The nigrostriatal pathway: axonal collateralization and compartmental specificity.

This paper reviews two of the major features of the nigrostriatal pathway, its axonal collateralization, and compartmental specificity, as revealed by single-axon labeling experiments in rodents and immunocytological analysis of human postmortem tissue. The dorsal and ventral tiers of the substantia nigra pars compacta harbor various types of neurons the axons of which branch not only within the striatum but also in other major components of the basal ganglia. Furthermore, some nigrostriatal axons send collaterals both to thalamus and to brainstem pedunculopontine tegmental nucleus. In humans, the compartmental specificity of the nigrostriatal pathway is revealed by the fact that the matrix compartment is densely innervated by dopaminergic fibers, whereas the striosomes display different densities of dopaminergic terminals depending on their location within the striatum. The nigral neurons most severely affected in Parkinson's disease are the ventral tier cells that project to the matrix and form deep clusters in the substantia nigra pars reticulata.

Chemical architecture of the posterior striatum in the human brain.

The neurochemical organization of the posterior caudate nucleus (CN) (body, gyrus and tail) and putamen (Put) was analyzed in the human brain using adjacent sections stained for acetylcholinesterase (AChE), limbic system-associated membrane protein (LAMP), enkephalin (ENK), parvalbumin (PV), calbindin (CB) and tyrosine hydroxylase (TH). Striosomes were visualized in all striatal regions but the anterior two thirds of the CN tail. They were highly immunoreactive (-ir) for ENK and LAMP, devoid of PV and AChE staining, and surrounded by a ring of tissue with pale TH- and CB-ir neuropil. In the Put, other rings of tissue completely free of ENK labeling surrounded certain striosomes (clear septa). In the CN body, gyrus and tail some markers revealed gradients and heterogeneities along the dorsoventral and mediolateral axes. A rim of striatal tissue densely stained for ENK and LAMP and poorly labeled for PV was noticeable along the lateral edge of the Put and the dorsolateral sector of the CN body. Our results illustrate a chemical architecture in the posterior striatum that is heterogeneous and slightly different from that found in the more anterior striatum.

[The amygdaloid complex and its implication in psychiatric disorders]. / El complejo amigdalino humano y su implicación en los trastornos psiquiátricos.

The amygdaloid complex is a group of nuclei located deep in the temporal lobe and closely involved in the limbic system. Its alteration has been associated with some psychiatric processes. In this article, an overall review was made of the published data concerning the amygdaloid complex in the most common psychiatric diseases. A damaged amygdaloid complex is commonly observed, that in the Klüver-Bucy syndrome presents the fullest expression. A decrease in the amygdaloid complex of schizophrenic patients has been observed. This finding was found bilaterally in men whereas in women it was only located in one hemisphere. This finding suggests that morphometric alterations in the amygdaloid complex are more diffuse and more severe in men with schizophrenia. This subcortical complex is larger in children with autism, but not in adolescents, in whom the amygdaloid complex volume matches the normal volume of an adolescent or an adult without this pathology. However, neuroanatomical studies have shown microscopic alterations. In patients with mood disorders, it has been reported that the left amygdaloid complex presents a lesser volume. Moreover, in frontotemporal dementia and Alzheimer disease a slight amygdaloid atrophia was found related to the healthy controls. It can be concluded that the amygdaloid complex is involved in several psychiatric processes, due to structural or functional damage. However, more studies are still needed in order to delimitate the real influence of the amygdaloid complex in these disorders.

Chemical parcellation of the anterior thalamic nuclei in the human brain.

The anterior thalamic nuclei (ATN) encompass a large region of the anteromedial aspect of the human thalamus. Three ATN have been classically described: anteroventral (AV), anteromedial (AM) and anterodorsal (AD). The present study has carried out histochemical and immunohistochemical procedures in the ATN of normal individuals to analyze whether these nuclei are chemically distinct. The markers used in this study were acetylcholinesterase (AChE), limbic system-associated membrane protein (LAMP), the calcium binding proteins calbindin D-28k (CB), parvalbumin (PV), and calretinin (CR), and the neuropeptides substance P (SP) and enkephalin (ENK). Other cytoarchitectural and myeloarchitectural techniques, specifically Nissl and Gallyas stainings, were used to delineate the boundaries of the ATN. The main findings of this study are: 1) AChE was very abundant in the AD and was irregular or heterogeneously distributed in the AV and AM; 2) LAMP immunoreactive (ir) neuropil was present throughout the ATN and its distribution was heterogeneous in the AV and AM; 3) the ATN harbored CB-, PV- and CR-ir neurons and neuropil; and, 4) the neuropeptide analysis revealed numerous SP positive varicose fibers scattered throughout the ATN in contrast to very few ENK-ir varicose fibers. These morphological findings describe a heterogeneous chemical anatomy in the human ATN which may reflect regional differences in the functional organization of the ATN with respect to the other thalamic nuclei and the cerebral cortex.

Barrel pattern formation requires serotonin uptake by thalamocortical afferents, and not vesicular monoamine release.

Thalamocortical neurons innervating the barrel cortex in neonatal rodents transiently store serotonin (5-HT) in synaptic vesicles by expressing the plasma membrane serotonin transporter (5-HTT) and the vesicular monoamine transporter (VMAT2). 5-HTT knock-out (ko) mice reveal a nearly complete absence of 5-HT in the cerebral cortex by immunohistochemistry, and of barrels, both at P7 and adulthood. Quantitative electron microscopy reveals that 5-HTT ko affects neither the density of synapses nor the length of synaptic contacts in layer IV. VMAT2 ko mice, completely lacking activity-dependent vesicular release of monoamines including 5-HT, also show a complete lack of 5-HT in the cortex but display largely normal barrel fields, despite sometimes markedly reduced postnatal growth. Transient 5-HTT expression is thus required for barrel pattern formation, whereas activity-dependent vesicular 5-HT release is not.

Striatal input from the ventrobasal complex of the rat thalamus.

We have analyzed whether caudal regions of the caudate putamen receive direct projections from thalamic sensory relay nuclei such as the ventrobasal complex. To this aim, the delivery of the retrograde neuroanatomical tracer Fluoro-Gold into the caudal caudate putamen resulted in the appearance of retrogradely labeled neurons in the ventral posteromedial and ventral posterolateral thalamic nuclei. These projections were further confirmed with injections of the anterograde tracers biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin into these thalamic nuclei, by showing the existence of axonal terminal fields located in the caudal striatum. These results support the existence of direct projections linking the thalamic ventrobasal complex and the caudal striatum in the rat, probably via collateralization of thalamocortical axons when passing through the caudate putamen, and therefore supporting the putative involvement of the caudal striatum in sensory-related functions.

Thalamic distribution of zinc-rich terminal fields and neurons of origin in the rat.

Several cortico-cortical and limbic-related circuits are enriched in zinc, which is considered as an important modulator of glutamatergic transmission. While heavy metals have been detected in the thalamus, the specific presence of zinc has not been examined in this region. We have used two highly sensitive variations of the Timm method to study the zinc-rich innervation in the rat thalamus, which was compared to the distribution of acetylcholinesterase activity. The origin of some of these zinc-rich projections was also investigated by means of retrograde transport after intracerebral infusions of sodium selenium (Na2SeO3). The overall zinc staining in the thalamus was much lower than in the neocortex, striatum or basal forebrain; however, densely stained terminal fields were observed in the dorsal tip of the reticular thalamic nucleus, the anterodorsal and lateral dorsal thalamic nuclei and the zona incerta. In addition, moderately stained zinc-rich terminal fields were found in the rostral intralaminar nuclei, nucleus reuniens and lateral habenula. Intracerebral infusions of Na2SeO3 in the lateral dorsal nucleus resulted in retrogradely labeled neurons that were located in the postsubiculum, and also in the pre- and parasubiculum. These results are the first to establish the existence of a zinc-rich subicular-thalamic projection. Similar infusions in either the intralaminar nuclei or the zona incerta resulted in labeling of neurons in several brainstem structures related to the reticular formation. Our results provide morphological evidence for zinc modulation of glutamatergic inputs to highly selective thalamic nuclei, arising differentially from either cortical limbic areas or from brainstem ascending activation systems.

Double retrograde tracer study of the corticostriatal projections to the cat caudate nucleus.

The distribution of corticostriatal neurons projecting to the caudate nucleus was examined in the cat by retrograde fluorescent tracers. Thus, Fast Blue and Diamidino Yellow were concomitantly injected in different rostrocaudal, dorsoventral, or mediolateral sectors of the caudate nucleus. The main findings of this study are: 1) few double-labeled cells were found after two injections in different sectors of the caudate nucleus; 2) double-labeled neurons were more abundant after adjacent injections and they were mainly located in 6 alpha beta, dorsolateral prefrontal, dorsomedial prefrontal, prelimbic, anterior limbic, sylvian anterior, and rostral part of cingulate cortical areas; and 3) there were variations in the spatial organization of the corticostriatal neurons in different cortical areas projecting to various parts of the caudate nucleus.

[The use of the impact index as a quality measure in research]. / Algunas reflexiones sobre la utilización del índice de impacto como medida de calidad en la investigación.

In this article some considerations are made upon the use of the impact factor as a measure for the quality in research. A historical view of the term "impact factor" is presented together with other aspects to keep in mind when the impact factor is used as a measure of citations. In addition, some criticisms are pointed out in the use of the impact factor as a tool to evaluate the quality of research, funding, employment and tenure.

Complex brain circuits studied via simultaneous and permanent detection of three transported neuroanatomical tracers in the same histological section.

Experimental neuroanatomical tracing methods lie at the basis of the study of the nervous system. When the scientific question is relatively straightforward, it may be sufficient to derive satisfactory answers from experiments in which a single neuroanatomical tracing method is applied. In various scientific paradigms however, for instance when the degree of convergence of two different projections on a particular cortical area or subcortical nucleus is the subject of study, the application of single tracing methods can be either insufficient or uneconomical to solve the questions asked. In cases where chains of projections are the subjects of study, the simultaneous application of two tracing methods or even more may be compulsory. The present contribution focuses on combinations of several neuroanatomical tract-tracing strategies, enabling in the end the simultaneous, unambiguous and permanent detection of three transported markers according to a three-color paradigm. A number of combinations of three tracers or of two tracers plus the immunocytochemical detection of a neuroactive substance can be conceived; we describe several of these combinations implemented by us using the present multitracer protocol.

Considerations on the thalamostriatal system with some functional implications.

The thalamostriatal projections are largely neglected in current reviews dealing with basal ganglia function. In the past few years, however, several studies have re-evaluated these projections and have postulated their implication in more complex tasks within the basal ganglia organization. In this review, we try to focus on the morphological and functional importance of this system in the basal ganglia of the rat, cat and monkey. Special attention is paid to the thalamus as an important place for interaction between the input and the output systems of the basal ganglia through the thalamostriatal projections. Thus, we stress on the overlapping thalamic territories between the thalamic projection of the output nuclei of the basal ganglia and the thalamostriatal neurons. Our experimental data support the existence of several thalamic feedback circuits within the basal ganglia functional design. Finally, some considerations are provided upon the functional significance of these thalamic feedback circuits in the overall organization of the basal ganglia in health and disease.

[Functional anatomy of the cerebral cortex implicated in visual processing]. / Anatomía funcional de la corteza cerebral implicada en los procesos visuales.

INTRODUCTION AND OBJECTIVE: The functional anatomy of the cerebral cortex implicated in vision is reviewed with the purpose of illustrating the complexity of the cortical processing in visual perception. DEVELOPMENT: A brief analysis of the retinogeniculocortical pathway is presented and a summary of the main findings of the physiological and anatomical studies of Hubel and Wiesel in the adult brain is also illustrated. Special attention is paid in showing the visual pathways for object and face recognition as well as spatial cognition. CONCLUSIONS: Visual cortical areas in primates and man can be divided roughly into a ventral stream in relation with the temporal lobe responsible for the processing and storage of information about the identity of objects, their shape, color, and other salient physical features; and a dorsal stream in relation with the parietal lobe and concerned with the analysis of the locations of objects, and their movements in space. These two cortical pathways are not totally segregated and both are related to the prefrontal cortex as well as other subcortical structures such as the thalamus, the basal ganglia, the superior colliculus and the cerebellum through the pontine nuclei.

Considerations upon the anatomical model of reward-based learning in the basal ganglia.

The nigrostriatal pathway appears to be very important in the reward-based learning. The dopaminergic neurons in the substantia nigra pars compacta (SNC) fire in relation to primary rewards and reward-conditioned stimuli, but not to rewards that are expected. It has been hypothesized that the anatomical framework for the selective response of these neurons is organized in the projections from some paralimbic areas in the frontal lobe to the striosomes of the caudate nucleus, which are also directly connected with the dopaminergic neurons of the SNC. Here, we present two additional pathways that may be related with this neurophysiological finding. We hypothesize that the connections of the paralimbic cortices with the ventral system of the basal ganglia and then with the thalamus and the hypothalamus, and the circuit ventral striatum-substantia nigra pars reticulata-thalamus-striatum could be also involved in the reward-based learning.

Anatomical re-evaluation of the corticostriatal projections to the caudate nucleus: a retrograde labeling study in the cat.

The distribution of cortical neurons projecting to the cat caudate nucleus (CN) was examined using retrograde labeling methods. Single injections of either horseradish peroxidase conjugated with wheat germ agglutinin (HRP-WGA), or the fluorescent tracers Fast Blue (FB) or Diamidino Yellow (DY) were made into different regions of the CN. This study confirms the following previous findings. (1) Labeled neurons were observed in the frontal and parieto-temporal cortices. (2) The corticocaudate cells were mainly located in layer V, although some cells were also observed in layer III and occasionally in layers II and VI. (3) Dorsal injections into the rostral CN yielded more dorsal labeling in the cerebral cortex. However, ventral cortical areas such as the ventral part of the prelimbic (PL) cortical area and the insular cortex (sylvian anterior (SA), agranular and disgranular insular areas) presented retrograde labeling after both dorsal and ventral injections into the CN. (4) Dorsal injections into the CN labeled all subdivisions of areas 4 and 6 whereas the ventral ones labeled only the areas 4delta, 6alphabeta, 6aalpha, 6iffu. The novel findings of this study are as follows. (1) The cortical area 6betabeta and the dorsolateral prefrontal area (PfDl) were labeled in all our cases. In addition, PL, anterior limbic, SA and rostral part of cingulate (Cg) cortical areas were also labeled in most of our cases. (2) Ventral injections into the CN elicited a higher number of retrogradely labeled neurons in the ventral prefrontal area than dorsal injections. (3) A topographical relationship was found between the caudal CN and the dorsomedial prefrontal area so that dorsal injections in the caudal CN elicited retrograde labeling in the rostral PfDl, whereas ventral injections labeled the caudal PfDl. (4) A topography from dorsal to rostral and ventral to caudal was also observed between injections into the CN and PL and Cg. (5) A mediolateral topography was observed in the presylvian, cruciate and splenial sulci.

Chemical heterogeneity of the striosomal compartment in the human striatum.

The neurochemical organization of the striosomal compartment in the human striatum was analyzed by histochemical and immunohistochemical techniques applied to postmortem tissue from normal individuals. The striosomes were delineated by using the following markers: acetylcholinesterase (AChE), enkephalin (ENK), substance P (SP), calbindin-D28k (CB), parvalbumin (PV), calretinin (CR), limbic system-associated membrane protein (LAMP), choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), and NADPH-diaphorase. Comparisons were made between striosomal boundaries, as outlined by each marker applied on adjacent sections, and particular attention was paid to possible variations in the chemical features of striosomes along the rostrocaudal extent of the striatum. The main findings of this study are as follows: 1) the striosomal compartment is composed of two chemically distinct domains: a core and a peripheral region; 2) the core is largely devoid of CB and displays a less intense staining for ENK and LAMP than the peripheral region; 3) although striosomes are largely devoid of AChE, the activity of this enzyme is slightly higher in the core than in the peripheral region; 4) the core and peripheral regions are weakly stained for PV and intensely stained for SP; 5) ChAT-, CR- and NADPH-diaphorase-positive neurons are preferentially distributed in the peripheral region; 6) at rostral striatal levels, striosomes are largely devoid of TH, whereas the inverse is true caudally; and 7) at caudal striatal levels, the peripheral region of striosomes is intensely stained for CB and ChAT. These results demonstrate that the striosomes in human display a strikingly complex and heterogeneous chemical architecture.

Relationships between thalamostriatal neurons and pedunculopontine projections to the thalamus: a neuroanatomical tract-tracing study in the rat.

The present study aimed to investigate whether the pedunculopontine projection to the thalamus overlaps with identified thalamostriatal neurons. These projections were studied using a dual tract-tracing procedure combining anterogradely transported biotinylated dextran amine (pedunculopontine projections) and retrogradely transported Fluoro-Gold (thalamostriatal projections). Overlapping thalamic territories between thalamostriatal neurons and the axon terminals arising from the pedunculopontine tegmental nucleus were observed in the midline (paraventricular) and in the intralaminar (centrolateral, central medial, paracentral and parafascicular) thalamic nuclei. Other thalamic nuclei, such as the ethmoid, intermediodorsal, mediodorsal, paratenial, posteromedian, ventromedian, ventrolateral and rhomboid thalamic nuclei, displayed a lesser degree of overlap. These observations suggest the existence of presumptive contacts between thalamostriatal neurons and axons emerging from the pedunculopontine tegmental nucleus, therefore supporting the possible existence of feedback circuits in the rat basal ganglia in which the tegmento-thalamic projection would play a major role.

Thalamic interaction between the input and the output systems of the basal ganglia.

The striatal return through the thalamus is largely neglected in current studies dealing with basal ganglia function, and its role within this circuitry remains obscure. In this contribution the thalamus is regarded as an important place of interaction between the input and the output organization of the basal ganglia. In support of this idea, a brief overview is provided of some of the most recent findings concerning the thalamus in relation to the basal ganglia circuitry. In particular, we have focused on the thalamostriatal projections themselves, on the output of the basal ganglia to the thalamus and also on the overlapping territories between the thalamic projection of the output nuclei and the thalamostriatal neurons. These data support the existence of several thalamic feedback circuits within the basal ganglia neural system. Finally, some considerations are provided upon the functional significance of these thalamic feedback circuits in the overall organization of the basal ganglia.