Common limbic and frontal-striatal disturbances in patients with obsessive compulsive disorder, panic disorder and hypochondriasis.

BACKGROUND: Direct comparisons of brain function between obsessive compulsive disorder (OCD) and other anxiety or OCD spectrum disorders are rare. This study aimed to investigate the specificity of altered frontal-striatal and limbic activations during planning in OCD, a prototypical anxiety disorder (panic disorder) and a putative OCD spectrum disorder (hypochondriasis). METHOD: The Tower of London task, a 'frontal-striatal' task, was used during functional magnetic resonance imaging measurements in 50 unmedicated patients, diagnosed with OCD (n=22), panic disorder (n=14) or hypochondriasis (n=14), and in 22 healthy subjects. Blood oxygen level-dependent (BOLD) signal changes were calculated for contrasts of interest (planning versus baseline and task load effects). Moreover, correlations between BOLD responses and both task performance and state anxiety were analysed. RESULTS: Overall, patients showed a decreased recruitment of the precuneus, caudate nucleus, globus pallidus and thalamus, compared with healthy controls. There were no statistically significant differences in brain activation between the three patient groups. State anxiety was negatively correlated with dorsal frontal-striatal activation. Task performance was positively correlated with dorsal frontal-striatal recruitment and negatively correlated with limbic and ventral frontal-striatal recruitment. Multiple regression models showed that adequate task performance was best explained by independent contributions from dorsolateral prefrontal cortex (positive correlation) and amygdala (negative correlation), even after controlling for state anxiety. CONCLUSIONS: Patients with OCD, panic disorder and hypochondriasis share similar alterations in frontal-striatal brain regions during a planning task, presumably partly related to increased limbic activation.

[Impulse control disorders in Parkinson's disease]. / Impulscontrolestoornissen bij de ziekte van Parkinson en de relatie tot andere stoornissen binnen het impulsieve-compulsieve spectrum.

BACKGROUND: Parkinson's disease is characterised not only by the classic triad of bradykinesia, rigidity and tremor, but also by the frequent occurrence of various non-motor symptoms such as the impulse control disorders (pathological gambling, hypersexuality, compulsive buying, binge eating, punding and dopamine dependency). AIM: To increase insight into the clinical presentation, risk factors, treatment and the underlying pathophysiological mechanisms of impulse control disorders in Parkinson's disease. METHOD: Relevant literature was reviewed. RESULTS: Impulse control disorders belong to an important group of neuropsychiatric disorders that occur at some point in 5-10% of patients with Parkinson's disease. They generally occur in conjunction with dopaminergic medication and can have a marked social, relational and/ or financial impact. CONCLUSION: Early recognition of impulse control disorders in Parkinson's disease is important and a close collaboration between the neurologist and the psychiatrist is essential in order to ensure correct diagnosis and the best possible treatment. Impulse control disorders in Parkinson's disease show considerable phenomenological overlap with other repetitive behaviours within the impulsive-compulsive spectrum of disorders to which the obsessive-compulsive disorders and addiction disorders belong. The overlap can possibly be explained by a shared pathophysiological mechanism involving an imbalance between the direct and indirect pathways of the dorsal and ventral frontal-striatal circuits.

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.

Intrinsic connections of the cingulate cortex in the rat suggest the existence of multiple functionally segregated networks.

The cingulate cortex is a functionally and morphologically heterogeneous cortical area comprising a number of interconnected subregions. To date, the exact anatomy of intracingulate connections has not been studied in detail. In the present study we aimed to determine the topographical and laminar characteristics of intrinsic cingulate connections in the rat, using the anterograde tracers Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine. For assessment of these data we further refined and compared the existing cytoarchitectonic descriptions of the two major cingulate constituents, the anterior cingulate and retrosplenial cortices. The results of this study demonstrate that rostral areas, i.e. the infralimbic and prelimbic cortices and the rostral one third of the dorsal anterior cingulate cortex are primarily interconnected with each other and not with other cingulate areas. The caudal two thirds of the dorsal anterior cingulate cortex project to the caudal part of the ventral anterior cingulate cortex, whereas the entire ventral anterior cingulate cortex projects to only the mid-rostro-caudal part of the dorsal anterior cingulate cortex. Dense reciprocal connections exist between the remaining, i.e. the supracallosal parts of the anterior cingulate and retrosplenial cortices with a general rostro-caudal topography, in the sense that the rostral part of the anterior cingulate cortex and caudal part of the retrosplenial cortex are interconnected and the same holds true for the caudal part of the anterior cingulate cortex and rostral part of the retrosplenial cortex. This topographical pattern of intracingulate connections relates to the results of several functional studies, suggesting that specific cingulate functions depend on a number of interconnected cingulate subregions. Through their intricate associational connections, these subregions form functionally segregated networks.

Bilateral control of brain activity by dopamine D1 receptors: evidence from induction patterns of regulator of G protein signaling 2 and c-fos mRNA in D1-challenged hemiparkinsonian rats.

Recent reports show that striatal dopamine D1-type receptors from one side of the normal rat brain can control brain activity (as measured by c-fos induction) on both sides of the brain. However, this phenomenon has not yet been studied in the presence of sensitized dopamine D1-type receptors. Here we address this issue by investigating the extent to which dopamine D1-type receptors control brain activation in rats with unilaterally sensitized dopamine D1-type receptors. Gene induction assays were used to identify activated regions from midbrain to forebrain in unilaterally 6-hydroxydopamine lesioned (hemiparkinsonian) rats challenged with the full dopamine D1-type agonist SKF82958 (3 mg/kg, 0.5 and 2 h). The genes used are c-fos, the proven neuronal activity marker, and Regulator of G protein Signaling 2, a gene we propose as a marker of signaling homeostasis. SKF82958-mediated induction of both genes is greatly enhanced in hemiparkinsonian rats compared with shams, in both the lesioned and the intact hemisphere. For example, in the denervated caudate-putamen at 2 h postinjection, this enhancement is more than 80-fold for c-fos and up to 20-fold for Regulator of G protein Signaling 2; for the intact side this is 35-fold for c-fos and 27-fold for Regulator of G protein Signaling 2. Cortical induction of c-fos and Regulator of G protein Signaling 2 was generalized to most neocortical regions and was essentially equivalent in both the denervated and intact hemispheres. Interestingly, hippocampal structures also showed strong bilateral induction of both genes. This overall pattern of brain activation can be accounted for by the basal-ganglia thalamocortical and hippocampal circuits which both contain hemisphere-crossing connections and which can be initially activated in the lesioned hemisphere. Some regions, such as the intact striatum or the CA1 region, showed relatively low c-fos induction and relatively high Regulator of G protein Signaling 2 induction, possibly indicating that these regions are engaged in unusually strong signaling regulation activities. Our results show that, besides basal ganglia-thalamocortical circuits, dopamine D1-type-mediated brain activation in hemiparkinsonian rats also involves hippocampal circuits.

Anatomical evidence for direct connections between the shell and core subregions of the rat nucleus accumbens.

The nucleus accumbens is thought to subserve different aspects of adaptive and emotional behaviors. The anatomical substrates for such actions are multiple, parallel ventral striatopallidal output circuits originating in the nucleus accumbens shell and core subregions. Several indirect ways of interaction between the two subregions and their associated circuitry have been proposed, in particular through striato-pallido-thalamic and dopaminergic pathways. In this study, using anterograde neuroanatomical tracing with Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine as well as single-cell juxtacellular filling with neurobiotin, we investigated the intra-accumbens distribution of local axon collaterals for the identification of possible direct connections between the shell and core subregions. Our results show widespread intra-accumbens projection patterns, including reciprocal projections between specific parts of the shell and core. However, fibers originating in the core reach more distant areas of the shell, including the rostral pole (i.e. the calbindin-poor part of the shell anterior to the core) and striatal parts of the olfactory tubercle, than those arising in the shell and projecting to the core. The latter projections are more restricted to the border region between the shell and core. The density of the fiber labeling within both the shell and core was very similar. Moreover, specific intrinsic projections within shell and core were identified, including a relatively strong projection from the rostral pole to the rostral shell, reciprocal projections between the rostral and caudal shell, as well as projections within the core that have a caudal-to-rostral predominance. The results of the juxtacellular filling experiments show that medium-sized spiny projection neurons and medium-sized aspiny neurons (most likely fast-spiking) contribute to these intra-accumbens projections. While such neurons are GABAergic, the intrastriatal projection patterns indicate the existence of lateral inhibitory interactions within, as well as between, shell and core subregions of the nucleus accumbens.

Connections of the parahippocampal cortex. I. Cortical afferents.

In the present study in the cat the parahippocampal cortex denotes the caudoventral part of the limbic lobe and is composed of the entorhinal and perirhinal cortices. The cytoarchitecture of these areas and their borders with adjacent cortical areas are briefly discussed. The organization of the cortical afferents of the parahippocampal cortex was studied with the aid of retrograde and anterograde tracing techniques. In order to identify the source of cortical afferents, injections of retrograde tracers such as wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP), or the fluorescent substances fast blue or nuclear yellow, were placed in different parts of the parahippocampal cortex. In an attempt to further disclose the topographical and laminar organization of the afferent pathways, injections of tritiated amino acids were placed in cortical areas that were found to project to the parahippocampal cortex. The results of these experiments indicate that fibers from olfactory-related areas, the hippocampus, and other parts of the limbic cortex project only to the entorhinal cortex. The afferents from olfactory structures terminate predominantly superficially, whereas hippocampal and limbic cortical afferents are directed mainly to layers deep to the lamina dissecans. Paralimbic areas, including the anterior cingulate and the prelimbic cortices on the medial aspect, and the orbitofrontal and granular and agranular insular cortices on the lateral aspect of the hemisphere, project to the entorhinal cortex and medial parts of area 35 of the perirhinal cortex. These mostly mesocortical afferents terminate in both the superficial and deep layers of the entorhinal and perirhinal cortices. Parasensory association areas, which form part of the neocortex, do not project farther medially in the parahippocampal cortex than the perirhinal areas 35 and 36. These afferents mainly stem from a rather wide rim of neocortex that lies directly adjacent to area 36 and extends from the posterior sylvian gyrus via the posterior ectosylvian gyrus into the posterior suprasylvian gyrus. There is a rostrocaudal topographical arrangement in these projections such that rostral cortical areas distribute more rostrally and caudal parts project to more caudal parts of the perirhinal cortex. The cortex of the posterior suprasylvian gyrus contains the paravisual areas 20 and 21. The posterior sylvian gyrus most probably represents a para-auditory association area, whereas the most ventral part of the posterior ectosylvian gyrus may constitute a convergence area for visual and auditory inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

Connections of the parahippocampal cortex in the cat. II. Subcortical afferents.

The organization of subcortical inputs to the parahippocampal cortex, which in the present study in the cat is considered to comprise the entorhinal and perirhinal cortices, was studied by using retrograde and anterograde tracing techniques. The results of the retrograde tracer horseradish peroxidase (HRP), HRP conjugated with wheat germ agglutinine (WGA-HRP), Fast Blue (FB) or Nuclear Yellow (NY] injections indicate that the entorhinal and perirhinal cortices receive inputs from the magnocellular basal forebrain and from distinct portions of the amygdaloid complex, the claustrum, and the thalamus. The two cortices are further projected upon by fibers from the supramamillary region of the hypothalamus, the ventral tegmental area of the mesencephalon, the dorsal raphe nucleus, the nucleus centralis superior, and the locus coeruleus. The entorhinal cortex, in addition, receives projections from the medial septum. As regards the projections from the amygdaloid complex, it was observed that the entorhinal cortex receives its heaviest input from the basolateral amygdaloid nucleus, whereas the perirhinal cortex receives a strong projection from the lateral nucleus and a weaker projection from the basomedial nucleus of the amygdala. Of the thalamic nuclei that project to the parahippocampal cortex, the nucleus reuniens is only connected with the entorhinal cortex, while fibers from the medial geniculate nucleus and the lateral posterior nucleus terminate in the perirhinal cortex. Injections of tritiated amino acid (3H-leucine) were placed in the medial septum, the dorsal and ventral claustrum, the basolateral and basomedial amygdaloid nuclei, and the nucleus reuniens of the thalamus. The results of these experiments demonstrate that, with the exception of the claustrum, these subcortical areas project mainly to the superficial layers I-III and the lamina dissecans of the parahippocampal cortex, and to a lesser degree to the deep layers V and VI.

Connections of the parahippocampal cortex in the cat. III. Cortical and thalamic efferents.

To study the distribution of the cortical and thalamic efferent projections from the parahippocampal cortex in the cat, a series of injections of anterogradely transported radioactively labeled amino acids were placed in different parts of the entorhinal and perirhinal cortices. Subsequently, some of the identified cortical and thalamic target areas were injected with retrograde tracers such as wheat germ-agglutinin conjugated with horseradish peroxidase (WGA-HRP) or with a fluorescent tracer--fast blue or nuclear yellow--in order to disclose the laminar origin of the parahippocampal efferent projections. The results indicate that the parahippocampal cortex gives rise to widespread projections to the association cortex, and, to a lesser extent, sends fibers to the limbic cortex and the primary sensory cortex. These projections arise mainly from the deep layers of the parahippocampal cortex and terminate predominantly in superficial layers of the cortex, with a preference for layer I. Within the cortical projections a medial-to-lateral topography could be observed such that the entorhinal cortex projects predominantly to the allocortical and periallocortical limbic areas, including parts of the subicular complex, the ventral retrosplenial and the infralimbic cortices, and olfactory related areas--i.e., the olfactory bulb, the anterior olfactory nucleus, the prepiriform cortex, and the ventral tenia tecta. The more lateral parts of the parahippocampal cortex, which surround the posterior rhinal sulcus, project in addition to extensive parts of the paralimbic association cortex that include the proisocortical cingular, prelimbic, orbitofrontal, and agranular and granular insular cortices. The most lateral portion of the parahippocampal cortex, the perirhinal cortex, furthermore issues projections to widespread neocortical areas on the lateral and medial aspects of the hemisphere that constitute part of the parasensory association cortex. Weak-to-moderate projections are found to the cortex of the middle suprasylvian and anterior ectosylvian sulci, as well as the cruciate and splenial sulci, all of which have been reported to constitute sensory convergence areas. The most marked projections from the perirhinal cortex reach a zone of neocortex directly lateral to the perirhinal cortex including ventral parts of the posterior sylvian, posterior ectosylvian, posterior suprasylvian, and lateral gyri. These projections appear to be topographically organized such that rostral parts of the perirhinal cortex project more rostrally, and more caudal parts of the perirhinal cortex project to more caudal parts of this cortical zone.(ABSTRACT TRUNCATED AT 400 WORDS)

Connections of the parahippocampal cortex in the cat. IV. Subcortical efferents.

The present report deals with the projections from the entorhinal and perirhinal cortices to subcortical forebrain structures and the brainstem in the cat. By using anterograde and retrograde tracing techniques, it could be demonstrated that the entire mediolateral extent of the parahippocampal cortex issues prominent projections to the dorsal and ventral striatum, the amygdala, and the claustrum. In addition, the entorhinal cortex sends projections to the septum and the diagonal band of Broca. Only the perirhinal cortex gives rise to a weak projection to the dorsolateral periaquaductal gray and the ventral pontine region. The major proportion of the subcortical projections originates in the perirhinal cortex and the lateral entorhinal cortex, whereas the medial entorhinal cortex has a much sparser output and sends no fibers to the amygdala. The subcortical projections from both the entorhinal cortex and the perirhinal cortex arise mostly from their deep layers. It was further found that these projections are topographically organized along the mediolateral axis of the parahippocampal cortex. This mediolateral axis is related to a ventrolateral to dorsomedial axis in the septum, a mediolateral axis in the amygdala and the ventral striatum, and a ventrodorsal coordinate in the dorsal striatum and the claustrum. A further topography was observed in the projections from the perirhinal cortex to the lateral amygdaloid nucleus. A rostrocaudal axis in the perirhinal cortex corresponds to a mediolateral axis in the lateral amygdaloid nucleus. The present observations are compared with data concerning the connectivity of the parahippocampal cortex with the hippocampal formation and other cortical structures. It is suggested that the parahippocampal cortex in the cat may be conceptualized as an interface between the hippocampal formation and several subcortical structures in the realm of the limbic and motor systems.

Interrelationship of the distribution of neuropeptides and tyrosine hydroxylase immunoreactivity in the human substantia Nigra.

The relationship in the human substantia nigra of peptidergic fibers with intrinsic dopaminergic neurons was studied in adjacent coronal sections of the mesencephalon immunohistochemically stained for enkephalin (ENK), substance P (SP), and tyrosine (TH) hydroxylase immunoreactivity. TH-positive elements are present in the substantia nigra in at least two different arrangements: 1) a dorsal tier of rather loosely arranged neurons, which is continuous medially with the ventral tegmental area and laterally with the retrorubral area, 2) a ventral tier of more closely packed neurons, clusters of which frequently form finger-like extensions deep into the pars reticulata. This ventral region contains TH-positive dendrites extending ventrally into the pars reticulata. The distribution of ENK is mainly restricted to the medial half of the ventral aspect of the substantia nigra, while SP occupies its entire rostral-caudal and medial-lateral extents. Peptide-positive fibers vary in density from dense to light. There is very little overlap between the dorsal tier of the TH-positive neurons and the ENK or SP staining. The dorsal part of the peptide-immunoreactive area extensively overlaps with the TH-positive neurons of the ventral tier of cells. The ventral part of the peptide-positive area overlaps with the pars reticulata of the substantia nigra in which the TH-positive dendrites extend. The overlap between the neuropeptide fibers and the TH-positive cells of the ventral tier is not complete, with cells found both within and outside peptide-positive fiber networks. Three patterns of overlap emerge. In dorsal regions elongated cell clusters lie partially within and partially outside the dense peptide-positive fiber networks. In the ventral regions TH-positive cells are either completely embedded within peptide fibers or clusters of cells are present in peptide-free zones. These data suggest that specific peptidergic pathways differentially innervate the substantia nigra. TH cells which lie within or outside these fibers may reflect functionally different subsystems in the striatonigral pathways in the human.

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.

The parasagittal zonation within the olivocerebellar projection. I. Climbing fiber distribution in the vermis of cat cerebellum.

After lesions of inferior olive, survival times of 5 to 12 days and Nauta staining, degeneration is present in white matter and central cerebellar nuclei and Deiters' nucleus. Shorter survival times from 40 to 60 hours and Fink-Heimer impregnantion reveal degenerating climbing fiber terminals in the molecular layer. With 3H-leucine autoradiography and survival times of three to seven days the entire trajectory of the climbing fibers can be traced. Olivocerebellar fibers cross in the brain stem and terminate contralaterally in cortex and central nuclei. Occasional labeling of mossy fiber terminals is explained by involvement of reticular nuclei. Small parts of the inferior olive connect with narrow longitudinal zones in the cortex through compartments in the white matter. The corresponding distribution of olivocerebellar fibers and Purkinje cell axons over these compartments suggests that the organization of the olivocerebellar and corticonuclear projection is essentially similar. Collaterals always terminate in the central cerebellar nucleus which receives a corticonuclear projection from the zone in which the parent fibers terminate. Caudal medial accessory olive projects to medial vermal zone A and to fastigial nucleus, subnucleus beta projecting to lobule VII and caudal fastigial nucleus. Caudal dorsal accessory olive projects to lateral vermal zone B in lobules I-VI, Deiters' nucleus and dorsomedial subnucleus of interposed nucleus. The caudal principal olive (dorsal cap, ventrolateral outgrowth receiving visual and vestibular input) projects to flocculo-nodular lobe.

Laminar origin and septotemporal distribution of entorhinal and perirhinal projections to the hippocampus in the cat.

The projections of the entorhinal and perirhinal cortices to the hippocampus in the cat have been studied with retrograde and anterograde tracing techniques. Retrogradely transported tracers, which were injected at different levels along the septotemporal longitudinal hippocampal axis, result in labeled neurons in superficial entorhinal cortical layers II and III. Occasionally, labeled cells were also observed in the deepest entorhinal layer as well as in the superficial layers of the perirhinal area 35. It could further be shown that labeled neurons located superficially in the entorhinal cortex are topographically distributed in a lateromedial gradient, which corresponds to a septotemporal gradient along the longitudinal axis of the hippocampus. This topographical organization of the entorhinal-hippocampal projection system could be substantiated by the use of anterograde tracing of radioactively labeled amino acids. Injections in the entorhinal cortex produce labeled fibers in the hippocampus. Injections in the perirhinal area 35 result also in labeling over the hippocampus, whereas area 36 does not seem to distribute fibers to the hippocampus. As anticipated from the results of the retrograde tracing experiments, injections located laterally, in or close to the posterior rhinal sulcus, produce prominent labeling over the septal pole of the hippocampus, whereas progressively more medially located injections result in progressively more temporally located labeling. This topographical distribution of perforant path fibers along the septotemporal axis of the hippocampus, which is related to a lateromedial axis in the entorhinal cortex, has been observed following injections in the lateral entorhinal area (LEA) as well as in the medial entorhinal area (MEA). The present observations are discussed in regard of other connectional and putative functional differences between the septal and temporal hippocampus.

Organization of the efferent projections of the nucleus accumbens to pallidal, hypothalamic, and mesencephalic structures: a tracing and immunohistochemical study in the cat.

The efferent connections of the nucleus accumbens in the cat were studied with the aid of anterograde and retrograde tracing techniques. The description of the topography of these projections to pallidal, hypothalamic, and mesencephalic areas is preceded by a redefinition of the borders of the pallidal regions in the cat, using immunohistochemical criteria. In agreement with previous studies in rat and monkey substance-P-like and enkephalinlike immunoreactivity in the pallidum of the cat appears to be present in so-called "woolly fibers." Substance-P- and enkephalin-positive woolly fibers are differentially distributed in the internal and external segments of the globus pallidus, as traditionally defined, but are both present in the rostral part of the substantia innominata, here called the "ventral pallidum." Woolly fibers are also found in a number of other basal telencephalic structures and in the rostral part of the lateral hypothalamic area. Fibers from the medial part of the nucleus accumbens distribute to the ventral pallidum and to the just-mentioned area in the rostral part of the lateral hypothalamus, which most probably represents part of the internal segment of the globus pallidus. The medial nucleus accumbens projects in addition to the lateral septum, the bed nucleus of the stria terminalis, the medial preoptic and hypothalamic areas, the ventral tegmental area, the retrorubral nucleus, the central superior nucleus, the nucleus tegmenti pedunculopontinus, and the central gray. The lateral part of the nucleus accumbens projects to the ventral pallidum, the subcommissural part of the globus pallidus, the entopeduncular nucleus, the substantia nigra, and the retrorubral nucleus.

Connections of the subthalamic nucleus with ventral striatopallidal parts of the basal ganglia in the rat.

The present study was undertaken to establish the precise anatomical relationship of the subthalamic nucleus (STh) with limbic lobe-afferented parts of the basal ganglia in the rat. The anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L), injected in the STh, the globus pallidus, the ventral pallidum, the ventral striatum, and the parafascicular thalamic nucleus, and the retrograde tracers Fluoro-Gold (FG) and cholera toxin B (CTb), injected in the globus pallidus, the ventral pallidum, the ventral striatum, and the ventral mesencephalon, were used for this purpose. The results of these tracing experiments confirm the general notion of reciprocal connections between the STh and pallidal areas. Thus the dorsomedial part of the STh is connected with the subcommisural ventral pallidum, whereas a more ventral and lateral part of the medial STh is related to the medial globus pallidus. The lateral hypothalamic area, directly adjacent to the STh, containing neurons with a morphology quite similar to those in the STh, projects to parts of the ventral pallidum related to the olfactory tubercle. The reciprocal projection from this pallidal area to subthalamic regions appears to be very sparse. The medial STh sends strong projections to the medial part of the entopeduncular nucleus and the adjacent lateral hypothalamic area. Sparser projections from the medial STh reach the rostral and medial part of the caudate-putamen and the nucleus accumbens. The nucleus accumbens sends a very sparse projection back to the medial STh. The projections of the medial STh to the ventral mesencephalon appear also to be topographically organized. The lateral hypothalamus and a few cells in the most medial part of the STh project to the ventral tegmental area, whereas progressively more lateral parts of the ventral mesencephalon, in particular the substantia nigra, receive input from successively more lateral and caudal parts of the STh. In addition, a number of STh fibers reach the midbrain extrapyramidal area. The lateral part of the parafascicular thalamic nucleus projects to the lateral part of the STh, whereas parafascicular neurons medial to the fasciculus retroflexus project to the dorsomedial portion of the STh. The medial part of the STh and the adjacent lateral hypothalamus are intimately connected with limbic parts of the basal ganglia in a way similar and parallel to the connections of the lateral STh with motor-related parts of the basal ganglia. These findings suggest a role for the STh in nonmotor functions of the basal ganglia.

Organization of the thalamostriatal projections in the rat, with special emphasis on the ventral striatum.

The organization of the thalamic projections to the ventral striatum in the rat was studied by placing injections of the retrograde tracer cholera toxin subunit B in the ventral striatum and small deposits of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in individual midline and intralaminar thalamic nuclei. In order to provide a complete map of the midline and intralaminar thalamostriatal projections, PHA-L injections were also made in those parts of the intralaminar nuclei that project to the dorsal striatum. The relationship of thalamic afferent fibres with the compartmental organization of the ventral striatum was assessed by combining PHA-L tracing and enkephalin immunohistochemistry. The various midline and intralaminar thalamic nuclei project to longitudinally oriented striatal sectors. The paraventricular thalamic nucleus sends most of its fibres to medial parts of the nucleus accumbens and the olfactory tubercle, whereas smaller contingents of fibres terminate in the lateral part of the nucleus accumbens and the most ventral, medial, and caudal parts of the caudate-putamen complex. The projections of the parataenial nucleus are directed towards central and ventral parts of the nucleus accumbens and intermediate mediolateral parts of the olfactory tubercle. The intermediodorsal nucleus projects to lateral parts of the nucleus accumbens and the olfactory tubercle and to ventral parts of the caudate-putamen. The projection of the rhomboid nucleus is restricted to the rostrolateral extreme of the striatum. A diffuse projection to the ventral striatum arises from neurons ventral and caudal to the nucleus reuniens rather than from cells inside the nucleus. Fibres from the central medial nucleus terminate centrally and dorsolaterally in the rostral part of the nucleus accumbens and medially in the caudate-putamen. Successively more lateral positions in the caudate-putamen are occupied by fibres from the paracentral and central lateral nuclei, respectively. The lateral part of the parafascicular nucleus projects to the most lateral part of the caudate-putamen, whereas projections from the medial part of this nucleus terminate in the medial part of the caudate-putamen and in the dorsolateral part of the nucleus accumbens. Furthermore, a rostral to caudal gradient in a midline or intralaminar nucleus corresponds to a dorsal to ventral and rostral to caudal gradient in the striatum. In the ventral striatum, thalamic afferent fibres in the "shell" region of the nucleus accumbens avoid areas of high cell density and weak enkephalin immunoreactivity.(ABSTRACT TRUNCATED AT 400 WORDS)

Compartmental organization of the ventral striatum of the rat: immunohistochemical distribution of enkephalin, substance P, dopamine, and calcium-binding protein.

In the caudate-putamen of the rat a patch/matrix organization can be recognized on the basis of the immunohistochemical distribution of several markers, which include enkephalin, substance P, dopamine, and calcium-binding protein. In the present experiments the distributional relations of these markers were investigated in the nucleus accumbens. The distribution of enkephalin fibers shows different inhomogeneities according to their location in the nucleus. Rostrally, heavily labeled areas stand out against a moderately stained background, whereas caudally, in medial and ventral parts of the nucleus, lightly stained areas delineate regions in the moderately stained neuropil. In the distribution of substance P, areas with high staining intensity were observed in the medial and ventral parts of the nucleus accumbens. Inhomogeneities in the distribution of strong dopamine immunoreactivity consist of weakly immunoreactive areas throughout the rostrocaudal extent of the nucleus accumbens and extremely heavily labeled areas in the medial and ventral parts of the nucleus. Calcium-binding protein immunoreactivity can only be detected in dorsal parts of the nucleus. The generally intense immunostaining for calcium-binding protein is interspersed with "blanks" of weak immunoreactivity. The heavily and moderately labeled enkephalin areas each maintain specific relations with inhomogeneities in the distribution of substance P, dopamine, and calcium-binding protein. Rostrally, the heavily labeled enkephalin areas coincide with areas strongly immunostained for calcium-binding protein and with lightly stained areas in the dopamine and substance P immunoreactivity patterns. In the same region lightly stained areas in the enkephalin distribution match heavily labeled substance P areas. Caudally, in the border region of the nucleus accumbens and the caudate-putamen, the heavily labeled enkephalin areas are either related to "blanks" or to the intense staining regions in the calcium-binding protein immunoreactivity distribution. The moderately labeled enkephalin areas caudomedially in the nucleus accumbens are in register with the heavily labeled regions in the distribution of substance P and with the extremely heavily labeled regions in the distribution of dopamine. Relations with connectivity are discussed and the inhomogeneities are compared to those in the caudate-putamen. It is concluded that in the ventral striatum either one patch and one matrix compartment exist with different immunohistochemical relationships or there are several compartments with different immunohistochemical characteristics and different input-output relations.

The parasagittal zonation within the olivocerebellar projection. II. Climbing fiber distribution in the intermediate and hemispheric parts of cat cerebellum.

Olivocerebellar fibers from different subnuclei of the rostral inferior olive decussate in the brain stem and terminate as climbing fibers in one or two narrow, longitudinally arranged zones of the cerebellar cortex. These fibers issue collaterals to the central cerebellar nucleus that receives its afferents from the same cortical zone in which the parent fibers terminate. The rostral medial accessory olive projects to zone C2 and sends collaterals to the posterior interposed nucleus. A differentiation can be made between the rostral pole of this subnucleus which projects primarily to the paraflocculus and the ansiform lobule. More caudal areas connect with zone C2 in the anterior lobe and the paramedian lobule. The dorsomedial cell column projects to a lateral zone (zone A2) of lobule IX and more rostrolateral portions of the medial accessory olive supply a still more lateral zone of this lobule. The rostral half of the dorsal accessory olive sends fibers to zones C1 and C3. These fibers issue collaterals to the anterior interposed nucleus. A distinction can be made between the ventrolateral dorsal accessory olive, projecting to lobules II-IV and the ventral folia of the paramedian lobule and the dorsomedial portion of the rostral dorsal accessory olive that connects with lobules V, VI and the dorsal folia of the paramedian lobule. The most rostral part of the dorsal accessory olive provides more fibers into zone C3, more caudally located cells distribute primarily to zone C1. The rostral principal olive is connected with zone D and collateral terminations are found in the lateral cerebellar nucleus. In the paraflocculus the D zone can be divided into subzones D1 and D2. This study further substantiates the similarity in the organization of corticonuclear and olivocerebellar connections. The results are in general agreement with other recent investigations on the olivocerebellar system (Armstrong et al., '74; Brodal et al., '75; Brodal, '76; Hoddevik et al., '76; Brodal and Walberg, '77a,b; Oscarsson, '73, '76; Oscarsson and Sjölund, '77a,b).

The dorsal column nuclear projections to the nucleus ventralis posterior lateralis thalami and the inferior olive in the cat: an autoradiographic study.

This autoradiographic study demonstrates a topical projection of the dorsal column nuclei to the contralateral nucleus ventralis posterior lateralis thalami and the accessory part of the inferior olive. In contrast to earlier anatomical studies the projections of the gracile nucleus and the internal cuneate nucleus proved to be independent and entirely contralateral. Fibers from the gracile nucleus terminate only in the lateral part of the nucleus ventralis posterior lateralis (VPL1) and from the internal cuneate nucleus only in the medial part of this nucleus (VPLm). Projections of the gracile nucleus to the contralateral inferior olive are restricted to the caudal one-third of the medial accessory olive and the ventrolateral part of the dorsal accessory olive. The internal cuneate nucleus is only connected with the dorsomedial part of the rostral two-thrids of the dorsal accessory olive. Our material does not allow conclusions about projections from the dorsal column nuclei to other thalamic nuclei and about rostrocaudal point to point relationships between the dorsal column nuclei and the thalamus or the inferior olive.