Efferent projections of the infralimbic (area 25) region of the medial prefrontal cortex in the rat: an anterograde tracer PHA-L study

The efferent projections of the infralimbic region (IL) of the medial prefrontal cortex of the rat were examined by using the anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L). Major targets of the IL were found to include the agranular insular cortex, olfactory tubercle, perirhinal cortex, the whole amygdaloid complex, caudate putamen, accumbens nucleus, bed nucleus of the stria terminalis, midline thalamic nuclei, the lateral preoptic nucleus, paraventricular nucleus, supramammillary nucleus, medial mammillary nucleus, dorsal and posterior areas of the hypothalamus, ventral tegmental area, central gray, interpeduncular nucleus, dorsal raphe, lateral parabrachial nucleus and locus coeruleus. Previously unreported projections of the IL to the anterior olfactory nucleus, piriform cortex, anterior hypothalamic area and lateroanterior hypothalamic nucleus were observed. The density of labeled terminals was especially high in the agranular insular cortex, olfactory tubercle, medial division of the mediodorsal nucleus of the thalamus, dorsal hypothalamic area and the lateral division of the central amygdaloid nucleus. Several physiological and pharmacological studies have suggested that the IL functions as the 'visceral motor' cortex, involved in autonomic integration with behavioral and emotional events. The present investigation is the first comprehensive study of the IL efferent projections to support this concept.     

Efferent connections of the subthalamic region in the rat. II. The zona incerta

The efferent connections of the zona incerta (ZI) were studied experimentally in the rat by the aid of the autoradiographic tracer technique.Small microelectrophoretic injections of tritiated proline and leucine practically confined to the ZI were found to label a widespread, predominantly ipsilateral system of descending and ascending fibers distributed to reticular structures of the brain stem (mesencephalic reticular formation, nucleus tegmenti pedunculopontinus pars compacta, parabrachial area, nuclei reticularis pontis oralis, pontis caudalis, gigantocellularis and medullae oblongatae, pars ventralis), precerebellar nuclei (nucleus reticularis tegmenti pontis, pontine nuclei and inferior olivary complex), the middle and deep layers of the superior colliculus, the pretectum (anterior, posterior and medial pretectal nuclei), perioculomotor nuclei (interstitial nucleus of Cajal, nucleus of Darkschewitsch and nuclei of the posterior commissure), the parvocellular portion of the red nucleus, the central gray substance, the nucleus tegmenti dorsalis lateralis, the ventral horn of the cervical spinal cord, non-specific thalamic nuclei (parafascicular, centralis medius, paracentralis centralis lateralis and ventromedial thalamic nuclei, nucleus reuniens), basal ganglia (entopeduncular nucleus and globus pallidus), hypothalamic structures (posterior hypothalamic nucleus, dorsal and lateral hypothalamic areas), and a subpallidal district of the substantia innominata. Isotope injections centered in Forel's field H₁ resulted in the labeling of a similar set of projections. Some of the possible functional correlates of these connections are briefly discussed.     

Electrophysiology and pharmacology of neurons of the medial zona incerta: an in vitro slice study

The electrical properties and chemical sensitivities of neurons located in the medial zona incerta (ZI), a region containing a clustering of dopaminergic cell bodies known as the A13 cell group, were studied in Sprague-Dawley female rats in the in vitro slice preparation. Extracellular single cell recordings were made from 473 neurons located in the medial ZI. The neurons generally displayed a slow and regular firing pattern with a mean firing rate of 4.7 impulses/s. Some neurons exhibited an orthodromic response to electrical stimulation of the ventromedial nucleus of the hypothalamus (VMH). The response consisted of a short-term, variable-latency increase in activity, indicating a predominantly excitatory input from the VMH to the medial ZI. The chemical sensitivity of medial ZI neurons was tested by micropressure application of various neurotransmitters and peptides. Dopamine and serotonin were found to inhibit the spontaneous firing in many of the neurons tested, whereas none of the peptides tested consistently produced a short-term change in firing rate. Over half (51%) of the cells that were orthodromically excited by VMH stimulation were also inhibited by the exogenous application of dopamine. Since many of the cells in the medial ZI are dopaminergic and are believed to be autoregulated, the present findings indicate that a portion of the VMH neurons that project to the medial ZI may be synapsing on dopaminergic neurons.     

Light microscopic evidence of striatal input to intrapallidal neurons of cholinergic cell group Ch4 in the rat: a study employing the anterograde tracerPhaseolus vulgaris leucoagglutinin (PHA-L)

Injections of the anterograde tracerPhaseolus vulgaris leucoagglutinin (PHA-L) were placed in various striatal loci in the rat. Within the globus pallidus, PHA-L-filled striatofugal axons were seen to approach cholinergic neurons, identified with either acetylcholinesterase histochemistry or choline acetyltransferase immunohistochemistry, and, apparently, to contact the surface of such cells with axonal varicosities. Since these varicosities are thought to mark the sites of synaptic terminals, such juxtapositions provide strong light-microscopic evidence that intrapallidal cholinergic neurons in the rat receive a direct innervation from the striatum and are integrated into the circuitry of the basal ganglia.     

The peripheral and central projections of the Edinger-Westphal nucleus in the rat. A light and electron microscopic tracing study

The peripheral and central efferent projections of the rostral part of the Edinger-Westphal nucleus in the rat were investigated at the light and electron microscopic level by means of iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin and retrograde tracer injections of Fast blue and Nuclear yellow into the facial nucleus and into the principal olive. Two pathways leaving the rostral part of the Edinger-Westphal nucleus were studied, a peripheral and a central descending pathway. Fluorescent experiments demonstrated that the central pathway fibers originated from distinct individual Edinger-Westphal neurons. These neurons were mainly distributed throughout the rostral part of the Edinger-Westphal nucleus and had fusiform cell bodies. The neurons rarely form collateral projections. The central descending pathway left the Edinger-Westphal nucleus medially and terminated bilaterally in the principal olive, in the subnuclei A, B and C of the inferior olive and ipsilaterally in the medial accessory olive. The central pathway also terminated contralaterally in the lateral parabrachial nucleus, the facial nucleus, the trigeminal brainstem nuclear complex, the lateral reticular nucleus and the rostroventral reticular nucleus. The projection to the facial nucleus provides evidence for the existence of a polysynaptic loop forming the central part of the corneal blink reflex. Projections from the Edinger-Westphal nucleus to the cerebellar cortex or the deep nuclei, as described in cat and primate, could not be confirmed. The peripheral pathway left the Edinger-Westphal nucleus ventrally and terminated on dendrites of ciliary ganglion cells, along smooth muscle cells of ciliary ganglion associated arterioles and in the proximity of ciliary ganglion associated venules. The central and peripheral terminals that originate in the Edinger-Westphal nucleus all had similar ultrastructural features: clear, round vesicles and electron dense mitochondria. The terminals originating from the central descending pathway were often found to be arranged in glomerular-like structures. The central and peripheral terminals made asymmetric synaptic membrane specializations (Gray type one), except terminals innervating the ciliary ganglion associated vessels, which showed no synaptic contacts.     

A direct neuronal projection from the entopeduncular nucleus to the globus pallidus. A PHA-L anterograde tracing study in the rat

The efferent projections of the rat entopeduncular nucleus were examined by use of the anterogradely transported lectin Phaseolus vulgaris-leucoagglutinin (PHA-L). Injections of PHA-L into different parts of the entopeduncular nucleus resulted in a moderate number of labeled nerve fibers in the ipsilateral globus pallidus. The fibers displayed a heterogeneous morphology: some were of small caliber with few delicate varicosities, others were of medium caliber with several more bulbous nerve terminals. Restricted injections in the dorsal and ventral parts of the entopeduncular nucleus, respectively, showed that the dorsal part of the entopeduncular nucleus projects to the dorsal and rostral parts of the dorsal pallidum and the ventral part to the ventral and caudal parts.     

Efferent connections from the anterior pretectal nucleus to the diencephalon and mesencephalon in the rat

The anterior pretectal nucleus has been described as part of the visual pretectal complex. However, several electrophysiological and behavioural studies showed that this area is involved in somatosensory modulation, more specifically, antinociception. The efferents of the anterior pretectal nucleus have not been identified taking into account the different function of this nucleus in relation to the rest of the pretectal complex. In the study herein described, a sensitive anterograde tracer Phaseolus vulgaris leucoagglutinin was used to trace the mesencephalic and diencephalic efferents of the anterior pretectal nucleus in the rat. The majority of the connections were ipsilateral. Fibres with varicosities were observed in discrete areas of the thalamus (central lateral, posterior complex), hypothalamus (lateral, posterior and ventromedial), zona incerta, parvocellular red nucleus, intermediate and deep layers of the superior colliculus, central grey, deep mesencephalon, pontine parabrachial region, and pontine nuclei. Fibres en passant were detected in the medial lemniscus, from the level of the injection site to rostral medullary levels. Some labelled axons were seen coursing to the contralateral side through the posterior commissure and the decussation of the superior cerebellar peduncle. These results show that the anterior pretectal nucleus projects principally to areas involved in somatosensory and motor control in a manner that permits sensory modulation at higher and lower levels of the brain. These connections may explain the antinociceptive and antiaversive effects of stimulating the anterior pretectal nucleus in freely moving animals.     

Efferent projections from posteroventral cochlear nucleus to lateral superior olive in guinea pig

Phaseolus vulgaris leucoagglutinin (PHA-L), a kidney bean lectin used as an anterograde tracer, was iontophoretically injected into the posteroventral cochlear nucleus (PVCN) of guinea pigs. PHA-L-labeled fiber segments and their terminal specializations were observed within the ipsilateral lateral superior olive (LSO) thereby establishing the existence of an efferent neural pathway from PVCN to this nucleus. Furthermore, the pathway is topographically organized with dorsal regions of PVCN projecting to the medial limb and ventral regions projecting to the lateral limb of LSO.     

The efferent connections of the pupillary constriction area in the rat medial frontal cortex

This study investigated, in the rat, the efferent projections of the pupillary constriction area, which is located within the medial frontal cortex. In order to identify the location of the pupillary constriction area, in preliminary experiments the medial frontal cortex was microstimulated. Intracortical microstimulation elicited pupillary constriction in a thin strip of cortex near the interhemispheric fissure and bordering the frontal eye field and vibrissae area of the somatomotor cortex. Seven animals received a single iontophoretic injection of Phaseolus vulgaris leucoagglutinin in the pupillary constriction area. In these cases, anterogradely labelled fibres and terminal-like elements were found in both hemispheres. The densest labeling was seen in several areas of the injected hemisphere, where labeled fibers prevailed in the secondary visual cortex. Dense labeled fibers were also found in the retrosplenial and cingulate cortex. In the thalamus, labeled fibers were seen in the intralaminar nuclei and posterior nuclear group. In the midbrain and pons, labeled fibers were located in the anterior pretectal area, superior colliculus and in the dorsolateral portion of the central gray. Contralaterally to the injection site, labeled fibers were distributed in the homotopic region. These findings led us to assume that, in the medial frontal cortex of the rat, besides controlling pupillary constriction, the pupillary constriction area may also be involved in controlling orientation and exploring behavior.     

Efferent projections of the subthalamic nucleus in the rat: light and electron microscopic analysis with the PHA-L method

Efferent projections of rat subthalamic nucleus were studied by use of the axonal transport of phaseolus vulgaris-leucoagglutinin (PHA-L), and the results were analyzed with light and electron microscopes. PHA-L injections in the subthalamic nucleus (STH) resulted in heavy labeling of fiber plexus with en passant boutons and terminals in the pallidal complex, i.e., the entopeduncular nucleus (EP), the globus pallidus (GP) and the ventral pallidum (VP), and the substantia nigra pars reticulata (SNR). Labeling in GP was characterized by two distinct bands of labeled terminals oriented dorsoventrally, whereas labeling in SNR was patchy. STH efferents to the pallidum and SNR displayed a mediolateral topographic organization. With regard to dorsoventral organization, projections to GP were inverted, but those to SNR were not. There were moderate projections to the neostriatum and sparse projections to the frontal cortex, substantia innominata, substantia nigra pars compacta (SNC), pedunculopontine tegmental nucleus, ventral part of the central gray matter including the dorsal raphe nucleus, and the mesencephalic and pontine reticular formation. PHA-L injections in the zona incerta and the lateral hypothalamic area resulted in fiber and terminal labelings in many structures, including the basal forebrain, EP, SNC, and other brainstem areas that overlap with some of the terminal sites of STH projections. Ultrastructural observations of PHA-L labeled processes in GP and SNR revealed that STH terminals in both structures contained small pleomorphic vesicles and formed asymmetrical contacts. These contacts were mainly on dendritic shafts, but some were on somata. It also was observed that the myelinated axons of STH neurons lost their myelin after reaching their target areas and the synaptic boutons arose from relatively thin unmyelinated axons.     

Associational projections of the anterior midline cortex in the rat: intracingulate and retrosplenial connections

Past studies indicate that distinct areas of anterior midline cortex in the rat contribute to diverse functions, such as autonomic nervous system regulation and learning, but the anatomical substrate for these functions has not been fully elucidated. The present study characterizes the associational connections within the midline cortex of the rat by using the anterograde transport of Phaseolus vulgaris leucoagglutinin and Fluororuby. The prelimbic area and the rostral part of the anterior cingulate area (both dorsal and ventral subdivisions) are extensively interconnected with each other. In addition, the caudal half of anterior cingulate cortex has extensive projections to precentral medial cortex and caudally directed projections to retrosplenial cortex. Other cortical areas within anterior midline cortex have relatively limited cortical–cortical projections. The infralimbic, dorsal peduncular, and medial precentral cortices have dense intrinsic projections, but have either very limited or no projections to other areas in the anterior midline cortex. Although it has been suggested that cortical–cortical projections from anterior cingulate cortex and prelimbic cortex to infralimbic cortex may be important for linking learning processes with an autonomic nervous system response, the paucity of direct projections between these areas calls this hypothesis into question. Conversely, the results suggest that the anterior midline cortex contains two regions that are functionally and connectionally distinct.     

Melanin-concentrating hormone and neuropeptide EI projections from the lateral hypothalamic area and zona incerta to the medial septal nucleus and spinal cord: a study using multiple neuronal tracers

The projection pathways of neurons containing melanin-concentrating hormone (MCH) and neuropeptide EI (NEI), two peptides colocalized in the lateral hypothalamic area (LHA) of the rat, were mapped using the retrogradely transported fluorescent dyes, true blue (TB) and diamidino yellow (DY). TB and DY were injected into the medial septum/diagonal band complex (MS/DBC) and the thoracic level of the spinal cord (SpCd), respectively. Brains from rats receiving only one or both tracer injections were immunohistochemically stained for MCH in the spinal cord and NEI in the forebrain. In the MS/DBC, NEI-immunoreactive (-ir) fibers are concentrated in the MS and in the vertical and horizontal limbs of the DBC. In the SpCd, MCH-ir fibers are concentrated primarily in lamina X. Of the diencephalic NEI-ir neurons, 37.15% project to the MS/DBC and reside in the rostromedial zona incerta (ZIm), in the LHA_t and LHA_p, and in the perifornical region. Of the diencephalic MCH-ir neurons, 20.2% project to the SpCd and reside in the LHA_t and LHA_p. In addition, 2.2% of the MCH-ir cells and 8.7% of the NEI-ir cells in the hypothalamus were labeled with both retrograde tracers and thus project to both the MS/DBC and SpCd. These dual projection neurons are located mainly in the LHA_t and LHA_p. Anterograde injections of the tracer Phaseolus vulgaris leucoagglutinin into the LHA_t and ZIm corroborated our findings in the retrograde studies. Potential autonomic and behavioral roles of the NEI and MCH systems in the MS/DBC and the SpCd are discussed.     

Cortical projection patterns of magnocellular basal nucleus subdivisions as revealed by anterogradely transportedPhaseolus vulgaris leucoagglutinin

The present paper deals with a detailed analysis of cortical projections from the magnocellular basal nucleus (MBN) and horizontal limb of the diagonal band of Broca (HDB) in the rat. The MBN and HDB were injected iontophoretically with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). After immunocytochemical visualization of labeled efferents, the distribution of projections over the cortical mantle, olfactory regions and amygdala were studied by light microscopy. Based on differences in cortical projection patterns, the MBN was subdivided in anterior, intermediate and posterior portions (MBNa, MBNi and MBNp). All subdivisions maintain neocortical projections and are subject to an anterior to posterior topographic arrangement. In the overall pattern, however, the frontal cortex is the chief target. Furthermore, all MBN parts project to various regions of meso- and allocortex, which are progressively more dense when the tracer injection is more anteriorly placed. The most conspicuous finding, however, was a ventrolateral to dorsomedial cortical projection pattern as the PHA-L injection site moved from posterior to anterior. Thus, the posterior MBN projects predominantly to lateral neo- and mesocortex while the anterior MBN sends more fibers to the medial cortical regions. Furthermore, the MBNa is a source of considerable afferent input to the olfactory nuclei and as such should be regarded as a transition to the HDB. The HDB, apart from projecting densely to olfactory bulb and related nuclei, maintains a substantial output to the medial prefrontal cortical regions and entorhinal cortex, as well. Comparison of young vs aged cases indicate that aging does not appear to have a profound influence on cortical innervation patterns, at least as studied with the PHA-L method.     

Parvalbumin-containing neurons in the basal forebrain receive direct input from the substantia nigra-ventral tegmental area

By means of anterograde tracing of Phaseolus vulgaris-leucoagglutinin (PHA-L) it was determined if parvalbumin-immunoreactive neurons in the basal forebrain receive a direct synaptic input from the A9–A10 dopaminergic nuclei of the substantia nigra and ventral tegmental area. Forebrain sections were processed for immunocytochemical detection of PHA-L and parvalbumin (PV) at light and electron microscopic levels. At the ultrastructural level, PHA-L-labeled terminals were found to establish synaptic contacts with PV-immunoreactive neuronal somata in the ventromedial globus pallidus, the ventral pallidum, the internal capsule, and the substantia innominata. PV-containing neurons in pallidal and adjacent basal forebrain territories are thus directly targeted by presumably A9–A10 dopaminergic neurons and represent a novel aspect of midbrain dopaminergic control of basal forebrain neuronal activity.     

Neurochemical identification of A13 dopaminergic neuronal projections from the medial zona incerta to the horizontal limb of the diagonal band of Broca and the central nucleus of the amygdala

Studies utilizing fluorescent histochemical techniques first revealed that A₁₃ dopaminergic (DA) perikarya located in medial zona incerta (MZI) project to various regions within the hypothalamus; accordingly, these DA neurons were designated the ‘incertohypothalamic’ DA neuronal system. More recently, it has been shown that the anterograde neuronal tract tracer Phaseolus vulgaris leucoagglutinin, after injection into MZI, is identified in nerve terminals outside of the hypothalamus: for example, in horizontal limb of the diagonal band of Broca (HDB) and central nucleus of the amygdala (cAMY). The purpose of the present study was to determine, using neurochemical techniques, if A₁₃ DA neurons project to the HDB and cAMY. Concentrations of dopamine and one of its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) were determined in HDB and cAMY following: (1) electrical stimulation of MZI, (2) electrolytic lesion or knife ablation of MZI, and (3) administration of gamma-hydroxybutyric acid (GHBA) into MZI. For comparison, similar measurements were made in nucleus accumbens (N. Acc.), a terminal region of A₁₀ DA neurons in the ventral tegmental area (VTA). Electrical stimulation of MZI increased DOPAC concentrations in HDB and cAMY, whereas electrolytic or ablative lesions of MZI decreased dopamine concentrations in both of these regions. By contrast, neither stimulation nor lesion of MZI had any effect on DOPAC or dopamine concentrations in N. Acc. Intracerebral injection of GHBA into MZI increased dopamine concentrations in MZI and HDB, but not in cAMY or N. Acc. Intracerebral administration of GHBA into VTA increased dopamine concentrations in HDB and N. Acc., but not in MZI or cAMY. These results suggest that A₁₃ DA neurons project to HDB and cAMY but not to N. Acc., and HDB receives projections from both A₁₀ and A₁₃ DA neurons.     

The projection from the parataenial thalamic nucleus, as demonstrated by the Phaseolus vulgaris-leucoagglutinin (PHA-L) method, identifies a subterritorial organization of the ventral striatum

The thalamic projection to the ventral striatum was examined in the rat by immunohistochemistry after iontophoretic injections ofPhaseolus vulgaris-leucoagglutinin (PHA-L) into the parataenial thalamic nucleus. A continuous dense terminal field was observed in the nucleus accumbens and the striatal cell bridges, as well as in the adjoining striatal parts of the olfactory tubercle. These observations provide further evidence of the relevance of the ventral striatal concept.     

Convergence of subthalamic and striatal efferents at pallidal level in primates: an anterograde double-labeling study with biocytin and PHA-L

Small injections of two highly sensitive anterograde tracers, Phaseolus vulgaris-leucoagglutinin (PHA-L) and biocytin, into the striatum and the subthalamic nucleus of squirrel monkeys (Saimiri sciureus) have revealed a high degree of convergence of striatal and subthalamic fibers upon single pallidal cells. Both afferent systems formed highly complex band-like patterns that were largely in register with one another. At single cell level, the somata of pallidal neurons were closely surrounded by subthalamic terminal varicosities, whereas the dendrites were entwined mostly by striatal fibers. Typically, a subthalamopallidal fiber coursed in a caudorostral direction and arborized according to a uniform pattern along its trajectory in the pallidum. Numerous thin and markedly varicose axon collaterals detached themselves at right angle from the main subthalamopallidal fiber. These highly branched collaterals were mostly oriented along the mediolateral plane and entwined rather loosely the dendrites but surrounded very closely the somata of pallidal neurons. In contrast, a striatopallidal fiber travelled in a rostrocaudal direction. Its initial segment made only en passant contacts with pallidal cell bodies, whereas its distal end closely entwined the dendrites of pallidal neurons, forming arrangements similar to 'woolly' type fibers. These results suggest that a single subthalamic fiber may influence a rather large collection of pallidal neurons in a similar fashion, compared to the striatal input which appears to exert a more specific control upon selected sets of the same pallidal neurons.     

Neuroanatomical tracing by use of Phaseolus vulgaris-leucoagglutinin (PHA-L): electron microscopy of PHA-L-filled neuronal somata, dendrites, axons and axon terminals

Following iotophoretic application of the plant lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) to brain areas of rats, and subsequent immunohistochemistry, reaction product can be observed with the light microscope to fill neurons completely, including their somata, dendrites, dendritic appendages and axons. Moreover, axons often show profuse collateralization and indications of termination, including numerous en passant and terminal varicosities. The present report describes a protocol for combining light microscopic examination of PHA-L-stained neurons and electron microscopy of details of their processes, including the axonal varicosities. The results support the hypothesis that axonal varicosities are the light microscopic representations of synaptic axon terminals seen in electron microscopic preparations.     

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.     

The striatopallidal projection displays a high degree of anatomical specificity in the primate

The striatopallidal projection in the squirrel monkey (Saimiri sciureus) was studied with two highly sensitive anterograde tracers, the lectin Phaseolus vulgaris leucoagglutinin (PHA-L) and biocytin. After small PHA-L injections into various sectors of the striatum, the striatopallidal projection was found to display a very precise topographical organization. Fibers from the head of the caudate nucleus emerge as several distinct fascicles that penetrate the dorsal portion of the pallidum at various points along its rostrocaudal extent. Each fascicle arborizes into the dorsal third of the pallidum as dense plexuses composed of numerous fibers that closely entwined the dendrites of pallidal neurons, hence forming typical 'woolly' fiber arrangements. In contrast, fibers from the postcommissural putamen emerge as a few compact bundles that reach the pallidum through its lateral surface. In the pallidum, thin fibers detach themselves from these compact bundles, sweep caudally, and arborize in the form of narrow and elongated bands aligned parallel to the medullary laminae. Each band appears composed of numerous, thin and weakly varicose fibers that make only en passant type of contact with pallidal cell bodies rostrally, but form a dense field of woolly fibers caudally. In cases in which two PHA-L injections were made at two different rostrocaudal levels in the putamen, two rostrocaudally distant fields of woolly fibers, separated one another by thin varicose fibers, occur in each band. Furthermore, each PHA-L injection site in the striatum gives rise to at least two bands in each pallidal segment, indicating that the primate striatum has a dual representation at pallidal level. Finally, injections of PHA-L and biocytin into two small and mediolaterally adjacent areas of the postcommissural putamen lead to the formation of two clearly distinguishable sets of bands in each pallidal segment. Even though they lie very close to one another these two types of bands never really overlap. This experiment shows that, in contrast to previous beliefs, axons of striatal neurons from two small adjacent populations do not converge upon the same pallidal neurons but instead project to several distinct subsets of pallidal neurons. The findings of the present study reveal that the striatopallidal projection system in primates is highly ordered and displays a high degree of specificity with respect to its target sites in the pallidum. Different anatomical strategies are used to maximally exploit the relatively small pallidal space and ensure that the finely tuned corticostriatal information is not blurred as it flows through the funnel-shaped pallidum.