visual system. It is possible that the preferential distribution of neurofilament protein within feedforward connections to area MT and all feedback projections is related to other distinctive properties of these corticocortical projection neurons.

Animals↗
PubMed1997

Quantitative analysis of spiral ganglion projections to the cat cochlear nucleus.

A quantitative examination of the tonotopic organization of primary afferent projections to the cochlear nucleus (CN) in adult cats was conducted by using focal extracellular injections of Neurobiotin (NB) into the spiral ganglion of the basal cochlea. One to three injections separated by intervals of at least 2 mm were positioned along the basal one-third of the cochlea. Each injection produced discrete projection laminae that appeared as parallel horizontal sheets of labeled axons terminals distributed sequentially dorsally to ventrally across each major CN subdivision: the anteroventral, posteroventral, and dorsal cochlear nucleus, (AVCN, PVCN, and DCN, respectively). The length (rostrocaudal dimension), width (mediolateral dimension), thickness (dorsoventral dimension), and relative placement of 18 "frequency-band" laminae were measured in 10 adult cochlear nuclei. The average AVCN projection thickness was approximately twice that of the PVCN and DCN projections. In double injection cases, the center-to-center separation between AVCN laminae was also approximately twice that in the PVCN and equal to that in the DCN. Lamina thickness did not differ significantly as a function of frequency representation. However, in both width and length, mid-frequency laminae were up to two times larger than high-frequency laminae. Thus, the results indicate that DCN projections are the most discrete (i.e., are the thinnest and have the least overlap between adjacent frequency projections), whereas the AVCN projections are the largest but are as discrete as PVCN projections. In addition, high-frequency projections are smaller and more discrete than mild-frequency projections, which are larger and have greater overlap with adjacent frequency projections.

Animals↗
PubMed1999

Mucosa of the guinea pig gastric corpus is innervated by myenteric neurones with specific neurochemical coding and projection preferences.

The present study identified and characterised myenteric neurones involved in the innervation of the gastric mucosa. We applied retrograde neuronal tracing methods by using the dye DiI (1,1'-didodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorat) in combination with the immunohistochemical demonstration of choline acetyltransferase (ChAT), enkephalin (ENK), neuropeptide Y (NPY), nitric oxide synthase (NOS), substance P (SP), and vasoactive intestinal peptide (VIP). This method showed distinct neurochemical coding of DiI-labelled neurones with projections to the mucosa (mucosa neurones): ChAT/- (indicating the presence of ChAT only, 32%), ChAT/NPY/ +/- VIP (22%), NOS/NPY/ +/- VIP (19%), ChAT/SP/ +/- ENK (12%), NOS/- (indicating the presence of NOS only, 8%), or ChAT/ENK (4.6%). DiI-labelled mucosa neurones did not contain calretinin, serotonin, or somatostatin. All ChAT population had primarily ascending projections, whereas the NOS populations had mainly descending projections. Both were further classified as longitudinally and circumferentially projecting neurones, the latter having projection preferences towards the lesser or greater curvature. All subpopulations exhibited projection preferences. Nitrergic projections primarily arose from cell bodies located at the lesser curvature. ChAT/- projections, which dominated the cholinergic pathway, mainly arose from cell bodies located at the greater curvature. The other major cholinergic pathway with the code ChAT/NPY/ +/- VIP consisted of neurones located mainly at the lesser curvature. The results suggest specific coding of gastric myenteric neurones with projections to the mucosa. Polarised projections consisted of ascending cholinergic and descending nitrergic neurones; the additional presence of NPY/VIP was a prominent feature in both pathways. Chemical coding, polarity, and projection preferences of enteric pathways to the gastric mucosa are remarkably different from those of other regions in the gut.

Animals↗
PubMed1996

Leg proprioceptors of the tobacco hornworm, Manduca sexta: organization of central projections at larval and adult stages.

Organization of the central neuropil of the insect ganglion is characterized in part by a modality-specific layering of afferent projections. This organization has been particularly well described for the central projections of thoracic leg sensory neurons of adult locusts, crickets, and flies. Tactile sensory neurons project into a ventral layer of neuropil, while proprioceptive sensory neurons project into an intermediate layer of neuropil. In order to determine whether a modality-specific layering exists in the CNS of larval Manduca sexta, we have examined the projections of sensory neurons innervating one class of putative proprioceptors, the campaniform sensilla, of the larval metathoracic legs. We find that campaniform sensory neurons of the larval legs have central projection patterns that generally distinguish them from each other and from the tactile sensory neurons. The campaniform projections, however, are not completely segregated from tactile projections in ventral layers of neuropil, as has been described in other insects. By contrast, the projections of campaniform sensory neurons from the adult legs are more extensive and elaborate than their larval counterparts and dramatically different from projections of nearby adult tactile hairs, having extensive arborizations in more dorsal regions of neuropil while those of tactile sensory neurons are restricted to very ventral layers of neuropil. This difference in organization of the afferent projections in larval and adult ganglia may reflect different functions of the leg sensilla and different functions of the legs at the two stages.

Animals↗
PubMed2000

Altered development of visual subcortical projections following neonatal thalamic ablation in the hamster.

Previous research has demonstrated that precise patterns of axonal connectivity often develop during a series of stages characterized by pathfinding, target recognition, and address selection. This last stage involves the focusing of projections to a precisely defined region within the target. Because thalamic projections begin to innervate cortex before the latter stages are reached, these projections may be important in the establishment of adult-like patterns of cortical connectivity. To address this issue, we examined the mature corticopontine and corticospinal projections of visual cortex deprived of early thalamic input by visual thalamic ablation. Although ablations on the day of birth in hamsters did not disrupt the targeting of appropriate subcortical structures by visual cortical axons, they did alter the organization of projections within the basilar pons and spinal cord. The density and spread of visual corticopontine connections in lesioned animals was greatly increased relative to unlesioned animals, suggesting that thalamic afferents are required during address selection, when the topographic specificity of projections is established. To determine whether early visual thalamic ablation increases connectivity by stabilizing an exuberant developmental projection, we examined the normal development of visual corticopontine connections in hamsters ages postnatal days 1-17 (P1-P17). From the earliest ages, visual cortical axons innervate the pontine nucleus in regions specific to their adult projection zones and show progressive growth within these zones. At no time during development do projections exist that are equivalent to the projections found after thalamic ablation, suggesting that removal of thalamic input does not simply stabilize a developmental projection.

Aging↗
PubMed2002

Descending supraspinal pathways in amphibians: III. Development of descending projections to the spinal cord in Xenopus laevis with emphasis on the catecholaminergic inputs.

In developmental stages of the clawed toad, Xenopus laevis, we describe the ontogeny of descending supraspinal connections, catecholaminergic projections in particular, by means of retrograde tracing techniques with dextran amines. Already at embryonic stages (stage 40), spinal projections from the reticular formation, raphe nuclei, Mauthner neurons, vestibular nuclei, the locus coeruleus, the interstitial nucleus of the medial longitudinal fasciculus, the posterior tubercle, and the periventricular nucleus of the zona incerta are well developed. At the beginning of the premetamorphic period (stage 46), spinal projections arise from the suprachiasmatic nucleus, the torus semicircularis, the pretectal region, and the ventral telencephalon. After stage 48, tectospinal and cerebellospinal projections develop, with spinal projections from the preoptic area following at stage 51. Rubrospinal projections are present at stage 50. During the prometamorphic period, spinal projections arise in the nucleus of the solitary tract, the lateral line nucleus, and the mesencephalic trigeminal nucleus. With in vitro double-labeling methods, based on retrograde tracing of dextran amines in combination with tyrosine hydroxylase (TH) immunohistochemistry, we show that at stage 40/41, catecholaminergic (CA) neurons in the posterior tubercle are the first to project to the spinal cord. Subsequently, at stage 43, new projections arise in the periventricular nucleus of the zona incerta and the locus coeruleus. The last CA projection to the spinal cord originates from neurons in the nucleus of the solitary tract at the beginning of prometamorphosis (stage 53). Our data show a temporal, rostrocaudal sequence in the development of the CA cell groups projecting to the spinal cord. Moreover, the early appearance of CA fibers, preterminals and terminal-like structures in dorsal, intermediate, and ventral zones of the embryonic spinal cord, suggests an important role for catecholamines during development in nociception, autonomic functions, and motor control at the spinal level.

Aging↗
PubMed2002

Postnatal refinement of auditory nerve projections to the cochlear nucleus in cats.

Studies of visual system development have suggested that competition driven by activity is essential for refinement of initial topographically diffuse neuronal projections into their precise adult patterns. This has led to the assertion that this process may shape development of topographic connections throughout the nervous system. Because the cat auditory system is very immature at birth, with auditory nerve neurons initially exhibiting very low or no spontaneous activity, we hypothesized that the auditory nerve fibers might initially form topographically broad projections within the cochlear nuclei (CN), which later would become topographically precise at the time when adult-like frequency selectivity develops. In this study, we made restricted injections of Neurobiotin, which labeled small sectors (300-500 microm) of the cochlear spiral ganglion, to study the projections of auditory nerve fibers representing a narrow band of frequencies. Results showed that projections from the basal cochlea to the CN are tonotopically organized in neonates, many days before the onset of functional hearing and even prior to the development of spontaneous activity in the auditory nerve. However, results also demonstrated that significant refinement of the topographic specificity of the primary afferent axons of the auditory nerve occurs in late gestation or early postnatal development. Projections to all three subdivisions of the CN exhibit clear tonotopic organization at or before birth, but the topographic restriction of fibers into frequency band laminae is significantly less precise in perinatal kittens than in adult cats. Two injections spaced > or = 2 mm apart in the cochlea resulted in labeled bands of projecting axons in the anteroventral CN that were 53% broader than would be expected if they were proportional to those in adults, and the two projections were incompletely segregated in the youngest animals studied. Posteroventral CN (PVCN) projections (normalized for CN size) were 36% broader in neonates than in adults, and projections from double injections in the youngest subjects were nearly fused in the PVCN. Projections to the dorsal division of the CN were 32% broader in neonates than in adults when normalized, but the dorsal CN projections were always discrete, even at the earliest ages studied.

Aging↗
PubMed2001

Organization of cerebellar and area "y" projections to the nucleus reticularis tegmenti pontis in macaque monkeys.

Axonal projections to the nucleus reticularis tegmenti pontis (RTP) were studied in 11 macaque monkeys by mapping axonal degeneration from lesions centered in the dentate and interpositus anterior (IA) nuclei and by mapping anterograde transport of tritiated amino acid precursors injected into the dentate nucleus. Projections from the dentate and IA nuclei overlap in central parts of the body of RTP, but the terminal field of dentate axons extends dorsomedial and rostral to the terminal field of IA axons, and IA terminal fields extend more ventrolaterally. A caudal to rostral topography of projections from each nucleus onto dorsal to ventral parts of RTP was seen. Projections from rostral parts of both nuclei terminate in a sublemniscal part of the nucleus. The topography of dentate and IA projections onto central to ventrolateral RTP appears to match somatotopic maps of these cerebellar nuclei with the somatotopic map of projections to RTP from primary motor cortex. Projections from caudal and ventral parts of the dentate nucleus appear to overlap oculomotor inputs to rostral, dorsal, and medial RTP from the frontal and supplementary eye fields, the superior colliculus, and the oculomotor region of the caudal fastigial nucleus. Projections to the paramedian part of RTP from vestibular area "y" were also found in two cases that correlated with projections to vertical oculomotor motoneurons. The maps of dentate and IA projections onto RTP correlate predictably with maps of dentate and IA projections to the ventrolateral thalamus and subnuclei of the red nucleus that were made from these same cases (Stanton [1980b] J. Comp. Neurol. 192:377-385).

Afferent Pathways↗
PubMed2001

Number, origins, and chemical types of rat pallidostriatal projection neurons.

The dorsal globus pallidus (GP) receives major inputs from the dorsal neostriatum (Str), the subthalamic nucleus (STN) and the dorsal thalamus. The GP projects to multiple basal ganglia nuclei. One of the GP projection sites is the Str. The pallidostriatal projection has been considered minor. However, several recent studies have suggested that this projection is heavier than previously thought and that it might play a significant role in controlling the activity of the Str. To reveal more details of this projection, we examined the number of GP neurons that participated in the projection, their origins in the GP and their immunoreactivity for the calcium binding protein parvalbumin (PV), by using a combination of Fluoro-Gold (FG) retrograde labeling and immunohistochemical methods. Immunostaining for the calcium binding protein calbindin-28K (CaBP) was used to identify the CaBP-poor sensorimotor and CaBP-rich associative Str regions and the corresponding CaBP-poor middle, CaBP-rich border, and the caudomedial GP regions. The CaBP-poor dorsolateral Str region occupies a small portion of the Str, whereas the CaBP-poor middle GP region occupies a large portion of the GP. The immunostaining for neuron-specific nuclear protein (NeuN) was used to visualize neurons that were immunonegative for FG or PV. Cell counts revealed that the middle GP region contained a higher density of neurons and also a higher percentage of PV-positive neurons than the border and caudomedial regions of the GP. These observations suggested that the GP is involved more in sensorimotor function than associative function. Approximately 40% of neurons in the CaBP-poor middle GP region project to the CaBP-poor part of the dorsolateral Str. Approximately 30% of the neurons in both the CaBP-rich border and the caudomedial GP regions project to the CaBP-rich Str region. More than 40% of the pallidostriatal neurons in CaBP-poor middle GP region are PV-positive, whereas most of those in CaBP-rich GP regions are PV-negative. It was estimated from the cell count data that most of the PV-negative neurons in all three regions of the GP project to the Str. The results indicate that the sensorimotor and associative territories of the Str have reciprocal projections between corresponding territories of the GP. The involvement of a large number of GP neurons suggested that the pallidostriatal projection should be taken into account in the analysis of functional roles of the basal ganglia.

Animals↗
PubMed2004

Bilateral corticospinal projections arise from each motor cortex in the macaque monkey: a quantitative study.

The corticospinal projection is considered to influence fine motor function through nearly exclusively contralateral projections from the cortex in primates. However, unilateral lesions to this system in various species are frequently followed by significant functional improvement, raising the possibility that bilateral projections of this pathway may exist or emerge after injury. To examine the detailed anatomy and projections of the corticospinal motor neurons in rhesus monkeys (n = 4), we injected the high-resolution anterograde tracer biotinylated dextran amine (BDA) into 126 sites centered about the right lower extremity (LE) primary motor cortex. Projection and termination patterns were quantified at lumbar levels L1, L4, and L7 and mapped by using serial-section reconstructions. Notably, a mean of 10.1 +/- 0.6% (+/- SEM) of corticospinal tract (CST) axons descended in the lateral CST ipsilateral to the cortical BDA injection, and 87.9 +/- 1.0% of total CST axons projected in the contralateral lateral CST. The ipsilateral ventral CST contained only 1.0 +/- 0% of all projecting CST axons, whereas the contralateral ventral CST contained 0.3 +/- 0.2% of all axons. In addition, a minor dorsal column CST projection was identified. Measurement of BDA-labeled terminals in the spinal cord gray matter revealed that 11.2 +/- 2.2% of CST axons terminated ipsilateral to the side of cortical injection, and the remainder terminated contralaterally. As previously reported, most CST axons terminated in spinal cord laminae V-VIII, as well as the laterodorsal motoneuronal group of lamina IX (which innervates distal extremity muscles). Notably, many CST axons crossed the spinal cord midline (mean 19.9 +/- 4.9 axons per 40-microm-thick section). Detailed single-axon reconstructions revealed that most ipsilaterally projecting lateral CST axons terminated in ipsilateral gray matter. Notably, we found that the bouton-like swellings of many ipsilateral CST axons descending in the dorsolateral tract were located within Rexed's lamina IX, in close proximity to motoneuronal somata. Thus, bilateral projections of corticospinal axons originating from a single motor cortex could contribute to bilateral control of spinal motor neurons and to the highly evolved degree of fine motor control in primates. Furthermore, bilateral CST projections from a single motor cortex could represent a potential source of plasticity after injury, as well as a target of therapeutic effort in neural regeneration strategies.

Animals↗
PubMed2006

Neonatal deafness results in degraded topographic specificity of auditory nerve projections to the cochlear nucleus in cats.

We previously examined the early postnatal maturation of the primary afferent auditory nerve projections from the cat cochlear spiral ganglion (SG) to the cochlear nucleus (CN). In normal kittens these projections exhibit clear cochleotopic organization before birth, but quantitative data showed that their topographic specificity is less precise in perinatal kittens than in adults. Normalized for CN size, projections to the anteroventral (AVCN), posteroventral (PVCN), and dorsal (DCN) subdivisions are all significantly broader in neonates than in adults. By 6-7 postnatal days, projections are proportionate to those of adults, suggesting that significant refinement occurs during the early postnatal period. The present study examined SG projections to the CN in adult cats deafened as neonates by ototoxic drug administration. The fundamental organization of the SG-to-CN projections into frequency band laminae is clearly evident despite severe auditory deprivation from birth. However, when normalized for the smaller CN size in deafened animals, projections are disproportionately broader than in controls; AVCN, PVCN, and DCN projections are 39, 26, and 48% broader, respectively, than predicted if they were precisely proportionate to projections in normal hearing animals. These findings suggest that normal auditory experience and neural activity are essential for the early postnatal development (or subsequent maintenance) of the topographic precision of SG-to-CN projections. After early deafness, the basic cochleotopic organization of the CN is established and maintained into adulthood, but the CN is severely reduced in size and the topographic specificity of primary afferent projections that underlies frequency resolution in the normal central auditory system is significantly degraded.

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