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PubMed1994

NADPH diaphorase (nitric oxide synthase)-containing nerves in the enteropancreatic innervation: sources, co-stored neuropeptides, and pancreatic function.

Pancreatic ganglia are innervated by neurons in the gut and are formed by precursor cells that migrate into the pancreas from the bowel. The innervation of the pancreas, therefore, may be considered an extension of the enteric nervous system. NADPH-diaphorase is present in a subset of enteric neurons. We investigated the presence of NADPH-diaphorase in the enteropancreatic innervation, the contribution of extrinsic nerves to the NADPH-diaphorase-containing fibers of the gut and pancreas, and the coincident expression of NADPH-diaphorase NADPH-diaphorase in intrinsic neurons of these organs with neuropeptides. The possible role of nitric oxide in the neural regulation of pancreatic secretion was studied in isolated pancreatic lobules. Neuronal perikarya with NADPH-diaphorase activity were found in both Dogiel type I and type II neurons of the myenteric plexus of the stomach and duodenum. All galanin (GAL)-immunoreactive neurons and a small subset of vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-immunoreactive neurons contained NADPH-diaphorase activity. NADPH-diaphorase activity was also found in a subset of VIP and NPY-immunoreactive pancreatic neurons. Retrograde tracing with FluoroGold established that NADPH-diaphorase-containing neurons in the bowel project to the pancreas. NADPH-diaphorase-containing fibers were also found to be provided to both organs by neurons in dorsal root ganglia. Secretion of amylase was evoked by L-arginine. This effect was prevented by N(G)-nitro-L-arginine (L-NNA), which also inhibited VIP-stimulated secretion of amylase; however, L-NNA had no effect on amylase secretion stimulated by carbachol. These results provide support for the hypothesis that nitric oxide plays a role in the neural regulation of pancreatic secretion.

Amylases↗
PubMed1994

Persistence of rubrospinal projections following spinal cord injury in the rat.

Recent neurophysiological and magnetic resonance imaging studies of clinically "complete" human spinal cord injuries indicate that some patients have considerable subclinical function and substantial morphological integrity of descending spinal tracts. In contrast, extensive histopathological changes, including cell death, have been described in central nervous system nuclei projecting to the cord following experimental transection or hemisection of the spinal cord in animal models. We have used a rodent model of severe compression cord injury that more closely resembles the clinical pathophysiology to investigate the extent of the persistence of the rubrospinal projection. Counts of red nucleus neurons retrogradely labelled with Fluorogold demonstrate that in contrast to the results obtained with transection models, compression injuries of the spinal cord do not result in massive loss of rubrospinal projections, at least up to 8 weeks postinjury. The results also suggest that many of the axons persist distal to the lesion site and that they are functionally intact with respect to retrograde transport capabilities.

Animals↗
PubMed1994

Direct projections from the entopeduncular nucleus to the lower brainstem in the rat.

The present study reports the existence of projection fibers from the entopeduncular nucleus to the superior colliculus and lateral parts of the pontobulbar tegmental regions (so-called lateral tegmental field) in the rat, suggesting that the entopeduncular nucleus may control eye-head and orofacial movements via these projection fibers. The anterograde axonal tracing with Phaseolus vulgaris-leucoagglutinin has revealed that the entopedunculotectal fibers terminate, bilaterally, with an ipsilateral predominance, in the deep layers of the superior colliculus through its rostral one-third level and that the entopedunculotegmental fibers terminate, bilaterally, with an ipsilateral predominance, in the parabrachial area, reticular formation surrounding the trigeminal motor nucleus, and parvicellular, dorsal, and ventral reticular nuclei. The cells of origin of the entopedunculotectal and entopedunculotegmental projections have been identified by retrograde axonal tracing with Fluoro-Gold and cholera toxin B subunit. The entopedunculotectal or entopedunculotegmental fibers originate, respectively, from the dorsal or ventral part of the entopeduncular nucleus. Additionally, a series of fluorescent retrograde double-labeling experiments with Fast Blue and Diamidino Yellow have indicated that single entopeduncular nucleus neurons projecting to the superior colliculus or lateral tegmental field often send their axon collaterals to the lateral habenular nucleus. The entopedunculotectal fibers are assumed to control head movements, which may be provoked via the tectospinal fibers, and further to participate in eye movements as the nigrotectal fibers that have been known to arise from the substantia nigra pars reticulata to end in the deep layers of the superior colliculus primarily through its caudal two-thirds level. The entopedunculotegmental fibers are presumed to be involved in control of orofacial movements, because the sites of termination of the entopedunculotegmental fibers correspond well with the reported areas of distribution of premotor interneurons for the trigeminal motor, facial, and hypoglossal nuclei.

Amidines↗
PubMed1994

Pedunculopontine nucleus in the squirrel monkey: cholinergic and glutamatergic projections to the substantia nigra.

The distribution and chemospecificity of the pedunculonigral neurons have been studied in squirrel monkeys (Saimiri sciureus) with cholera toxin subunit B (CTb) and fluorogold (FG) as retrograde tracers combined with immunohistochemistry for choline acetyltransferase (ChAT), glutamate, and the calcium binding protein calbindin D-28k. The injection of either CTb or FG into the substantia nigra produces prominent retrograde cell labeling in the mesopontine tegmentum. Labeled neurons are particularly numerous at the level of the decussation of the superior cerebellar peduncle, where they abound principally in the pars dissipata of the pedunculopontine nucleus (PPN). A significant proportion of retrogradely labeled neurons in the PPN display ChAT immunoreactivity. Within the entire PPN, approximately 25% of the retrogradely labeled neurons express ChAT immunoreactivity, but proportions of doubly labeled neurons are about 35%, 25%, and 15% in the rostral, middle, and caudal thirds of the PPN, respectively. These doubly labeled neurons are scattered among numerous retrogradely labeled neurons that are ChAT-negative and whose number increases along the rostrocaudal extent of the PPN. Several retrogradely labeled neurons in the PPN display glutamate immunoreactivity, but very few express calbindin. This study provides the first direct evidence for the involvement of cholinergic and glutamatergic neurons in the pedunculonigral projection in primates. Furthermore, the fact that some neurons of the PPN display both ChAT and glutamate immunoreactivity indicates that single neurons in the mesopontine tegmentum may exert a two-fold effect upon dopaminergic neurons of the substantia nigra. This dual cholinergic and glutamatergic pedunculonigral projection may play a crucial role in the functional organization of primate basal ganglia.

Animals↗
PubMed1994

Intergeniculate leaflet: an anatomically and functionally distinct subdivision of the lateral geniculate complex.

The intergeniculate leaflet (IGL) in the rat is a distinctive subdivision of the lateral geniculate complex that participates in the regulation of circadian function through its projections to the circadian pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus. The present investigation was undertaken to provide a precise definition of the IGL and a characterization of its neuronal organization including neuronal morphology, chemical phenotype, connections, and synaptic organization. The IGL extends the entire rostrocaudal length of the geniculate complex and contains a distinct population of small to medium neurons. In Golgi preparations, the neurons are multipolar with dendrites largely confined to the IGL. The neurons can be subdivided into three groups on the basis of neurotransmitter content and projections: (1) neurons that contain GABA and neuropeptide Y and project to the SCN; (2) neurons that contain GABA and enkephalin and project to the contralateral IGL; and (3) a small group of neurons that projects to the SCN but not characterized as yet by neurotransmitter content. The IGL receives dense, bilateral input from retinal ganglion cells and dense substance P input of unknown origin. A number of neurons in the anterior hypothalamic area and, particularly, the retrochiasmatic area project to the IGL, and there are sparse projections from brainstem monoamine and cholinergic neurons. The synaptic organization of the IGL is complex with afferents terminating in glomerular complexes that include axoaxonic synaptic interactions. Virtually all IGL afferents synapse upon dendrites and spines, with the densest synaptic input occurring on the distal portions of the dendritic arbor. The organization of the IGL and its connections as revealed in this analysis is in accord with its role in the integration of visual input with other information to provide feedback regulation of the SCN pacemaker.

Animals↗
PubMed1994

A topographically organized gamma-aminobutyric acid projection from the ventral pallidum to the nucleus accumbens in the rat.

Anatomical and electrophysiological studies have indicated that a reciprocal projection from the ventral pallidum back to the nucleus accumbens exists and has functional relevance. In this study, the topographical projection from the ventral pallidum to the nucleus accumbens was examined by using retrograde tracing with fluoro-gold iontophoresed in subcompartments of the nucleus accumbens in rats combined with either in situ hybridization for glutamic acid decarboxylase and preproenkephalin mRNA or substance P immunoreactivity. Deposits made into the medial nucleus accumbens preferentially labeled neurons in the medial ventral pallidum, while deposits into the dorsolateral nucleus accumbens, at or lateral to the anterior commissure, labeled primarily cells in the dorsal and lateral ventral pallidum. A mediolateral to rostrocaudal topography was also observed, with the medial deposits preferentially labeling cells in rostral ventral pallidum and the lateral deposits resulting in retrogradely labeled cells in the ventral pallidum below the crossing of the posterior anterior commissure (subcommissural) as well as below the globus pallidus (sublenticular). The majority of cells retrogradely labeled with fluoro-gold were double-labeled for glutamic acid decarboxylase mRNA. In contrast, very few retrogradely labeled neurons in the ventral pallidum were double labeled for mRNA for preproenkephalin. These data demonstrate a topographically organized projection from the ventral pallidum to the nucleus accumbens that is primarily gamma-aminobutyric acid (GABA)-ergic and reciprocal to the GABAergic projection from the nucleus accumbens to the ventral pallidum.

Animals↗
PubMed1994

Relationship of thalamic basal forebrain projection neurons to the peptidergic innervation of the midline thalamus.

To better understand the input-output organization of the midline thalamus, we compared the distribution of its peptidergic and monoaminergic afferents, which were visualized by using immunocytochemistry, with the distribution of neurons projecting to different basal forebrain structures, which were mapped using retrograde fluorescent tracers. Serotonin and most of the peptides were found throughout paraventricular thalamic nucleus (PV) and in other midline and intralaminar nuclei (type 1 pattern). Neuropeptide Y, alpha MSH and the catecholamine synthetic enzymes were largely restricted to dorsolateral PV (type 2 pattern). Vasopressin was found in dorsomedial PV and intermediodorsal nucleus in a pattern complementary to the type 2 distribution (type 3 pattern). Neurons projecting to accumbens core were present in paraventricular, intermediodorsal, and other midline nuclei. Neurons projecting to accumbens shell and to central amygdaloid nucleus were found in dorsal PV. The peptidergic zones were only loosely correlated with the distribution of different classes of projection neurons. The type 2 pattern overlapped best with neurons projecting to accumbens shell, and to a lesser extent to central amygdaloid nucleus, while the type 3 pattern overlapped best with neurons projecting to core of accumbens. This partial overlap suggests that some brainstem and hypothalamic nuclei preferentially affect different basal forebrain targets through the midline thalamus, and may allow, for example, information about stress to specifically influence accumbens shell and central amygdaloid nucleus. Nevertheless, most of the peptidergic afferents (type 1 pattern) to midline thalamus cover neurons projecting throughout the basal forebrain, which suggests that all of these neurons receive a variety of brainstem and hypothalamic inputs.

Afferent Pathways↗
PubMed1994

Fine structure of rat septohippocampal neurons. III. Recovery of choline acetyltransferase immunoreactivity after fimbria-fornix transection.

Most cholinergic projection neurons in the medial septal nucleus (MS) lose their capability to synthesize choline acetyltransferase (ChAT) after axotomy by bilateral fimbria-fornix transection. We have recently shown that identified septohippocampal neurons survive axotomy up to 10 weeks and display fine-structural characteristics of cells in control rats. However, the fate and functional role of these neurons remained unclear. Here we describe observations made in rats which survived axotomy for 6 months. Adult Sprague-Dawley rats were subjected to bilateral transection of the fimbria-fornix system. In some animals septohippocampal projection neurons were labeled by the retrograde fluorescent tracer Fluoro-Gold (FG) prior to axotomy. After varying survival times following fimbria-fornix transection, the animals were fixed and sections of the septal region immunostained for ChAT. Three weeks postlesion, the number of ChAT-positive cells in the MS was reduced to 19% of control, suggesting a severe neuronal loss. However, 10 weeks and 6 months after axotomy this value increased to 28% and 54%, respectively. Fine-structural analysis of ChAT-positive neurons after 6 months survival revealed all characteristics of vital cells including normal input synapses. The majority of these cells could be identified as former septohippocampal projection neurons by the presence of FG. We conclude that many neurons in the MS have the capacity to restore their transmitter synthesis in a long-lasting process following axotomy.

Animals↗
PubMed1994

Serotoninergic and nonserotoninergic neurons in the medullary raphe system have axon collateral projections to autonomic and somatic cell groups in the medulla and spinal cord.

Fluorescent double retrograde-tracing studies combined with fluorescent immunostaining for serotonin were carried out to determine the potential patterns of divergence in axonal projections to autonomic and somatic motor sites from medullary raphe and parapyramidal neurons. Injections (20-60 nl) of combinations of fluorescent retrograde tracers (Fast Blue, fluoro-gold, green latex microspheres, Diamidino Yellow) were made into the intermediolateral cell column (IML) of the spinal cord and the brainstem lateral tegmental field or ventral horn of the lumbar spinal cord of male Wistar rats. The animals were perfused after a 7-10-day survival period, and the brains were removed, sectioned (50 microns), and immunostained for serotonin. Following injections of different retrograde-tracer substances into the IML of the thoracic cord and the ventral horn of the lumbar cord, 36% of the neurons with axon collateral projections to the IML and the lumbar ventral horn were serotoninergic. Following injections of different retrograde-tracer substances into the IML and the lateral tegmental field, 26% of the neurons with axon collateral projections to the IML and the lateral tegmental field were serotoninergic. Many of the medullary neurons with projections to the lateral tegmental field and the lumbar cord were located dorsal and lateral to those neurons with projections to the IML. The results indicate that serotoninergic and nonserotoninergic neurons of the midline raphe system and parapyramidal region have axon collateral branches to the IML and the lateral tegmental field or the IML and the lumbar ventral horn. These projection neurons may form the anatomical substrate for the integration of autonomic and somatic motor activity.

Amidines↗
PubMed1995

Enhanced but delayed axonal sprouting of the commissural/associational pathway following a combined entorhinal cortex/fimbria fornix lesion.

From previous lesion studies of the hippocampus it has been reported that axons of the commissural/associational pathway expand their termination zone in the molecular layer of the dentate gyrus by 20-25% in response to loss of input from the entorhinal cortex. However, although much is known about the response of the commissural/associational pathway with regard to extent, latency, and speed of the reinnervation response following an entorhinal cortex lesion, little is known about how the loss of additional afferent systems might modulate this response. To address this issue, we examined at 14, 30, and 45 days postlesion, the sprouting of commissural/associational afferents following either a unilateral fimbria fornix transection, a unilateral entorhinal cortex lesion, or combined lesions of both the entorhinal cortex and the fimbria fornix. Loss of septal innervation to the hippocampus was assessed using the cholinesterase stain, whereas sprouting from the commissural/associational pathway was determined from Holmes fiber-stained sections. In addition, the Timms stain was used to examine the time course of the loss of terminal fields of the various zinc-containing afferent systems within the hippocampus. Following the removal of input to the hippocampus via the fimbria fornix transection, there was no evidence of sprouting of the commissural/associational fibers into the deafferented portion of the dentate gyrus. In contrast, rats receiving an entorhinal cortex lesion showed a significant increase (28%) in the width of the commissural/associational fiber plexus that was present by 14 days postlesion. By comparison, the magnitude of the expansion of the commissural/associational fiber plexus was significantly larger after lesioning both the entorhinal cortex and the fimbria than after the entorhinal cortex lesion alone (45% vs. 28%). In addition, the expansion of the commissural/associational fiber plexus was not increased at 14 days postlesion but was significantly increased at 30 days postlesion. The delay in the sprouting of the commissural/associational pathway coincided with the time course of loss of zinc-containing fibers in the outer molecular layer of the dentate gyrus as assessed with the Timms stain. These results suggest that the magnitude and time course for the sprouting of axons from the commissural/associational pathway into the partially deafferented hippocampus of the adult rat is lesion dependent and that the effect of the loss of input from the entorhinal cortex can be modulated and enhanced by the concomitant depletion of input from the fimbria fornix.

Animals↗
PubMed1995

The retinohypothalamic tract originates from a distinct subset of retinal ganglion cells.

The retinal ganglion cells giving rise to retinohypothalamic projections in the rat were identified using retrograde transport of horseradish peroxidase (HRP) or FluoroGold injected into the suprachiasmatic nucleus (SCN), and using transneuronal transport of the Bartha strain of the swine herpesvirus (PRV-Bartha). When PRV-Bartha is injected into one eye, it is taken up by retinal ganglion cells, replicated, transported to axon terminals in the SCN, and released. There the virus may take one, or both, of two paths to retinal ganglion cells in the contralateral eye: 1) uptake by SCN neurons, replication, and release from the neurons with uptake and retrograde transport in retinal afferents originating in the contralateral retina; 2) transneuronal passage through axo-axonic appositions between retinal afferents in the SCN with subsequent retrograde transport of virus to the contralateral retina. The ganglion cells thus labeled are a homogeneous population of small neurons (mean diameter, 12.8 +/- 2.2 microns and mean area, 81.8 +/- 21.8 microns 2) with sparsely branching dendrites that are widely distributed over the retina. This population is best identified when virus labeling of retinal projections in areas beyond the hypothalamus is eliminated by lateral geniculate lesions that transect the optic tract at its entry into the geniculate complex. The same population is labeled with retrograde tracers but, with both HRP and FluoroGold, other ganglion cells are labeled, presumably from uptake by fibers of passage, indicating that the virus is a more reliable marker for ganglion cells giving rise to retinohypothalamic projections. The ganglion cells identified correspond to a subset of type III, or W, cells.

Animals↗
PubMed1995

Premotor neurons for trigeminal motor nucleus neurons innervating the jaw-closing and jaw-opening muscles: differential distribution in the lower brainstem of the rat.

The distribution of premotor neurons for trigeminal motor nucleus neurons innervating the jaw-closing and jaw-opening muscles was examined in the lower brainstem of the rat by using retrograde and anterograde labeling techniques. First, Fluorogold, a fluorescent retrograde tracer, was injected into the dorsolateral or ventromedial division of the trigeminal motor nucleus, each of which contains motoneurons innervating the jaw-closing or jaw-opening muscles, respectively. Second, Phaseolus vulgaris-leucoagglutinin, an anterograde tracer, was injected into each of the lower brainstem sites, where clusters of retrogradely labeled premotor neurons had been seen in the first set of experiments. Third, after injection of the anterograde tracer into a lower brainstem site, followed by injection of the retrograde tracer cholera toxin B subunit into a masticatory muscle, termination of anterogradely labeled axons onto retrogradely labeled motoneurons was confirmed with the aid of a confocal laser-scanning microscope. It was found that the premotor neurons distributed in the mesencephalic trigeminal nucleus, medial part of the parabrachial region, supratrigeminal region, and dorsal parts of the principal sensory, oral spinal and interpolar spinal trigeminal nuclei project preferentially to the dorsolateral division of the trigeminal motor nucleus, whereas those in the lateral part of the parabrachial region, intermediate parts of the principal sensory, oral spinal and interpolar spinal trigeminal nuclei, and alpha part of the gigantocellular reticular nucleus project preferentially to the ventromedial division of the trigeminal motor nucleus. The dorsal and lateral parts of the medullary reticular formation and the medullary raphe nuclei contain premotor neurons of both types. Group k motoneurons, a cluster of trigeminal motoneurons that innervate the tensor tympani muscle, receive projection fibers predominantly from the dorsolateral part of the oral pontine reticular formation.

Animals↗
PubMed1995

Arcuate nucleus neurons that project to the hypothalamic paraventricular nucleus: neuropeptidergic identity and consequences of adrenalectomy on mRNA levels in the rat.

The possible role that the hypothalamic arcuate nucleus might play in mediating the increase in paraventricular nucleus corticotropin-releasing hormone mRNA levels following adrenalectomy was investigated in two series of experiments. In the first series in situ hybridization histochemistry was used to quantify levels of eight accurate nucleus neuropeptide and neurotransmitter mRNAs in neurons that potentially relay adrenal steroid feedback to the paraventricular nucleus. In the second series of experiments, arcuate neuropeptidergic projections to the hypothalamic paraventricular nucleus were characterized using retrograde tracing in combination with in situ hybridization histochemistry. Despite an increase in paraventricular nucleus corticotropin-releasing hormone (60%) and pituitary proopiomelanocortin mRNA levels (sixfold), arcuate mRNA levels for proopiomelanocortin, neuropeptide Y, somatostatin, galanin, dynorphin, tyrosine hydroxylase, glutamate decarboxylase, and the glucocorticoid receptor were unchanged 14 days following adrenalectomy. Neuropeptidergic characterization of arcuatoparaventricular projections was achieved by injection of the retrograde tracer fluorogold into the paraventricular nucleus; retrogradely labeled neurons were characterized with polyclonal antisera against fluorogold in combination with oligonucleotide probes directed against neuropeptide Y, proopiomelanocortin, or somatostatin. Out of these three arcuate neuropeptide Y mRNA was contained in 18% of the fluorogold-positive neurons in the arcuate, proopiomelanocortin mRNA was contained in 8%, and somatostatin mRNA was contained in 6%. Overall, the results from both experiments suggest that the arcuatoparaventricular neuropeptide Y, proopiomelanocortin, and somatostatin projections are not sensitive to a chronic (14 day) lack of adrenal steroids. These projections as well as the other arcuate neurotransmitter and neuropeptide systems appear not to contribute to the persistent elevations in paraventricular nucleus corticotropin-releasing hormone mRNA levels or pituitary proopiomelanocortin mRNA levels found in 14 day adrenalectomized rats.

Adrenal Glands↗
PubMed1995

Efferent projections of the paraventricular thalamic nucleus in the rat.

The paraventricular nucleus of the thalamus (PVT) receives input from all major components of the circadian timing system, including the suprachiasmatic nucleus (SCN), the intergeniculate leaflet and the retina. For a better understanding of the role of this nucleus in circadian timing, we examined the distribution of its efferent projections using the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). The efferent projections of the PVT are loosely organized along its dorsal-ventral and anterior-posterior axes. The anterior PVT sends projections to the SCN; the dorsomedial and ventromedial hypothalamic nuclei; the lateral septum; the bed nucleus of the stria terminalis; the central and basomedial amygdaloid nuclei; the anterior olfactory nucleus; the olfactory tubercle; the nucleus accumbens; the infralimbic, piriform, and perirhinal cortices; the ventral subiculum; and the endopiriform nucleus. A small PHA-L injection, restricted to the ventral portion of the anterior PVT, produces a similar pattern of labeling, except for a marked decrease in the number of labeled fibers in the hypothalamus, cortex, and lateral septum and an increase in labeling in the endopiriform nucleus and basolateral amygdaloid nucleus. The posterior PVT has a more limited efferent distribution than the anterior PVT, terminating in the anterior olfactory nucleus; the olfactory tubercle; the nucleus accumbens; and the central, basolateral, and basomedial nuclei of the amygdala. Our results show that the anterior PVT is ideally situated to relay circadian timing information from the SCN to brain areas involved in visceral and motivational aspects of behavior and to provide feedback regulation of the SCN.

Amygdala↗
PubMed1995

Nerve growth factor prevents apoptotic cell death in injured central cholinergic neurons.

Experimental lesions have been widely used to induce neuronal degeneration and to test the ability to trophic molecules to prevent lesion-induced alterations, but these studies have not demonstrated unequivocally that afflicted neurons die as a result of these manipulations. The documentation of neuronal death in the above-described models and the time when it occurs after injury are crucial for the interpretation of trophic effects. In the present study, we combined multiple approaches to investigate the nature of retrograde neuronal changes in cholinergic neurons of the medial septal nucleus (MSN) after complete, unilateral transection of the fimbria-fornix (F-F). Projections neurons of the MSN were prelabeled with the fluorescent tracer Fluoro-gold (FG) 1 week prior to lesion. By counting both FG-labeled and choline acetyltransferase (ChAT)-immunoreactive neurons in the MSN at multiple time points postaxotomy, we differentiated the phenotypic response to injury from the degenerative process and established a critical time between the third and fourth weeks postaxotomy, during which approximately 50% of fluorescent perikarya disappear. Working in the previous time window, we identified dying cells by electron microscopy (EM) and terminal transferase-mediated (TdT) deoxyuridine triphosphate (d-UTP)-biotin nick end labeling (TUNEL) and showed that MSN neurons die via apoptosis, beginning at 16 days postaxotomy. An additional group of animals was allowed to survive for 1 month (i.e., 10 days after cell death has been completed); during this period, animals were treated with intraventricular nerve growth factor (NGF). Quantitative analysis of surviving cholinergic perikarya showed that NGF prevented degeneration of the majority of neurons. In concert, the results of the present study establish that NGF does not merely protect the phenotype but also prevents cell death in lesioned central cholinergic neurons.

Acetylcholine↗
PubMed1995

Fate of GABAergic septohippocampal neurons after fimbria-fornix transection as revealed by in situ hybridization for glutamate decarboxylase mRNA and parvalbumin immunocytochemistry.

Many septohippocampal neurons are GABAergic and are affected by transection of the fimbria-fornix, like the septohippocampal cholinergic cells. Here we have studied the changes that occur in GABAergic septohippocampal neurons following fimbria-fornix transection. For labeling of septohippocampal projection neurons, adult Sprague-Dawley rats received injections of the fluorescent tracer Fluoro-Gold into the hippocampus 1 week prior to bilateral transection of the fimbria-fornix. After axotomy, rats were allowed to survive for varying periods ranging from 3 weeks to 18 months. Following fixation of the animals, sections through the septal region were either stained by in situ hybridization for glutamate decarboxylase (GAD) mRNA or immunostained for parvalbumin (PARV), which is known to be present in GABAergic septohippocampal neurons. In situ hybridization for GAD mRNA revealed no statistically significant changes in cell number 3 weeks and 6 months postlesion. In contrast, PARV-immunoreactive neurons were reduced to 35% of control 3 weeks postlesion. This value increased to 66% after 6 months of survival. As seen in the electron microscope, axotomized PARV-positive neurons exhibited characteristics of vital cells. Most neurons contained lysosomes associated with Fluoro-Gold, resulting from retrograde labeling prior to fimbria-fornix transection. We conclude that mainly PARV-containing GABAergic neurons in the medial septal nucleus (MS) project to the hippocampus and are thus heavily affected by the lesion but are able to survive and restore the synthesis of PARV. The lack of significant changes in the number of GAD mRNA-expressing cells is explained by the presence of numerous GABAergic MS neurons not projecting to the hippocampus.

Animals↗
PubMed1995

Evidence for corticotropin-releasing hormone projections from Barrington's nucleus to the periaqueductal gray and dorsal motor nucleus of the vagus in the rat.

The present study used anterograde and retrograde tract tracing and immunohistochemistry to determine the efferent projections of corticotropin-releasing hormone (CRH) neurons of Barrington's nucleus in the rat. Injections of Phaseolus vulgaris-leucoagglutinin into Barrington's nucleus resulted in anterograde labeling in the dorsal motor nucleus of the vagus, periaqueductal gray, medial thalamic nuclei, lateral hypothalamus, paraventricular nucleus of the hypothalamus, lateral preoptic area, and lateral septum. The retrograde tract tracer, fluorogold, injected into the lumbosacral spinal cord labeled many, but not all, CRH-immunoreactive neurons in Barrington's nucleus. Moreover, some Barrington's neurons that were retrogradely labeled from the spinal cord were not CRH-immunoreactive. Several CRH-immunoreactive Barrington's neurons were retrogradely labeled by fluorogold injections into the periaqueductal gray, and these were located predominantly in the dorsal part of the nucleus. Additionally, some CRH-immunoreactive Barrington's neurons were retrogradely labeled from fluorogold injections into the dorsal motor nucleus of the vagus. In contrast, fluorogold injections into the lateral hypothalamus, lateral preoptic area, or lateral septum did not result in double labeling of CRH-immunoreactive neurons in Barrington's nucleus. These results suggest that many, but not all, CRH-containing neurons of Barrington's nucleus project to the lumbosacral spinal cord. In addition to their previously documented projections to the spinal cord, these neurons may be a source of CRH in the periaqueductal gray and dorsal motor nucleus of the vagus. CRH projections of Barrington's nucleus may play a role in behavioral or autonomic aspects of stress responses, in addition to their proposed role in micturition.

Animals↗
PubMed1995

Monosynaptic projections from the medullary gigantocellular reticular formation to sympathetic preganglionic neurons in the thoracic spinal cord.

Microinjection of L-glutamate into a restricted area of the medullary gigantocellular reticular formation, the gigantocellular depressor area (GiDA), lowers arterial pressure. Unlike the nuclei tractus solitarii and the caudal ventrolateral medulla, the two principle medullary vasodepressor areas, the GiDA projects directly to the spinal cord and not to the rostral ventrolateral medulla (Aicher et al. [1994] Neuroscience 60:761-779). We investigated whether neurons within GiDA directly innervate autonomic areas of the thoracic spinal cord. Fluoro-Gold injected into the thoracic spinal cord labeled neurons within functionally defined vasodepressor sites in the GiDA in the same animal. To examine the morphology of GiDA efferents to the spinal cord, the anterograde tracer Phaseolus vulgaris-leucoagglutinin was iontophoresed into the GiDA, and efferent processes in the intermediolateral cell column and nucleus intercalatus spinalis were examined by electron microscopy. Labeling was confined to axons and axon terminals (n = 144) that usually contained primarily small clear vesicles, contacted large and small dendrites, and formed symmetric (inhibitory) synapses. To determine whether some of the postsynaptic targets of GiDA efferent terminals in the thoracic spinal cord were sympathoadrenal preganglionic neurons, these neurons were retrogradely labeled from the adrenal gland with Fluoro-Gold in rats that had deposits of the anterograde tracer, biotinylated dextran amine (BDA), in the GiDA. Some BDA-containing terminals formed symmetric synapses with dendrites containing Fluoro-Gold. We conclude that a population of neurons in the GiDA monosynaptically innervates some sympathetic preganglionic neurons. The findings suggest the presence of a novel reticulospinal sympathoinhibitory projection originating in the GiDA.

Adrenergic Fibers↗