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Characterization of superior cervical ganglion neurons that project to the submandibular glands, the eyes, and the pineal gland in rats.

These studies sought to determine whether the cell bodies of rat superior cervical ganglion neurons projecting to three very different target organs differ in terms of their size, number, location within the ganglion and/or neuropeptide content, and whether these features are altered in response to neonatal deafferentiation of the ganglion. A series of retrograde tracer, immunocytochemical, and double-labeling studies revealed differences in the size, number, location and neuropeptide content of superior cervical ganglion neurons that project to the submandibular salivary glands, eyes, or pineal gland. The mean areas of the cell bodies of neurons projecting to the submandibular gland are largest, those projecting to the eye are smallest, and those projecting to the pineal are intermediate in size. Submandibular gland projecting neurons are found throughout the ganglion, while the eye and pineal projecting populations are localized to the rostral quadrants. The different subpopulations of target organ specific superior cervical ganglion neurons are heterogeneous in their content of vasoactive intestinal peptide-, neuropeptide Y- and somatostatin-like immunoreactivity. A greater percentage of submandibular gland than of pineal projecting neurons display vasoactive intestinal peptide-like immunoreactivity, but there are no differences in the percentage of neurons displaying neuropeptide Y- or somatostatin-like immunoreactivity between the target organ specific groups. Neonatal deafferentiation does not result in changes in the size, number or distribution of target organ specific neurons, or in the percentage of immunoreactive neurons in these populations. In conclusion, these studies provide evidence that the size and distribution of neurons and percentage of peptide-containing neurons in the superior cervical ganglion is related to the target organ innervated, but provides no evidence of exclusive target organ-peptide relationships.

Afferent Pathways↗

Dual projections of single cholinergic and aminergic brainstem neurons to the thalamus and basal forebrain in the rat.

Compelling evidence indicates that cholinergic basal forebrain neurons are strongly activated during waking, and concurrently thalamic spindle activity is suppressed and thalamocortical sensory transmission is facilitated. Both thalamus and basal forebrain are known to receive projections from brainstem cholinergic and aminergic neuronal pools that are involved in wake/sleep regulation. The present study addressed the question of whether single cholinergic and aminergic neurons contributed to both of these ascending projections, by using two fluorescent retrograde tracers combined with immunofluorescence. Cholinergic neurons projecting to both the basal forebrain and thalamus were found in the pedunculopontine and laterodorsal tegmental nuclei, representing an average of 8.0% of the total cholinergic cell population in these nuclei. Serotonergic neurons with dual projections were observed in the dorsal, median and caudal linear raphe nuclei, accounting for a mean of 4.7% of total serotonergic neurons in these nuclei. Relatively few noradrenergic neurons (2.0%) in the locus ceruleus projected to both target structures, and a very small subpopulation of histaminergic neurons (1.5%) in the tuberomammillary hypothalamic nucleus had dual projections. Of all brainstem neurons with dual projections, cholinergic and serotonergic neurons accounted for an overwhelming majority, with noradrenergic followed by histaminergic neurons representing the remaining minority. These data suggest that through dual projections, cholinergic and aminergic brainstem neurons can concurrently modulate the activity of neurons in the thalamus and basal forebrain during cortical arousal.

Acetylcholine↗

An electrophysiological study of the projections of motor neurones that mediate non-cholinergic excitation in the circular muscle of the guinea-pig small intestine.

The projections of neurones that produce the fast non-cholinergic excitatory junction potentials (e.j.p.s) in the circular muscle were analysed in the isolated ileum of the guinea-pig. Standard intracellular microelectrode techniques were used to record the amplitudes of such e.j.p.s in response to short trains of stimuli from transmural electrodes. Projections of the neurones around the circumference of the intestine were determined by plotting the change in e.j.p. amplitude with distance from longitudinally placed electrodes. Projections in the oral and anal directions were examined by recording at varying distances from transversely placed electrodes, and also by recording responses elicited close to longitudinal electrodes at various distances from lesions made 3-5 days earlier to interrupt orally and anally directed pathways. Experiments were performed in the presence of hexamethonium to determine the projections of the final motor neurones and in the absence of the drug to examine the projections of excitatory inputs to these neurones. With hexamethonium present, there was a decline in e.j.p. amplitude to 7.5% of maximum at 12 mm (a half circumference) from longitudinal stimulating electrodes. The decline was much less if hexamethonium was not present, and slightly greater if the myenteric plexus was removed. Thus, excitatory motor neurones and cholinergic neurones that impinge upon them both project circumferentially. When the longitudinal muscle and myenteric plexus were removed, and 3-5 days allowed for terminals to degenerate, no e.j.p.s could be recorded in the circular muscle, indicating that the fibres reach the circular muscle from the myenteric plexus. Following transverse lesions, substantial deficits in excitatory transmission only occurred within 1 mm oral or anal to the lesions indicating that the majority of neurones have only short projections along the intestine. A slight deficit in e.j.p. amplitude, up to 20%, was observed extending to about 5 mm oral; but normal transmission was restored by about 10 mm for the lesions. Thus there is a minority of excitatory motor neurones with oral projections up to about 10 mm in length. Results with transmural stimulation showed that these nerve fibres can cause excitation both when orthodromically and when antidromically stimulated, indicating that they provide collaterals along their lengths. With no hexamethonium present, e.j.p.s exhibited little decrement in amplitude over distances of over 30 mm oral or anal indicating that there are both ascending and descending cholinergic pathways that impinge on the final motor neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Topographic and zonal pattern of olivocerebellar projection to the paramedian lobule in the rabbit: an experimental study with an HRP retrograde tracing method.

Distribution of neurons in the inferior olive (IO) projecting to the paramedian lobule (PML) was studied in rabbits by means of retrograde transport of horseradish peroxidase (HRP). HRP was injected into various regions of different folia of the PML. Findings indicate zonal and to some extent topographic organization in olivocerebellar projections to PML folia. The neurons in corresponding areas of dorsal (dlPO) and ventral lamina (vlPO) of the principal olive (PO) project to composite zones D (D1 + D2) in sublobule f: medial, intermediate and lateral. In addition, the caudal part of the medial accessory olive (MAO) projects to the most laterally located zone (C2-lateral) and the caudal part of the dorsal accessory olive (DAO) to the most lateral zone (C3) in sublobule f. The middle part of the DAO sends projections to zone C1 located medially in sublobules d-a. The rostral and caudal parts of the DAO send projections to zone C3 in sublobules a and f, respectively. The rostral, middle and adjacent caudal parts of MAO, with no clear topographic organization, project to broad zone C2 in sublobules e-b. The neurons in restricted areas of the caudomedial part of the dlPO and vlPO, probably intermingled with those supplying the composite medial zone D in sublobule f, project to sublobules e-b to terminate in zones D1 and D2, respectively.

Animals↗

Participation effect from water projects on EPI.

It has been hypothesized that in addition to the direct health and amenity benefits of an improved water supply, there are other, more subtle, benefits to communities who participate in community-based water supply projects. A detailed empirical comparison of villages with and without community-based water projects in Indonesia and Togo suggests that such indirect benefits are substantial. Between 25 and 30% more children are immunized in villages with community-based water projects than in comparison villages which either have benefitted from non-participatory water projects, or have had no water project. From a comparison between the activities of villagers and workers in external agencies involved in water projects in the two countries, it is concluded that successful participatory water projects are best characterized as a partnership between the community and the external agency. Such projects require substantial inputs of time, resources, skill and persistence from both the community and the external agency. These inputs must be sustained by both parties in all phases--planning, construction and maintenance--if this partnership is to result in lasting improvements in water supply and other aspects of community life.

Child, Preschool↗

The differential ascending projections from the anterior, central and posterior regions of the lateral hypothalamic area: an autoradiographic study.

The ascending efferent projections of the neurons of the anterior (LHAa), central (LHAc) and posterior (LHAp) parts of the lateral hypothalamic area (LHA) have been studied using an autoradiographic analysis of the anterograde axonal transport after local injection of tritiated amino acids. Our results show that LHA regions have common projections particularly to the thalamus and to the hypothalamus. They also demonstrate the existence of differential projections: i.e. an anteroposterior gradient of projection sites according to anterior, central and posterior localisation of the LHA neurons. The LHAa neuronal projections terminate in the lateral septal area; the LHAc projections innervate the frontal cortex while LHAp neurons send their projections to the olfactory bulb and innervate both the cerebral cortex and the hippocampus. Only the LHAp neurons project measurably to the globus pallidus, the caudate putamen and the nucleus accumbens.

Animals↗

The developing chick isthmo-optic nucleus forms a transient efferent projection to the optic tectum.

The present work describes the formation of a transient efferent axonal projection from the isthmo-optic nucleus (ION) to the ipsilateral optic tectum of the chick embryo. Local application of either the carbocyanine dye DiI or rhodamine-B-isothiocyanate (RITC) to the superficial layers of the optic tectum resulted in retrograde labeling of the corresponding retinal region, and in anterograde staining of tectal axons projecting to the ION. In addition to these known projections, retrogradely labeled ION neurons appeared to be filled from the tectum. This projection, called the isthmo-tectal projection, could be characterized by means of various staining techniques: (i) It first appears at embryonic day E9 and gradually disappears after day E16. It is absent in the hatched chick. (ii) Both the cells inside the ION and those situated outside the border of the ION, the so-called ectopic cells, contribute to the formation of the isthmo-tectal projection. (iii) Double labeling from the contralateral retina (Fast blue) and from the ipsilateral tectum (DiI or RITC) revealed that some of the ION fibers projecting to the tectum are collaterals of axons normally directed to the retina. (iv) Microsurgical removal of the eye anlage early in development resulted in a numerical increase of the ION-tectal fibers. The results are discussed in terms of the role of transient projections during development.

Animals↗

The cerebellar projections to the superior colliculus and pretectum in the cat: an autoradiographic and horseradish peroxidase study.

Efferent projections from the cerebellar nuclei to the superior colliculus and the pretectum have been studied using both retrograde and orthograde labeling techniques in the cat. In order to identify what parts of the cerebellar nuclei project to the superior colliculus and the pretectum, the retrograde horseradish labeling technique was employed. In another set of experiments, tritiated amino acids were injected into each of the cerebellar regions from which the cerebello-tectal and cerebello-pretectal projections arise, and the laminar and spatial distributions of orthograde labeling in the superior colliculus and the pretectum were compared. The results showed that the cerebello-tectal projections arise from two different regions of the cerebellar nuclei: the caudal half of the medial nucleus and the ventrolateral part of the posterior interposed nucleus. Fibers arising from the medial nucleus distribute bilaterally in the superficial zone of the intermediate gray layer in the superior colliculus, while those originating from the posterior interposed nucleus terminate contralaterally in the deeper aspect of the intermediate gray layer and in the deep gray and white layers. Although the lateral nucleus does not contribute to the cerebello-tectal projection, it projects profusely to the pretectum contralaterally. The origin of the cerebello-pretectal projection lies in the parvicellular part of the lateral nucleus. Among several pretectal nuclei, the posterior pretectal, the medial pretectal nucleus and the reticular part of the anterior pretectal nucleus receive the cerebellar afferents. The findings of the differential projections from the cerebellum to the superior colliculus and the pretectum suggest that the cerebellum exerts a regulatory influence on visuo-motor and somato-motor transfer in these midbrain structures by differential circuits.

Animals↗

Visual experience and the maturation of the ipsilateral visuotectal projection in Xenopus laevis.

The effect of visual deprivation upon the maturation of the ipsilateral visuotectal projection has been studied in Xenopus laevis. This topographically ordered projection is polysynaptic. The first stage involves the retinal projection to the contralateral optic tectum. The tectum projects to the nucleus isthmi on the same side. The final stage is the crossed isthmotectal projection from the nucleus isthmi to the tectum ipsilateral to the eye. The topographic precision of connections at various points in this polysynaptic pathway has been investigated by quantifying single-unit and multi-unit receptive field sizes in the contralateral and ipsilateral visuotectal projections. Observations have been made on normal animals of different ages to plot the normal maturational course of events. The effects of visual deprivation on this maturational process has been studied. Between one week and one year after metamorphosis there is an increase in the precision of connections in both the contralateral and ipsilateral visuotectal projections. Visual deprivation had no effect upon the parameters of the contralateral visuotectal projection. Ipsilateral visuotectal single units in dark-reared animals had normal receptive field sizes. Ipsilateral multi-unit receptive fields in dark-reared animals were considerably larger than in normal animals. It was concluded that the effects of visual deprivation are limited to effects on the crossed isthmotectal component of the intertectal system. In this component, however, visual experience seems to play an important role in the normal development and modification of connections. It is suggested that visual experience is utilized to accommodate changes in the system required to respond to normal changes in interocular geometry that take place with development in Xenopus.

Animals↗

Projections of peptide-containing neurons in rat colon.

The distribution, origin and projections of nerve fibers containing vasoactive intestinal peptide, substance P, neuropeptide Y, galanin, gastrin-releasing peptide, calcitonin gene-related peptide, somatostatin or enkephalin were studied in the midcolon of the rat by immunocytochemistry and immunochemistry. Most of these nerve fibers had an intramural origin as was established by extrinsic denervation (serving of mesenterial nerves). Extrinsic denervation eliminated neuropeptide Y-containing fibers of presumably sympathetic origin together with sensory nerve fibers containing both substance P and calcitonin gene-related peptide. Co-existence of two peptides in the same neuron was studied by double immunostaining. This revealed co-existence of neuropeptide Y and vasoactive intestinal peptide in one population of intramural neurons; an additional population of intramural neurons was found to contain vasoactive intestinal peptide but not neuropeptide Y. All somatostatin-containing neurons in the submucous ganglia were found to harbor calcitonin gene-related peptide. A much larger population of submucous neurons containing calcitonin gene-related but not somatostatin was also detected. Some perivascular calcitonin gene-related peptide-containing nerve fibers (of intrinsic origin) harbored vasoactive intestinal peptide while others (of extrinsic origin) harbored substance P. The polarities and projections of the various peptide-containing intramural neurons in the transverse colon were studied by analysing the loss of nerve fibers upon local disruption of enteric nervous pathways (myectomy or intestinal clamping). Myenteric neurons containing vasoactive intestinal peptide, galanin, gastrin-releasing peptide, calcitonin gene-related peptide, somatostatin or vasoactive intestinal peptide/neuropeptide Y gave off 5-10-mm-long descending projections while those containing substance P or enkephalin issued approx. 5-mm-long ascending projections. Submucous neurons containing calcitonin gene-related peptide, somatostatin/calcitonin gene-related peptide or gastrin-releasing peptide issued both ascending (2-6 mm) and descending (2-6 mm) projections, those containing vasoactive intestinal peptide issued ascending (approx. 2 mm) projections, while those containing galanin or vasoactive intestinal peptide/neuropeptide Y lacked demonstrable oro-anal projections. Enkephalin-containing fibers could not be detected in the mucosa and the mucosal substance P-containing nerve fibers were too few to enable us to delineate their projections.

Animals↗

Evidence for co-existence of thyrotropin-releasing hormone, substance P and serotonin in ventral medullary neurons that project to the intermediolateral cell column in the rat.

The present study was conducted to determine if substance P-, thyrotropin-releasing hormone- and/or serotonin-immunoreactivities coexist in ventral medullary neurons that project to the intermediolateral cell column in the rat. Neurons that projected to the intermediolateral cell column were identified by the presence of retrogradely transported rhodamine bead-labeled microspheres in the cell body after an injection of the microspheres into the intermediolateral cell column of the third thoracic spinal cord segment. Co-existence was determined by using a combination of dual color immunohistochemistry and serial 4-microns sections that were immunostained with different antibodies. Antibodies to substance P, serotonin, and pre-pro-thyrotropin releasing hormone160-169 were used to identify substance P, serotonin and thyrotropin-releasing hormone, respectively. Neurons that contained substance P-, thyrotropin-releasing hormone- and/or serotonin-immunoreactivities and that projected to the intermediolateral cell column were present in the nucleus raphe magnus, the nucleus raphe pallidus, the nucleus reticularis magnocellularis pars alpha, the paragigantocellular reticular nucleus and the parapyramidal region. Neurons that projected to the intermediolateral cell column, in each of these regions, were found to contain each of the following combinations of immunoreactive neurochemicals: substance P and thyrotropin-releasing hormone: substance P and serotonin; thyrotropin-releasing hormone and serotonin; or substance P, thyrotropin-releasing hormone and serotonin. In addition, most of the regions also contained neurons that appeared to contain only one of the neurochemicals and that also projected to the intermediolateral cell column. The greatest number of neurons that projected to the intermediolateral cell column and that also contained two or more co-existing neurochemicals was present in the midline regions. This study demonstrates the presence of neurons in the ventral medulla that project to the intermediolateral cell column and contain three co-existing neurochemicals. This study also demonstrates the use of a new method for the localization of three neurochemicals in single projection-specific neurons.

Animals↗

The basal forebrain projection to the region of the nuclei gemini in the rat; a combined light and electron microscopic study employing horseradish peroxidase, fluorescent tracers and Phaseolus vulgaris-leucoagglutinin.

We have examined the location of basal forebrain cells projecting to the region of the nuclei gemini in the caudolateral hypothalamus of the rat using retrograde transport of wheatgerm agglutinin-horseradish peroxidase. Since many tracer-positive neurons were identified in ventral pallidal areas known to project to the mediodorsal nucleus of the thalamus, we also prepared several animals with wheatgerm agglutinin-horseradish peroxidase injections in mediodorsal thalamus. Many of the sections from both groups of animals were subsequently prepared for the demonstration of ventral pallidal regions, using either substance P or glutamate decarboxylase as a pallidal marker. Some animals received injections of different retrogradely transported fluorescent tracers in the mediodorsal thalamus and the nuclei gemini for the purpose of studying potential axon collateralization. The large gemini-projecting cells are diffusely scattered within the medial forebrain bundle area, from the caudal margin of the nucleus of the horizontal limb of the diagonal band to the rostral tip of the olfactory tubercle, and with a concentration of cells in the lateral part of the medial forebrain bundle region. Gemini-projecting cells were not found in the olfactory tubercle proper, including the islands of Calleja complexes, or in the ventral pallidal areas located dorsal to the medial forebrain bundle area underneath the lateral extension of the anterior commissure. Gemini-projecting cells within ventral pallidal areas were observed only in regions where the longitudinal fascicles of the medial forebrain bundle interdigitate with the rostroventral extension of the ventral pallidum. Anterogradely-labeled fiber plexuses in the region of the nuclei gemini were observed following injection of Phaseolus vulgaris-leucoagglutinin or Fluoro-Ruby into the forebrain regions containing retrogradely-labeled neurons following nuclei gemini injections of wheatgerm agglutinin-horseradish peroxidase. We found no evidence of cells with axonal projections to both mediodorsal thalamus and nuclei gemini. The gemini-projecting cells are generally large, triangular and plump, and the electron microscopic picture of gemini-projecting neurons is the same regardless of whether the cells are located in pallidal or non-pallidal areas.

Animals↗

Convergence of cortical and cerebellar projections on single basilar pontine neurons: a light and electron microscopic study in the rat.

A protocol that involved a combination of two orthogradely transported tracer substances, wheat agglutinin-horseradish peroxidase and Phaseolus vulgaris leucoagglutinin injected at separate locations in the same animal was utilized to investigate the possible congruence of axonal projection fields formed by the cerebral cortical and cerebellar afferents to the basilar pontine nuclei. When large placements of tracer material were made in the cerebellar nuclei to label the cerebellopontine projections and a second tracer was injected in one of several cerebral cortical areas to visualize certain corticopontine projections, it was noted that axon terminal zones of the cortical and cerebellar systems occupied greater or lesser amounts of the same basilar pontine territory depending on the location of the cerebral cortical injection. Cerebellopontine terminal fields exhibited their greatest congruency with projections from the motor cortex containing the representation for facial musculature and with projections from the forelimb sensorimotor cortex. A lesser degree of overlap was observed when cerebellar projection zones were visualized in combination with basilar pontine projections from sensory face cortex, hindlimb sensorimotor cortex, visual cortex and auditory cortex. In addition, it was apparent that portions of the cerebellopontine and corticopontine terminal fields did not overlap at all. A related series of electron microscopic experiments was undertaken to establish that within the zones of overlapping cerebellar and cortical projections, there was in fact a convergence of the two afferent systems on single basilar pontine neurons. Boutons of the corticopontine system were labeled by the orthograde transport of wheat germ agglutinin horseradish peroxidase injected into the sensorimotor cortex while cerebellopontine terminals were marked for electron microscopic identification in the same animal by transecting the brachium conjunctivum and allowing sufficient time for boutons in the pontine nuclei to exhibit degeneration. Although the number of definitive examples of convergence was small, nonetheless it was possible to observe single basilar pontine neuron dendrites receiving synaptic contacts from both the cortical and cerebellar afferents systems. Taken together these observations indicate that some basilar pontine neurons receive a dual or convergent input from the cerebral cortex and cerebellar nuclei. It is difficult to estimate the prevalence of such convergence since cortical and cerebellar inputs typically contact distal and proximal pontine neuron dendrites, respectively, thus limiting the chances that both types of boutons can be observed in contact with a single basilar pontine neuron dendrite.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Topographic distribution of the neurons of the central complex (centre médian-parafascicular complex) and of other thalamic neurons projecting to the striatum in macaques.

The distribution of the neurons of the central complex (or "centre médian-parafascicular complex") and of other thalamic regions projecting to the striatum was studied using a cartographic technique based on ventricular landmarks. The brain of a macaque was used as a reference for the cytoarchitectonic study of the complex. Three parts were isolated: the pars parafascicularis (or medial part), the pars media (or middle part) and the pars paralateralis (or lateral part). Wheat germ agglutinin conjugated to horseradish peroxidase was stereotaxically injected into either the sensorimotor or the associative territory of the striatum (i.e. the striatal space occupied by the axonal endings coming from either the sensorimotor or the associative cortex) of four macaques. Neurons projecting to the sensorimotor territory of the striatum were found to be located within the pars media (middle part) of the central complex while neurons projecting to the associative territory of the striatum were located within the pars parafascicularis. In all experimental cases, labelled neurons were scarce or absent in the pars paralateralis (or lateral part). Outside the central complex, neurons projecting to the sensorimotor territory of the striatum were scattered within the lateral part of the lateral mass, in the intralaminar nuclei and in the posterior part of the internal lamina. Neurons projecting to the associative territory of the striatum were observed mainly in the paraventricular region, dorsal to the rostral part of the lateral mass, and in the dorsolateral part of the nucleus oralis medialis. Our three-dimensional analysis of the clusters of the central complex cells projecting to the two striatal territories justifies the partitioning of the central complex into three parts. The pars media (or middle part), which projects to the sensorimotor territory of the striatum, receives selectively pallidal afferent axons. It belongs to the Nauta-Mehler loop, a closed loop linking the central complex to the basal ganglia. The pars parafascicularis, which projects to the associative territory of the striatum, seems more related to oculomotor neuronal systems. The pars paralateralis (or lateral part) appears to have very little, if any, relation with the striatum.

Afferent Pathways↗

Spinal distribution and collateral projections of rat spinomesencephalic tract cells.

The distribution of cells belonging to the rat spinomesencephalic tract was studied by means of the retrograde transport of fluorescent dyes. Bilateral midbrain injections of cytoplasmic and nuclear tracers were made in order to evaluate the location of ipsilateral, contralateral, or bilaterally projecting cells. Spinal neurons with ascending projections to midbrain and descending propriospinal projections were identified by midbrain and spinal injections of different cytoplasmic labels. The locations of spinomesencephalic tract cells included seven regions of the spinal gray matter: marginal zone, lateral neck of the dorsal horn, nucleus proprius, the region around the central canal, the lateral cervical and spinal nuclei and the ventral horn. Cells projecting to the ipsilateral or contralateral midbrain had similar distributions and were frequently found in clusters with overlapping dendritic fields. Approximately 75% of spinomesencephalic cells projected to the contralateral midbrain. The largest contribution to the spinomesencephalic tract cell population was found in cervical cord segments 1-4. Cells with bilateral projections accounted for nearly 2% of all labeled cells, whereas 5% had both ascending and descending projections. Spinomesencephalic cells were found to have varying dendritic fields and morphology, e.g. fusiform, pyramidal, round/oval, and multipolar. The results of the present study lend further support to the view that the spinomesencephalic tract is a multi-component pathway with varied origins and projection targets.

Afferent Pathways↗

The organization of midbrain projections to the striatum in the primate: sensorimotor-related striatum versus ventral striatum.

In order to examine the organization of nigrostriatal projections in the primate, the retrograde tracers Lucifer Yellow conjugated to dextran amines and horseradish peroxidase conjugated to wheatgerm agglutinin were injected into different regions of the dorsolateral and ventral striatum. Based on the topography of cortical inputs to the striatum, the dorsolateral striatum is associated with the motor system, and the ventral striatum is related to the limbic system. Our results indicate that although midbrain neurons projecting to the ventral and dorsolateral striatum are mostly separate, there are neurons projecting to these different striatal territories that overlap in the medial substantia nigra. The dopaminergic neurons of the ventral mesencephalon can be subdivided into dorsal and ventral tiers that include the cells of the ventral tegmental area, the substantia nigra pars compacta, and the retrorubral area. Neurons projecting to the ventral striatum are found in both the dorsal and ventral tiers. A large number of neurons occupying the medial densocellular zone of the ventral tier are labeled following injections into different regions of the ventral striatum. Neurons projecting to the sensorimotor-related striatum are derived almost exclusively from the ventral tier. Many of these neurons are located very ventrally in the substantia nigra, where clusters of neurons invade the pars reticulata. In addition, labeled neurons are found throughout the mediolateral extent of the densocellular zone of the pars compacta. Notably, neurons are labeled in the medial densocellular zone following injections into the dorsolateral and ventral striatum. Mesencephalic neurons projecting to different striatal territories are distinct in that dorsal tier neurons mainly innervate the ventral striatum, whereas the ventral columns of neurons in the ventral tier innervate the sensorimotor-related striatum. Thus, the dopaminergic regulation of the sensorimotor-related striatum and the ventral striatum may be different. However, a subgroup of dopaminergic neurons in the medial densocellular zone projects to both striatal territories. Such divergent projections may allow the substantia nigra to serve as a link, connecting different striatal territories, via their connections with the substantia nigra.

Animals↗

The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat.

The organization of projection neurons in the ventral tegmental area (VTA), and in adjacent parts of the raphe nuclei medial to it (the central and rostral linear, and interfascicular nuclei), the mammillary body (the supramammillary region and the tuberomammillary nucleus), and the substantia nigra have been examined in the rat with Kuypers' retrograde double labeling method, and with a combined retrograde labeling (with true blue)-immunohistochemical method for the demonstration of dopaminergic neurons. First, the distribution, within the VTA and adjacent regions, of dopaminergic and non-dopaminergic cells that project to terminal fields in the telencephalon (nucleus accumbens, lateral septum, pre- and supragenual fields of the anterior limbic cortex, amygdala, dorsal hippocampus, and entorhinal area), in the diencephalon (lateral habenula), and in the brainstem (locus coeruleus, and parabrachial nucleus) was determined. Then, 15 different combinations of injections of the tracers bisbenzimide and true blue into different terminal fields were made to determine whether individual cells in the region of the VTA send collaterals to more than one site. Taken together, the results indicate that essentially separate groups of cells in the VTA and adjacent regions of the raphe project to each terminal field. In addition, each group can be further divided into dopaminergic and non-dopaminergic components, although the proportion of dopaminergic cells in each group can vary from over 80% (e.g., to the nucleus accumbens) to less than 1% (to the lateral habenula and to the locus coeruleus). In addition, it was found that the supramammillary region, which contains a dense extension of the A10 cell group in its medial part, and the tuberomammillary nucleus, project to, or through, most of the regions injected with retrograde tracers. Virtually all of the projections from the VTA and adjacent regions are partially crossed, the percentage of cells on the uninjected side ranging from over 40% (e.g., for locus coeruleus injections) to only about 2% (e.g., for amygdalar injections). Most of the groups of projection neurons in the region of the VTA are considerably intermixed with the exception of those that project to the lateral septum, to the lateral habenula, and to the hippocampal formation, which are concentrated in ventral and medial parts of the VTA, and in the raphe nuclei medial to the VTA. It was concluded that in the ventral part of the midbrain, essentially separate groups of aminergic and non-aminergic neurons in both the reticular formation (VTA) and in the adjacent nuclei of the raphe project bilaterally to a variety of similar terminal fields in the telencephalon, diencephalon, and brainstem. Further work at the single cell level is needed to determine whether these cell groups are differentially innervated by known inputs to the VTA and adjacent regions, most of which appear to descend through the medial forebrain bundle from sites in the limbic system and hypothalamus.

Animals↗

Rat central amygdaloid nucleus projections to the bed nucleus of the stria terminalis.

The projections from the central amygdaloid nucleus (Ce) to different subdivisions of the bed nucleus of the stria terminalis (BNST) were investigated using retrograde transport of fluorescent dyes. Iontophoretic injections of either Fast Blue (FB) or bisbenzimide (BB) were applied to the anterior medial, posterior medial, anterior lateral and posterior lateral parts of the bed nucleus of the stria terminalis. The anterior medial BNST receives projections from caudal part of medial Ce (CeM). The posterior medial BNST receives projections specifically from the intermediate subdivision of Ce, though in some cases projections from the ventral subdivision (CeV) of Ce were seen. The anterior lateral BNST receives projections primarily from the caudal lateral Ce (CeL) as well as middle and caudal part of CeM. The posterior lateral BNST receives projection from rostral CeL as well as the CeV and lateral capsular Ce. In general, the results indicate that the major subdivisions of the BNST receive projections from Ce subdivisions having similar connections with diencephalic or brainstem cell groups. Additional evidence is presented suggesting that Ce-BNST projections are part of an extensive system of intrinsic connections linking similar groups of neurons in both the Ce and BNST as well as within Ce.

Amidines↗