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H J Groenewegen

Publications and source records attributed to H J Groenewegen.

At least 19 recordsLinked to original sources

Regional and cellular distribution of serotonin 5-hydroxytryptamine2a receptor mRNA in the nucleus accumbens, olfactory tubercle, and caudate putamen of the rat.

This paper describes the regional and cellular distribution of serotonin 5-hydroxytryptamine2a (5-HT2a) receptor mRNA in (sub)regions of the rat striatum by using in situ hybridization. Our results indicate that 5-HT2a mRNA is distributed heterogeneously in this brain region. Regional densitometry of autoradiograms from striatal sections hybridized with isotope-labeled cRNA probes showed that mRNA levels were highest in the olfactory tubercle, lower in the nucleus accumbens, and lowest in the caudate-putamen. In the nucleus accumbens, the average mRNA levels in the shell were higher than those in the core. These data suggest a particular relevance for the 5-HT2a receptor for olfactory tubercle- and shell-related functions. Therefore, in the nucleus accumbens and the olfactory tubercle, the cellular localization of 5-HT2a mRNA was investigated by determining the colocalization of 5-HT2a mRNA with enkephalin mRNA or dynorphin mRNA. 5-HT2a mRNA was found in enkephalinergic as well as dynorphinergic neurons. Thus, there does not seem to be a differential distribution of this receptor in the output routes of the ventral striatum. In all of the subregions investigated (core, medial shell, and lateral shell of the nucleus accumbens and the olfactory tubercle), only subpopulations of the total enkephalinergic and dynorphinergic populations were found to contain 5-HT2a mRNA. For enkephalin, the percentage colocalization was higher in the lateral shell (61%) compared with the other subregions (38-45%). For dynorphin, the percentage colocalization was higher in the olfactory tubercle (68%) than in the other subregions (34-43%). The differences in (sub)regional mRNA levels and in colocalization with opioids suggest a considerable regional differentiation in the effects of 5-HT2a-mediated neurotransmission in the striatum.

Animals

Injection of dye into neurones in rat and human post-mortem brain, in combination with acetylcholinesterase histochemistry: permanent preparations.

We describe a protocol for the intracellular injection of dye into neurones in thick sections of fixed, post-mortem rat and human brain tissue. To render the sections with the intracellularly injected neurones permanent, they are sectioned again, and the resulting subsections are either immunocytochemically treated or stained histochemically for acetylcholinesterase (AChE) activity. The resultant preparations can be stored at room temperature for prolonged periods. Background staining produced by accumulation of erythrocytes in blood vessels is greatly reduced or virtually eliminated by exposure of the sections to ultraviolet radiation prior to the intracellular injection. The pattern of AChE staining is not affected by this procedure. This ability to stain sections according to a histochemical AChE procedure after the intracellular injection of dyes into striatal neurons opens the possibility to study the relationship of neuronal dendritic trees with the striosome/matrix compartmental boundaries in post-mortem (human) brain tissue of Huntington's disease patients.

Acetylcholinesterase

Morphology of the human internal vertebral venous plexus: a cadaver study after intravenous Araldite CY 221 injection.

Reviewing the literature on the vascular anatomy of the spinal epidural space, it appeared that the knowledge of the internal vertebral venous plexus is limited. Injection studies of the entire internal vertebral venous plexus after application of modern techniques, to the best of our knowledge, have never been performed. Based on the clinical importance of these structures, it was decided to study the human vertebral venous system after Araldite CY 221 injection, in order to update the morphological characteristics of the internal vertebral venous system. The vertebral venous systems of ten fresh human cadavers, between 64 and 93 years of age, were injected with Araldite CY 221 mixture. All cadavers were dissected and the posterior and anterior internal vertebral venous plexuses were studied in detail. The anterior part of the internal vertebral venous plexus is fairly constant. On the contrary, the posterior internal vertebral venous plexus showed a striking segmental and interindividual variability. In the thoracic area, two types of traversing veins are observed. Both types show a somewhat symmetrical "inversed V" configuration. No anatomical valves were observed. Nevertheless, anterograde flushing (via the femoral veins) of the vertebral venous system appeared to proceed much faster than retrograde flushing (via the superior vena cava). The classical picture of the internal vertebral venous plexus appears a simplification of the actual situation. Especially in the posterior part, segmental and interindividual differences are prominent. The preferential direction of the flow during flushing suggests the presence of functional valves, which are probably located in the thoracic part of the posterior internal vertebral venous plexus, resulting from the typical shape of the veins in this area. This might explain the difficulties with imaging of the posterior part of the internal vertebral venous plexus in vitro as well as in vivo. Further study is needed to determine whether the configuration of the posterior internal vertebral venous plexus in younger individuals is different, compared with the presently studied aged subjects.

Aged

The accumbens: beyond the core-shell dichotomy.

This article highlights recent discoveries related to the accumbens and closely associated structures, with special reference to their importance in neuropsychiatry. The development of "striatal patches" in the accumbens is reviewed in a series of pictures. Neuronal ensembles are discussed as potentially important functional-anatomical units. Attention is also drawn to recent discoveries related to the neuronal circuits that the primate accumbens establishes with the mesencephalic dopamine system. On the basis of histological and neurochemical differences, the accumbens has been divided into core and shell compartments. In the context of this article, the shell, which is an especially diversified part of the accumbens, is the subject of special attention because of its close relation to the extended amygdala and distinctive response to antipsychotic and psychoactive drugs.

Animals

The anatomical relationships of the prefrontal cortex with limbic structures and the basal ganglia.

This paper briefly discusses the anatomical criteria that have been used to delineate the prefrontal cortex (PFC) from the (pre)motor cortical areas in the frontal lobe. Single anatomical criteria, such as cytoarchitecture, connectivity with the mediodorsal thalamic nucleus or a dopaminergic innervation, are insufficient to unequivocally define the PFC. It is argued that, with respect to a number of structural aspects, the prefrontal and the (pre)motor cortical areas must be viewed as a continuum, whereas a (functional) differentiation is based on the type of information that is being processed in different parts of the frontal lobe. The involvement of the PFC, like the premotor cortex, in a number of basal ganglia-thalamocortical circuits may be interpreted in the same way. The paper also summarizes the organization of the inputs from midline/intralaminar thalamic nuclei, the basal amygdaloid complex and the hippocampus into the PFC-ventral striatal system. The results of tracing studies in rats indicate that these thalamic and limbic inputs both at the level of the PFC and the ventral striatum show various patterns of convergence and segregation. This leads to the conclusion that the PFC-ventral striatal system consists of a number of smaller modules.

Amygdala

Basal amygdaloid complex afferents to the rat nucleus accumbens are compartmentally organized.

The basal amygdaloid complex (BAC) topographically projects to the nucleus accumbens (Acb) in patchy, inhomogeneous patterns. These termination patterns may be related to the histological features of the Acb that define the shell, core, and adjacent ventral caudate-putamen (CPv), and the ventral striatal compartments providing output to different autonomic, motor, and endocrine targets. Knowledge of the relationships of BAC afferents with these compartments is essential for understanding the activities of amygdalostriatal circuits. Therefore, anterograde tracing experiments were performed, combined with calbindin-D28K (CaB) immunohistochemistry or Nissl staining. The results demonstrated that the caudal parvicellular basal amygdala (Bpc) projected primarily to cell clusters in the dorsal shell of the medial Acb, and to patches in the core/CPv. Fibers from the caudal accessory basal nucleus (AB) selectively reached CaB-immunoreactive cell clusters in the ventral shell, avoiding the core/CPv. The rostral AB projected to the same ventral shell compartments as the caudal AB; in addition, dense terminations were found in the matrix of the core/CPv, avoiding the patches. Caudal magnocellular basal amygdala (Bmg) fibers reached ventral parts of the shell, including the CaB-immunoreactive cell clusters. The caudal Bmg projected strongly to the patches of the core/CPv, evading the matrix. Finally, the rostral Bmg densely innervated the moderately CaB-immunoreactive lateral shell and the patches of the core/CPv, largely avoiding the matrix. These results indicate the specific compartmental relationships of the patchy BAC terminations and suggest that BAC subregions differentially influence particular ventral striatal outputs.

Amygdala

Shell and core in monkey and human nucleus accumbens identified with antibodies to calbindin-D28k.

The neurochemical division of the rodent nucleus accumbens into shell and core is now a widely accepted concept. However, such divisions in the primate nucleus accumbens have yet to be fully clarified and described. In the present study, the forebrains of three primates--marmoset, rhesus monkey, and human--and a Wistar rat, were immunoreacted with antibodies directed against calbindin-D28k. The patterns of immunoreactivity in the primates' ventral striatum were mapped and compared to that of rat. Calbindin staining was uneven in all species and there was no evidence of a bicompartmental organization, i.e., striosome/patch and matrix, in central parts of the nucleus. Nucleus accumbens in primates, as in rat, could be divided immunohistochemically into a crescent-shaped outer shell--medially, ventrally and laterally--and an inner core. In general, medial parts of the shell stained less intensely for calbindin than did lateral parts. However, interspecific variation in the intensity of the immunoreactive staining and the mediolateral extent of the shell was obvious. The core, which immunostained unevenly, was consistently more intensely immunoreactive than either medial or lateral shell in all species except the marmoset. These results suggest that the neurochemical subdivisions of shell and core established for nucleus accumbens of rodents are also present in primates. However, further work is needed to establish whether these territories are homologous and, if so, the full extent of that homology.

Animals

Patterns of overlap and segregation between insular cortical, intermediodorsal thalamic and basal amygdaloid afferents in the nucleus accumbens of the rat.

Regions of the prefrontal cortex that project to the nucleus accumbens in the rat receive input from midline thalamic and basal amygdaloid nuclei which also project to the same striatal region as their prefrontal cortical target. For example, the prelimbic cortex projects to the medial nucleus accumbens, and receives input from the paraventricular thalamic nucleus and the parvicellular basal amygdala. These latter two areas also project to the medial nucleus accumbens. It has been shown that afferents from the prelimbic cortex, the paraventricular thalamic nucleus and the parvicellular basal amygdala to the nucleus accumbens overlap or are separated in the nucleus accumbens, depending upon their position in the shell and core. The dorsal agranular insular cortex, the intermediodorsal thalamic nucleus and the magnocellular basal amygdaloid nucleus terminate in the lateral part of the nucleus accumbens and adjacent ventral part of the caudate-putamen. The intermediodorsal thalamic nucleus and the magnocellular basal amygdaloid nucleus reach both the dorsal agranular insular cortex and the lateral nucleus accumbens, and thus appear positioned to influence the prefrontal corticostriatal system at cortical and striatal levels. However, all three afferent systems have a heterogeneous distribution within this striatal region, and whether these projections actually reach the same areas is unknown. We investigated the patterns of separation and overlap in the nucleus accumbens between dorsal agranular insular cortical, magnocellular basal amygdaloid and intermediodorsal thalamic afferents with respect to the histochemical features of the nucleus. Techniques allowing the detection of two different anterograde tracers, or a single anterograde tracer and Calbindin-D28k immunoreactivity, in the same tissue sections were used. The results demonstrate that the afferents from the dorsal agranular insular area and the intermediodorsal thalamic nucleus avoid the shell of the lateral nucleus accumbens, which receives strong inputs from the magnocellular basal amygdala. In the matrix of the core and the ventral part of the caudate-putamen, fibers from the superficial layers of the dorsal agranular insular area overlap precisely with afferents from the intermediodorsal nucleus. In the patches, projections from the deep layers of the dorsal agranular insular cortex coincide with those from the magnocellular basal amygdala. The present findings have implications for the compartmental structure of the nucleus accumbens and provide novel insights into the organizational principles of prefrontal corticostriatal circuits.

Afferent Pathways

Efferent projections of the retrorubral nucleus to the substantia nigra and ventral tegmental area in cats as shown by anterograde tracing.

The aim of the present study was to determine whether the retrorubral nucleus projects to the dopaminergic nuclei in the ventral midbrain of the cat. For this purpose, injections of biotinylated dextran-amine or Phaseolus vulgaris-leucoagglutinin were placed into the retrorubral nucleus under stereotaxic guidance. The tracers were visualized by means of (immuno) histochemical procedures. In addition, tyrosine hydroxylase immunohistochemistry was used to evaluate the location of the injection sites and the distribution of the anterogradely labeled fibers. Both tracers reveal the same topography of labeled fibers in the ventral mesencephalon. Labeled fibers with varicosities were found ipsilaterally in the substantia nigra pars compacta, the substantia nigra pars lateralis, the ventral tegmental area and, contralaterally, in the substantia nigra pars compacta, the ventral tegmental area, and the retrorubral nucleus. A considerable number of labeled axons with varicosities were observed to be wrapped around the dendrites and perikarya of tyrosine hydroxylase-positive neurons in these areas. The present results are discussed in view of the possible role of the A8 dopaminergic cell group in the coordination of A9 nigrostriatal and A10 mesolimbic systems, as well as in the progressive pathology seen in patients suffering from Parkinson's disease.

Animals

Patterns of convergence and segregation in the medial nucleus accumbens of the rat: relationships of prefrontal cortical, midline thalamic, and basal amygdaloid afferents.

In the rat, fibers from the prelimbic cortex terminate in the medial nucleus accumbens. Anterior paraventricular thalamic and parvicellular basal amygdaloid fibers reached both the prelimbic cortex and the medial nucleus accumbens. All three afferent systems have an inhomogenous distribution within the nucleus accumbens, and whether or not these projections actually reach the same areas is unknown. Our aim was to evaluate the relationships of the three afferents with respect to the shell, the core, and the cell clusters of the nucleus accumbens. Double anterograde tracing and single anterograde tracing combined with immunohistochemistry for calbindin (D28k) or Nissl stain was used. Following tracer injections in the prelimbic cortex and the anterior paraventricular thalamus, a complementary (i.e., nonoverlapping) pattern of fibers was found in the shell. Thus, afferents from the prelimbic cortex are associated with cell clusters, whereas those from the anterior paraventricular thalamus avoid these cells but are affiliated with regions exhibiting weak homogeneous calbindin immunoreactivity. In the calbindin-poor patches of the core, the situation is reversed as both sets of fibers overlap. In cases with injections in the prelimbic cortex and the parvicellular basal amygdala, a pattern of overlap was seen in the shell and core. Thus, the fibers in the shell were found together in association with cell clusters, whereas regions of weak homogeneous calbindin immunoreactivity were avoided. In the core, overlap was seen in the patch compartment. Finally, with parvicellular basal amygdala/paraventricular thalamus injections, a complementary fiber organization was present in the shell, but overlap was prominent in the patches of the core. The results demonstrate that the relationships of prelimbic cortical, paraventricular thalamic, and parvicellular basal amygdaloid afferents in the nucleus accumbens vary according to their compartmental (immunohistochemical and cellular) affiliation. Compartmentalization is therefore a possible anatomical substrate for condensation or segregation of neuronal signals passing through the nucleus accumbens.

Afferent Pathways

Effects of unilateral 6-hydroxydopamine lesions on neuropeptide immunoreactivity in the basal ganglia of the common marmoset, Callithrix jacchus, a quantitative immunohistochemical analysis.

Previous immunocytochemical studies in rats have indicated that striatal dopamine depletion leads to an increase in enkephalin-immunoreactivity and a decrease in substance P-immunoreactivity in the striatum. Similar studies in primates have lead to contradictory results. In the present study changes in tyrosine hydroxylase-, met-enkephalin- and substance P-immunoreactivity were determined in the basal ganglia of 6 common marmosets Callithrix jacchus following dopamine depletion by unilateral intracerebral 6-hydroxydopamine (6-OHDA) injections using three different survival times. The non-lesioned side served as an intra-individual control. Tyrosine hydroxylase immunoreactivity was strongly reduced in the entire ipsilateral striatum. Enkephalin-immunoreactivity was increased throughout the striatum. Substance P-immunoreactivity was significantly increased in only one case in the caudate nucleus and in two cases in the putamen, while in other cases either a non-significant increase or decrease was found. Therefore, the results of the present study indicate that in marmosets dopamine has a inhibiting effect on the levels of striatal enkephalin, while its effect on substance P (SP) appears to be absent.

Animals

Immunohistochemical characterization of the shell and core territories of the nucleus accumbens in the rat.

The nucleus accumbens in the rat has been parcelled into shell and core subdivisions. Despite accumulating evidence for such a division of the nucleus accumbens, these territories have not been delineated throughout the rostrocaudal extent of the nucleus. In the present study, an attempt has been made to delineate the shell and core using the distribution of calcium-binding protein immunoreactivity, substance P immunoreactivity and acetylcholinesterase activity in transverse and horizontal sections through the nucleus accumbens. It was found that the pattern of calcium-binding protein immunoreactivity provides the most unequivocal criterion to divide the nucleus accumbens into a ventral and medial, peripheral shell displaying low to moderate immunostaining, and a more laterally and dorsally located, strongly stained inner core. In most parts of the nucleus, borders seen in the calcium-binding protein immunoreactivity pattern can also be recognized in the distributions of substance P immunoreactivity and acetylcholinesterase activity. It is concluded that the shell occupies most of the rostral part of the nucleus accumbens, whereas rostrally the core is represented only in the most lateral part. Differences in staining intensities for all three markers indicate that both the shell and core have a heterogeneous structure. Patterns of connectivity appear to support the division of the nucleus accumbens as indicated by calcium-binding protein immunoreactivity in the present study.

Acetylcholinesterase

The specificity of the 'nonspecific' midline and intralaminar thalamic nuclei.

The midline and intralaminar thalamic nuclei have long been considered to be a 'nonspecific' nuclear complex that relays the activity of the brain-stem reticular formation to widespread cerebral-cortical areas. Over the past decade, it has become clear that individual midline and intralaminar nuclei each receive specific sets of afferents and project to specific parts of the cerebral cortex and striatum. Moreover, the targets of the thalamocortical and thalamostriatal projections of a given nucleus are interconnected through corticostriatal projections. Therefore, the midline and intralaminar nuclei might have a dual role in corticosubcortical interactions in the forebrain. Through distinct sets of inputs to individual midline or intralaminar thalamic nuclei, these nuclei are in a position to interact selectively with particular, functionally segregated basal-ganglia-thalamocortical circuits. By way of nonselective inputs, in particular from cholinergic brain-stem nuclei, the midline and intralaminar nuclei might act in concert to modify the level of activity of the entire basal-ganglia-thalamocortical system.

Animals

Differential effects of dopamine depletion on the binding and mRNA levels of dopamine receptors in the shell and core of the rat nucleus accumbens.

In the present study, using quantitative receptor autoradiography and in situ hybridization histochemistry the effects of unilateral 6-hydroxydopamine lesions on the binding density levels of dopamine D1 and D2 receptors and the levels of mRNA encoding D1 and D2 receptors were investigated in the core and shell territories of the nucleus accumbens (Acb) and in the caudate-putamen (CP). The lesions induced contrasting effects on the D1 binding and D1 mRNA in the Acb and CP, i.e. an increase in binding and a decrease in the mRNA levels. For the D2 receptor an increase in both the binding density and mRNA levels was observed. The lesion-induced effects displayed regional differences. For D1 mRNA and D1 and D2 binding, the lesion effect was more pronounced in the core than in the shell of the Acb. For the D2 mRNA levels an increase was observed in the CP but not in the two territories of the Acb. Furthermore, the decrease in D1 mRNA was greater in the rostral than in the caudal parts of the core and shell of the Acb. These results indicate that the core and shell of the Acb and the CP respond differentially to dopamine depletion.

Animals

Evidence for a multi-compartmental histochemical organization of the nucleus accumbens in the rat.

In the present study, the compartmental organization of the nucleus accumbens was investigated by comparing the pattern of leu-enkephalin immunoreactivity with that of the opioid receptor ligand, naloxone, an established marker for the compartmental organization of the neostriatum. Both patterns have a nonhomogeneous, patch-like appearance throughout the rostrocaudal extent of the nucleus and show a good, mutual correspondence. In the core of the nucleus accumbens as well as in the border region between the nucleus accumbens and the caudate-putamen, leu-enkephalin-rich areas are in register with opioid receptor-dense areas. In the shell region the precise relationship between the enkephalin and the naloxone patterns could not be established. A comparison of the connectivity patterns and neurochemical characteristics of the opioid receptor-dense compartments in the nucleus accumbens with those in the caudate-putamen reveals major discrepancies between these two striatal subdivisions. We therefore conclude that, rather than a bicompartmental patch/striosome-matrix organization, the nucleus accumbens has a multicompartmental organization.

Animals