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O Bosler

Publications and source records attributed to O Bosler.

At least 19 recordsLinked to original sources

Vasoactive intestinal peptide neurons as synaptic targets for vasopressin neurons in the suprachiasmatic nucleus. Double-label immunocytochemical demonstration in the rat.

Cellular relationships between neurons producing vasopressin or vasoactive intestinal peptide in the suprachiasmatic nucleus of the hypothalamus, the main component of the central circadian timing system in mammals, were investigated in the rat using double immunocytochemistry. Analysis of serial confocal images revealed that the vasopressin-synthesizing neurons not only are important targets for the vasoactive intestinal peptide-synthesizing neurons, as previously demonstrated, but also establish reciprocal axosomatic contacts with these neurons, which have never been reported. On average, 5.4 vasoactive intestinal peptide contacts per vasopressin perikaryon and 1.7 vasopressin contacts per vasoactive intestinal peptide perikaryon were counted. That both types of neurons are linked by reciprocal synapses was confirmed at the electron microscopic level using a combination of immunoperoxidase and immunogold-silver labeling. Existence of an anatomical substrate for a vasopressinergic control of the vasoactive intestinal peptide neurons may have important functional consequences. In view (i) of the presumed, direct or indirect, involvement of the vasopressin neurons in relaying pacemaker information within and outside the suprachiasmatic nucleus, and (ii) of the established role of the vasoactive intestinal peptide neurons as the main light-sensitive cells, it provides support for a neuronal mechanism through which the circadian clock may regulate inputs related to environmental messages. Our electron-microscopic data also extended earlier observations, pointing to the involvement of vasopressin and vasoactive intestinal peptide terminals in so-called double synapses that, conceivably, could regulate neuronal synchronization in the suprachiasmatic nucleus. A morphological basis for non-synaptic interactions that could be involved in ephaptic and/or paracrine communication between both types of peptidergic neurons is also reported.

Animals

Post-lesion up-regulation of 5-HT1B binding sites in the suprachiasmatic nucleus may be reversed after spontaneous or graft-induced serotonin reinnervation.

We have previously reported that selective axotomy of serotoninergic neurons produced by an intraventricular injection of 5, 7-dihydroxytryptamine is followed by an increase in 5-HT1B binding sites in the suprachiasmatic nucleus of the hypothalamus. This post-lesion up-regulation is shown here to be spontaneously reversed after long-term survival in spite of an incomplete reinnervation of the nucleus. Recovery may be accelerated by fetal raphe transplants that produce more rapid reinnervation.

Animals

Serotonin axons of the neostriatum show a higher affinity for striatal than for ventral mesencephalic transplants: a quantitative study in adult and immature recipient rats.

We previously showed that grafts of fetal ventral mesencephalic tissue are practically not innervated by host serotonin (5-HT) axons after implantation into the striatum of rats aged more than 14 days, at variance with transplants of cortical or striatal tissue into the adult striatum, which are well innervated by these axons. Using 5-HT immunohistochemistry and in vitro [3H]5-HT uptake/autoradiography, we have examined and quantified the innervation of ventral mesencephalic versus striatal grafts several months after implantation into the striatum of neonatal (postnatal day 5 or P5), juvenile (P15), and adult rats. Ventral mesencephalic grafts implanted in P5 rats received a moderate 5-HT innervation, while similar grafts implanted in P15 or adult recipients were almost free of any 5-HT fibers (-80%, compared to P5). The density of 5-HT innervation showed a tendency toward higher values in striatal than in ventral mesencephalic grafts (1.6-2 times higher in P5 and adult recipients; 4 times higher in P15 recipients). The difference was more striking, and significant, when only the true striatal portions of the striatal grafts were considered, i.e., DARPP-32-immunopositive areas (4-5 times higher in P5 and adult recipients; 10 times higher in P15 recipients). Accordingly, these DARPP-32-positive areas were also more densely innervated than the DARPP-32-negative zones of the same grafts (3 times higher at any age). The 5-HT innervation density also decreased with increasing age of the recipients in DARPP-32-positive, as well as DARPP-32-negative compartments of the striatal grafts (-75% in adults), but this decrease appeared more gradual (-50% in juveniles) than with mesencephalic grafts. It is concluded that the 5-HT axons innervating the neostriatum have a better affinity for striatal grafts than for ventral mesencephalic grafts or the nonstriatal portions of striatal grafts. In adulthood, the relative affinity of these axons for the different types of grafts is maintained, even though their growth capacity decreases irrespective of the target tissue considered. This experimental model may prove useful for the identification of the receptors and ligands that are responsible for target recognition by 5-HT axons and to test the possibility that the progressive decrease of axonal growth capacity from neonatal age to adulthood be related to a downregulation of such molecules.

Aging

Quantitative and morphometric data indicate precise cellular interactions between serotonin terminals and postsynaptic targets in rat substantia nigra.

We have quantified the density of serotonin axonal varicosities, their synaptic incidence and their distribution among potential targets in the pars reticulata and pars compacta of the rat substantia nigra. Serotonin axonal varicosities, counted at the light microscopic level following in vitro [3H]serotonin uptake and autoradiography, amounted to 9 x 10(6)/mm3 in the pars reticulata and 6 x 10(6)/mm3 in the pars compacta, among the densest serotonin innervations in brain. As determined at the electron microscopic level following immunolabelling for serotonin, virtually all serotonin varicosities in the pars reticulata and 50% of those in the pars compacta formed a synapse, essentially with dendrites. The combination of serotonin immunocytochemistry with tyrosine hydroxylase immunolabelling of dopamine neurons reveals that 20% of the serotonin synaptic contacts in the pars reticulata are on dopamine dendrites and 6% are on a type of unlabelled dendrite characterized by its peculiarly high cytoplasmic content of microtubules. The comparison of the diameter of the dendritic profiles that were in synaptic contact with serotonin-immunoreactive varicosities with the diameter of all other dendritic profiles of the same type suggests that serotoninergic varicosities innervate dopamine dendrites uniformly along their length, whereas they tend to contact microtubule-filled dendrites in more proximal regions and the other, unidentified dendrites in more distal regions. Furthermore, the size of the serotonin-immunoreactive varicosities and of their synaptic junctions is significantly smaller on dopamine dendrites and larger on microtubule-filled dendrites than on other, unidentified dendrites, indicating that the nature of the postsynaptic target is an important determinant of synaptic dimensions. These data should help to clarify the role of serotonin in the nigral control of motor functions. They indicate that this dense serotonin input to the substantia nigra is very precisely organized, acting through both "non-junctional" and "junctional" modes of neurotransmission in the pars compacta, which projects to the neostriatum and the limbic system, whereas the predominant mode of serotonin transmission appears to be of the "junctional" type in the pars reticulata, where serotonin can finely control the motor output of the basal ganglia by acting on the GABA projection neurons either directly or through the local release of dopamine by dopaminergic dendrites. The data also raise the possibility that the postsynaptic targets have trophic retrograde influences on serotoninergic terminals.

Animals

Dual character, asynaptic and synaptic, of the dopamine innervation in adult rat neostriatum: a quantitative autoradiographic and immunocytochemical analysis.

Dopamine (DA) axon terminals (varicosities) in the neostriatum of adult rats were examined for shape, size, content, synaptic incidence, type of junction, synaptic targets, and microenvironment after electron microscopic identification either by [3H]DA uptake autoradiography or by immunocytochemistry with monoclonal antibodies against DA-glutaraldehyde-protein conjugate. Both approaches yielded comparable results. Whether they were from the paraventricular or the mediodorsal neostriatum, respectively, the [3H]DA-labeled and DA-immunostained varicosities were generally oblong and relatively small; more than 60% contained one or more mitochondria. Sixty to seventy percent were asynaptic, and 30-40% were endowed with a synaptic membrane differentiation (junctional complex), as inferred by stereological extrapolation from single thin sections (both approaches) or observed directly in long, uninterrupted series of thin sections (immunocytochemistry). The synaptic DA varicosities always displayed symmetrical junctions: 67% with dendritic branches, 30% with dendritic spines, and 2-3% with neuronal cell bodies. DA varicosities juxtaposed to one another were frequent. Other axonal varicosities were more numerous in the immediate vicinity of DA varicosities than around randomly selected, unlabeled terminals. The respective microenvironments of DA and unlabeled varicosities also showed enrichment in the preferred synaptic targets of both groups of varicosities, with dendritic branches for DA and dendritic spines for the unlabeled ones. These data suggest a dual mode of operation that is diffuse as well as synaptic for the nigrostriatal DA system. In such a densely DA-innervated brain region, they also lead to the hypothesis that a basal level of extracellular DA might be maintained permanently around every tissue constituent and, thus, contribute to the mechanisms of action, properties, and functions (or dysfunctions) of DA within the neostriatum itself and as part of the basal ganglia circuitry.

Animals

Intrinsic organization and monoaminergic innervation of the suprachiasmatic nucleus transplanted to adult rats. A light- and electron-microscopic study.

Light- and electron-microscopic immunocytochemistry was used to investigate grafts of foetal hypothalamic tissue implanted close to the site of the suprachiasmatic nucleus in adult rats with bilateral surgical ablation of this nucleus. The transplants contained vasoactive intestinal peptide and vasopressin cell clusters, which have previously been shown to characterize functional suprachiasmatic nucleus grafts. Vasoactive intestinal peptide and vasopressin neurons presented synaptic features that have not been described in the native suprachiasmatic nucleus. More specifically, their terminals within the graft were involved in 'double' synapses with separate unlabelled dendrites. Moreover, in dually stained sections, an unexpected synaptic investment of vasoactive intestinal peptide neurons by vasopressin endings was detected, which revealed reversed vasoactive intestinal peptide/vasopressin interactions compared to those described in the native nucleus. These observations could reflect some immature features of the grafted neurons. Ultrastructural relationships of monoaminergic fibres arising from host and/or intragraft neurons were also examined. Within the engrafted suprachiasmatic nucleus, tyrosine hydroxylase-labelled fibres, which probably belonged to cografted dopaminergic neurons, showed normal patterns of distribution and synaptic connections, with no preferential relationships with vasoactive intestinal peptide or vasopressin neurons. Serotoninergic axons arborized within transplants but, in agreement with previous data showing an inhibitory influence of the suprachiasmatic nucleus on ingrowing serotoninergic fibres, they had no predilection for the area corresponding to that nucleus. In spite of their relative scarcity, serotoninergic fibres within the engrafted suprachiasmatic nucleus showed an almost normal synaptic incidence, but synapses were not predominantly shared with the vasoactive intestinal peptide neurons, known to be their major targets in the native nucleus. This may contribute not only to the failure of functional grafts to synchronize with environmental conditions, but also to the inability of transplants to restore hormonal rhythms such as estrous cyclicity.

Animals

Catecholaminergic innervation of the suprachiasmatic nucleus in the adult rat: ultrastructural relationships with neurons containing vasoactive intestinal peptide or vasopressin.

Catecholaminergic fibers in the suprachiasmatic nucleus of adult rats were investigated by use of light- and electron-microscopic immunocytochemistry. The suprachiasmatic nucleus receives a modest density of tyrosine hydroxylase-containing axons, homogeneously distributed in the nucleus and forming varicosities throughout its entire rostro-caudal extension. Immunolabeling with antibodies against dopamine showed that this catecholamine input comprises a dopaminergic component. Many tyrosine hydroxylase-positive cells were localized at the immediate periphery of the suprachiasmatic nucleus. With electron-microscopic examination, dendrites of these neurons were found within the limits of the nucleus as well as at a border zone between the suprachiasmatic nucleus proper and the optic tract where they received unlabeled synapses, providing a morphological support for a possible role of dopaminergic neurons in the integration and/or transfer of light-related signals. More than 91% of catecholaminergic axonal varicosities were found to establish morphologically defined synapses with dendrites. To investigate whether these synapses might be shared with neurons of one or both of the two main peptidergic populations of the nucleus, namely vasoactive intestinal peptide- and vasopressin-containing neurons, we carried out double-labelling experiments combining immunoperoxidase and immunogold-silver labeling. Results showed only a few cases of direct association of the catecholaminergic terminals with these peptidergic categories. In both types of dually stained sections, catecholaminergic synapses were preferentially made with unlabeled dendrites. The homogeneous distribution of tyrosine hydroxylase-immunoreactive fibers in the suprachiasmatic nucleus could therefore reflect a lack of significant catecholaminergic innervation of both vasoactive intestinal peptide- and vasopressin-synthesizing neurons.

Animals

Efficient immunodetection of various protein antigens in glutaraldehyde-fixed brain tissue.

Optimal ultrastructural preservation of brain tissue for electron microscopy is best achieved with fixatives containing high concentrations of glutaraldehyde, which is generally considered detrimental to the immunogenicity of most protein antigens. We tested seventeen mono- or polyclonal antibodies against peptide or protein antigens, including a majority for which immunoreactivity had previously been reported to be sensitive to glutaraldehyde fixation. Forebrain sections of rats or mice fixed by perfusion with 3.5% glutaraldehyde were processed for pre-embedding immunocytochemistry by the avidin-biotin method. The resulting immunostaining was in most cases at least similar to that obtained in sections fixed with paraformaldehyde. Immunoreactivity against the mouse or human neurofilament protein NF-L was even improved, being similar to that previously reported for unfixed brain tissue. Of all antigens tested, only choline acetyltransferase, phenylethanolamine-N-methyl transferase, and neuropeptide Y were detected with lower sensitivity than after paraformaldehyde fixation, which was attributed to a rather restricted penetration of the primary antibody into glutaraldehyde-fixed tissue sections. These results indicate that glutaraldehyde may be envisaged as a possible fixative for optimal immunocytochemical detection of any tissue antigen at the electron microscopic level, including antigens which, on the basis of results obtained after fixation with paraformaldehyde-glutaraldehyde mixtures, were considered highly sensitive to glutaraldehyde fixation.

Animals

Synaptic connectivity of serotonin graft efferents in the suprachiasmatic and supraoptic nuclei of the hypothalamus.

We have previously reported that a cell suspension from the rostral part of the embryonic raphe grafted to the basal hypothalamus of 5,7-dihydroxytryptamine-denervated rats produced incomplete serotonin (5-HT) re-innervation of the suprachiasmatic nucleus (SCN) as opposed to hyper-innervation of the supraoptic nucleus (SON). We took advantage of this experimental model to investigate whether the graft-derived, 5-HT fibres retained normal ultrastructural features, and, particularly, a normal density of synaptic junctions, irrespective of the extent of target re-innervation. The intrinsic features of immunostained, graft-derived 5-HT axonal varicosities in both the SCN (ventral portion) and the SON were essentially similar to those exhibited by the respective endogenous innervation. Analysis of well-preserved varicosities in uninterrupted series of thin sections allowed us to evaluate directly the proportions of junctional to non-junctional 5-HT varicosities in both regions. Synaptic incidences were also remarkably conserved after grafting (45.5% in the SCN versus 38.5% in the SON; 48% and 38% in normal rats, respectively). Synapses were primarily reestablished on dendritic shafts, which also were identified as the major post-synaptic targets of the normal 5-HT innervations. We noted, however, a tendency toward increased numbers of symmetrical versus asymmetrical synapses in both the SCN and SON of grafted rats. Thus, irrespective of whether hypo- or hyper-innervation patterns developed post-grafting, the transplanted 5-HT neurons essentially retained normal ultrastructural features in their target territories, with a normal incidence of synaptic junctions. The data provide further support to the hypothesis that the innervation territory is the major determinant of the frequency with which ingrowing 5-HT fibres make synaptic junctions.

5,7-Dihydroxytryptamine

Catecholaminergic projections from the solitary tract nucleus to the perifornical hypothalamus.

The source of adrenergic and other catecholaminergic fibers innervating the perifornical lateral hypothalamus was localized in the medulla after combination of Fluoro-Gold retrograde tracing and immunohistochemistry for either tyrosine-hydroxylase or phenylethanolamine-N-methyltransferase. Following perifornical injections, Fluoro-Gold-labeled neurons were observed mainly in regions including the noradrenergic and adrenergic cell groups. In the caudal solitary tract nucleus, two kinds of doubly labeled neurons were found: a) numerous noradrenergic neurons in the A2 group at the level of, or caudal to the area postrema; b) some adrenergic neurons in the C2 group at a level immediately rostral to the area postrema. These catecholaminergic neurons connecting the caudal solitary tract nucleus to the perifornical hypothalamus might convey feeding relevant information such as glycemic level or satiety signals.

Animals

Effect of changes in the intrahippocampal vasopressin on memory retrieval and relearning.

Previous results have indicated the involvement of the hippocampus in the behavioral effect of vasopressin, with a better effect when the peptide was injected in the ventral part rather than in the dorsal part of this structure. The purpose of the present study was to determine, in mice, whether the injection of vasopressin or vasopressin antisera into the ventral hippocampus has an effect on retrieval and relearning of a Go-No Go visual discrimination task and, if so, to what extent this involvement of the vasopressin system depends on the integrity of the medial amygdaloid nucleus, the main source of vasopressin innervation in the ventral hippocampus in rats. In the first experiment, we showed that pretest microinjection of Arg8-vasopressin (25 pg per animal) in the ventral hippocampus alleviated forgetting observed after a prolonged interval of 24 days between the acquisition of information and its retrieval. This enhancing effect was characterized by better retrieval and relearning in vasopressin-treated mice than those in control mice. Conversely, an immunoneutralization of endogenous vasopressin in the ventral hippocampus by the microinjection of vasopressin antisera (1/10 dilution) resulted in the drastic impairment of retrieval and relearning. Since the lack of an observable change in a locomotor activity test might explain these results, we postulated that the vasopressin system in the ventral hippocampus is involved in retrieval processes. Moreover, the effects of these treatments in a nonassociative context suggest that the effect of vasopressin could be dependent on the contextual paradigm used. In the second experiment, we localized vasopressin immunoreactive fibers in the CA1-CA2 ventral hippocampal fields and CA4-gyrus dentatus region, and vasopressin perikarya in the medial amygdaloid nucleus. Then, the projection of vasopressin cells from the medial amygdaloid nucleus to the ventral hippocampus was evaluated by studying changes in vasopressin immunoreactive fiber density in the ventral hippocampus after a lesion of the medial amygdaloid nucleus. The results showed the almost complete disappearance of vasopressin fibers in the CA1-CA2 hippocampal fields after the medial amygdaloid lesion. In contrast, vasopressin fibers in the CA4 and gyrus dentatus region remain unchanged. On the basis of our immunohistochemical results, our third experiment tested the repercussions of the change in vasopressin innervation in the ventral hippocampus, due to the medial amygdaloid lesion, on the effects of exogenously administered vasopressin on both retrieval and relearning processes. The medial amygdaloid lesion induced a deleterious effect on retrieval without really affecting the ability to relearn. No observable change in locomotor activity could explain this impairment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Convergent serotonin and GABA innervation of VIP neurons in the suprachiasmatic nucleus demonstrated by triple labeling in the rat.

By means of a combination of serotonin (5-HT) uptake radioautography and dual immunocytochemistry, vasoactive intestinal polypeptide (VIP) neurons in the suprachiasmatic nucleus are demonstrated to simultaneously receive both 5-HT and GABA afferents at their somatic and dendritic levels. These data constitute a further step towards the improved characterization of the morphological substrate of the integrative function of these neurons, which are known to play an important role in the delivery of light-mediated rhythmic signals to other parts of the brain.

Animals

Long-term serotonin reinnervation of the suprachiasmatic nucleus after 5,7-dihydroxytryptamine axotomy in the adult rat.

We present here immunohistochemical evidence that serotonin (5-HT) reinnervation in the suprachiasmatic nucleus (SCN) of adult rats, after intraventricular administration of 5,7-dihydroxytryptamine, is more extensive than formerly believed. The first fibers appeared at 4 months and developed until more than 7 months. However, comparison with age-matched controls showed that, even 24 months post-lesion, the density of 5-HT innervation remained abnormally low. At the electron microscopic level, many synaptic contacts were found to have been re-established. The cellular mechanisms possibly responsible for incomplete 5-HT reinnervation in the SCN are discussed.

5,7-Dihydroxytryptamine

Co-localization of tyrosine hydroxylase, GABA and neuropeptide Y within axon terminals innervating the intermediate lobe of the frog Rana ridibunda.

Possible co-existence of gamma-aminobutyric acid (GABA), catecholamines, and neuropeptide Y (NPY) in the same nerve terminals of the frog intermediate lobe was investigated by immunocytochemistry at the electron microscopic level. Co-localization of GABA and tyrosine hydroxylase (TH) was studied by using a double immunogold labeling procedure. Co-localization of glutamate decarboxylase (GAD) and NPY was studied by combining, respectively, the peroxidase-antiperoxidase method and a radioimmunocytochemical labeling procedure. Catecholamines and GABA were systematically co-localized in nerve endings of the pars intermedia. Most of the NPY-immunoreactive fibers also contained GAD-like immunoreactivity. However, a few NPY-positive nerve terminals were not immunoreactive for GAD. These data provide evidence for co-existence of a regulatory peptide (NPY) and several neurotransmitters (i.e., GABA and catecholamines) within the same axon terminals in the intermediate lobe. Since GABA, dopamine, and NPY have all been shown to inhibit the activity of frog melanotrope cells, the present findings suggest that these neuroendocrine factors may interact either at the pre-synaptic or post-synaptic level.

Animals

Association of neurotensin receptors with VIP-containing neurons and serotonin-containing axons in the suprachiasmatic nucleus of the rat.

The aim of the present study was to identify cellular elements bearing high-affinity neurotensin (NT) binding sites in the suprachiasmatic nucleus (SCN) of the rat hypothalamus. Because the distribution of these binding sites had previously been reported to conform to that of both vasoactive intestinal peptide (VIP)-containing nerve cell bodies and serotonin (5-HT)-containing axons, the following experimental approaches were used: (1) the overlap between autoradiographically labeled NT binding sites and immunocytochemically labeled VIP neurons was examined in adjacent 5-microns-thick sections taken across the entire rostrocaudal extent of the SCN; and (2) the density of NT binding sites was examined by quantitative autoradiography following cytotoxic lesioning of 5-HT afferents. Double-labeling studies demonstrated precise overlap between 125I-NT binding and VIP immunostaining throughout the SCN. Moreover, at high magnification intensely VIP-immunoreactive neurons were found in direct register with 125I-NT-labeled cells visualized in adjacent sections. Densitometric autoradiographic studies demonstrated a significant reduction in specific 125I-NT binding within the SCN following intracerebroventricular injection of the neurotoxin, 5,7-dihydroxytryptamine. Taken together, these results indicate that within the SCN, NT receptors are present both presynaptically on serotonin axons and postsynaptically on the perikarya and dendrites of VIP-containing neurons.

5,7-Dihydroxytryptamine

Dual immunocytochemistry using 125I-labeled protein A: a new electron microscopic technique applied to the investigation of chemical connectivity and axonal transmitter co-localization in the brain.

We have developed a double labeling immunocytochemical method utilizing peroxidase conjugated Fab fragments and 125I-labeled protein A to localize two neuronal markers on the same light or electron microscopic section with primary antibodies raised in the same animal species. The technique is applicable to the study of chemical connectivity in the brain, as illustrated by data obtained in the hypothalamus using rabbit polyclonal antisera against tyrosine hydroxylase (TH), phenylethanolamine-N-methyltransferase (PNMT), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP). Moreover, due to a high level of sensitivity and resolution, the technique offers considerable advantages over many previously developed dual labeling immunocytochemical methods for the demonstration of transmitter axonal co-localizations. Utilizing the peroxidase Fab/[125I]protein A method, we present here the first direct evidence that PNMT is present in many endings also containing NPY in the thalamic and hypothalamic paraventricular nuclei and in the arcuate nucleus. The method also may be combined as required with other labeling methods for localizing more than two neurochemical markers on one and the same electron microscopic section.

3,3'-Diaminobenzidine

Serotonin reinnervation of the rat organum vasculosum laminae terminalis (OVLT) after 5,7-dihydroxytryptamine deafferentation.

The time course and pattern of serotonin (5-HT) reinnervation in the rat organum vasculosum laminae terminalis (OVLT) following intracerebroventricular administration of 5,7-dihydroxytryptamine were examined by means of [3H]5-HT uptake radioautography. 5-HT axonal varicosities reappeared in the OVLT within 3 months post-lesion. Six months later, they were found to have preferentially reinvested the neurohemal contact area (juxtavascular zone) of the organ. Regenerated terminals further increased in number. At the end of a 16-month survival time, they displayed normal-looking distributional patterns, similar to those of age-matched control animals, and formed new synaptic junctions in the juxtaventricular zone. The cellular mechanisms possibly responsible for 5-HT recovery in the OVLT are discussed.

5,7-Dihydroxytryptamine

Adrenergic innervation of noradrenergic locus coeruleus neurons. A dual labeling immunocytochemical study in the rat.

By means of dual immunocytochemistry, synaptic associations between adrenergic terminals and noradrenergic neurons were directly demonstrated in the rat locus ceruleus (LC). It could be estimated that every adrenergic afferent contacts at least one noradrenergic dendrite in the nucleus. An adrenergic innervation of non-noradrenergic targets was also evidenced. These data add to our knowledge on the synaptic circuitry by which activation of the adrenergic input could affect central mechanisms known to be influenced by LC neurons.

Adrenergic Fibers