Distributed but convergent ordering of corticostriatal projections: analysis of the frontal eye field and the supplementary eye field in the macaque monkey.

The degree of parallel processing in frontal cortex-basal ganglia circuits is a central and debated issue in research on the basal ganglia. To approach this issue directly, we analyzed and compared the corticostriatal projections of two principal oculomotor areas of the frontal lobes, the frontal eye field (FEF) and the supplementary eye field (SEF). We first identified cortical regions within or adjacent to each eye field by microstimulation in macaque monkeys and then injected each site with either 35S-methionine or WGA-HRP conjugate. We analyzed the corticostriatal projections and also the interconnections of the pairs of cortical areas. We observed major convergence of the projections of the FEF and the SEF within the striatum, principally in the caudate nucleus. In cross sections through the striatum, both projections were broken into a series of discontinuous input zones that seemed to be part of complex three-dimensional labyrinths. Where the FEF and SEF projection fields were both present, they overlapped patch for patch. Thus, both inputs were dispersed within the striatum but converged with one another. Striatal afferents from cortex adjacent to the FEF and the SEF did not show convergence with SEF and FEF inputs, but did, in part, converge with one another. For all pairs of cortical areas tested, the degree of overlap in the corticostriatal projections appeared to be directly correlated with the degree of cortical interconnectivity of the areas injected. All of the corticostriatal fiber projections observed primarily avoided immunohistochemically identified striosomes. We conclude that there is convergence of oculomotor information from two distinct regions of the frontal cortex to the striatal matrix, which is known to project into pallidonigral circuits including the striatonigrocollicular pathway of the saccadic eye movement system. Furthermore, functionally distinct premotor areas near the oculomotor fields often systematically projected to striatal zones adjacent to oculomotor field projections, suggesting an anatomical basis for potential interaction of these inputs within the striatum. We propose that parallel processing is not the exclusive principle of organization of forebrain circuits associated with the basal ganglia. Rather, patterns of both convergence and divergence are present and are likely to depend on multiple functional and developmental constraints.     

Differential synaptology of vGluT2-containing thalamostriatal afferents between the patch and matrix compartments in rats

The striatum is divided into two compartments named the patch (or striosome) and the matrix. Although these two compartments can be differentiated by their neurochemical content or afferent and efferent projections, the synaptology of inputs to these striatal regions remains poorly characterized. By using the vesicular glutamate transporters vGluT1 and vGluT2, as markers of corticostriatal and thalamostriatal projections, respectively, we demonstrate a differential pattern of synaptic connections of these two pathways between the patch and the matrix compartments. We also demonstrate that the majority of vGluT2-immunolabeled axon terminals form axospinous synapses, suggesting that thalamic afferents, like corticostriatal inputs, terminate preferentially onto spines in the striatum. Within both compartments, more than 90% of vGluT1-containing terminals formed axospinous synapses, whereas 87% of vGluT2-positive terminals within the patch innervated dendritic spines, but only 55% did so in the matrix. To characterize further the source of thalamic inputs that could account for the increase in axodendritic synapses in the matrix, we undertook an electron microscopic analysis of the synaptology of thalamostriatal afferents to the matrix compartments from specific intralaminar, midline, relay, and associative thalamic nuclei in rats. Approximately 95% of PHA-L-labeled terminals from the central lateral, midline, mediodorsal, lateral dorsal, anteroventral, and ventral anterior/ventral lateral nuclei formed axospinous synapses, a pattern reminiscent of corticostriatal afferents but strikingly different from thalamostriatal projections arising from the parafascicular nucleus (PF), which terminated onto dendritic shafts. These findings provide the first evidence for a differential pattern of synaptic organization of thalamostriatal glutamatergic inputs to the patch and matrix compartments. Furthermore, they demonstrate that the PF is the sole source of significant axodendritic thalamic inputs to striatal projection neurons. These observations pave the way for understanding differential regulatory mechanisms of striatal outflow from the patch and matrix compartments by thalamostriatal afferents.     

Role of corticostriatal and nigrostriatal inputs in malonate-induced striatal toxicity

The striatal neuronal loss evident following cellular metabolic compromise may be dependent upon the presence of glutamate and dopamine within the striatum. In order to investigate the relative roles of corticostriatal and nigrostriatal projections in malonate-induced neuronal loss, the extent of toxicity was quantified in animals with cortical lesions to deplete the striatum of glutamate, nigrostriatal lesions to deplete the striatum of dopamine, or both. We found that malonate-induced striatal toxicity was significantly reduced following lesions of either the glutamatergic or dopaminergic afferents to the striatum. The extent of attenuation following the loss of both inputs within the same animal was similar to that seen following lesions of either alone. These data suggest that malonate-induced toxicity in the striatum depends upon the integrity of interactive influences from both glutamatergic and dopaminergic afferents.     

Laminar Origin of Corticostriatal Projections to the Motor Putamen in the Macaque Brain

In the macaque brain, projections from distant, interconnected cortical areas converge in specific zones of the striatum. For example, specific zones of the motor putamen are targets of projections from frontal motor, inferior parietal, and ventrolateral prefrontal hand-related areas and thus are integral part of the so-called “lateral grasping network.” In the present study, we analyzed the laminar distribution of corticostriatal neurons projecting to different parts of the motor putamen. Retrograde neural tracers were injected in different parts of the putamen in 3 Macaca mulatta (one male) and the laminar distribution of the labeled corticostriatal neurons was analyzed quantitatively. In frontal motor areas and frontal operculum, where most labeled cells were located, almost everywhere the proportion of corticostriatal labeled neurons in layers III and/or VI was comparable or even stronger than in layer V. Furthermore, within these regions, the laminar distribution pattern of corticostriatal labeled neurons largely varied independently from their density and from the projecting area/sector, but likely according to the target striatal zone. Accordingly, the present data show that cortical areas may project in different ways to different striatal zones, which can be targets of specific combinations of signals originating from the various cortical layers of the areas of a given network. These observations extend current models of corticostriatal interactions, suggesting more complex modes of information processing in the basal ganglia for different motor and nonmotor functions and opening new questions on the architecture of the corticostriatal circuitry.SIGNIFICANCE STATEMENT Projections from the ipsilateral cerebral cortex are the major source of input to the striatum. Previous studies have provided evidence for distinct zones of the putamen specified by converging projections from specific sets of interconnected cortical areas. The present study shows that the distribution of corticostriatal neurons in the various layers of the primary motor and premotor areas varies depending on the target striatal zone. Accordingly, different striatal zones collect specific combinations of signals from the various cortical layers of their input areas, possibly differing in terms of coding, timing, and direction of information flow (e.g., feed-forward, or feed-back).     

Primate striatonigral projections: A comparison of the sensorimotor-related striatum and the ventral striatum

The striatum receives topographic cortical inputs with the limbic lobe terminating in the ventral striatum and sensorimotor cortical regions terminating in the dorsolateral striatum. The organization of striatonigral projections originating from these different striatal territories was examined in primate by using several anterograde tracers. The ventral striatum innervates a large area of the substantia nigra, including the medial pars reticulata and much of the pars compacta. Moreover, projections from separate areas of the ventral striatum overlap considerably in the substantia nigra. No mediolateral or rostrocaudal topographic order is apparent, and the area of the substantia nigra associated with the ventral striatum is extensive. In contrast, the sensorimotor-related striatum innervates a limited region of the ventrolateral substantia nigra. Similar to ventral striatonigral projections, projections originating from different areas of the sensorimotor-related striatum send converging inputs to the substantia nigra. Sensorimotor-related striatonigral projections avoid the region of the dopaminergic neurons in the dorsal pars compacta. Striatonigral projections from the sensorimotor-related and ventral striatum do not overlap in the substantia nigra. Examination of the outputs of discrete striatal loci indicates that the organization of striatonigral projections is more related to corticostriatal inputs than to a simple rostrocaudal, dorsoventral, or mediolateral tpography of the striatum. Striatal projections that originate from different striatal territories are distinct and nonoverlapping, thus supporting the concept of segregated striatonigral circuits. However, areas of the striatum that receive common cortical inputs send converging inputs to the substantia nigra. This suggests that the substantia nigra is also an important link for integrating information between functionally related (sub)circuits. © 1994 Wiley-Liss, Inc.     

Neostriatal projections from individual cortical fields conform to histochemically distinct striatal compartments in the rat

A number of recent studies have demonstrated two chemically distinct compartments in the neostriatum: opiate receptor-rich patches and a surrounding matrix. Using axonal transport and receptor localization techniques in the rat brain, we have found that striatal projections from architectonically distinct cortical fields conform to this compartmentalized plan. The prelimbic cortex has bilateral projections that concentrate within the striatal patches. In contrast, the agranular motor cortex and cingulate cortex have bilateral projections to the matrix, while the somatic sensory cortex and visual cortex have ipsilateral matrix projections. Each matrix input occupies a characteristic striatal district. The projection to the patches distributes prelimbic input throughout the striatum, which may allow for prelimbic interactions with input from all other cortical areas.     

Synaptic convergence of motor and somatosensory cortical afferents onto GABAergic interneurons in the rat striatum

Cortical afferents to the basal ganglia, and in particular the corticostriatal projections, are critical in the expression of basal ganglia function in health and disease. The corticostriatal projections are topographically organized but also partially overlap and interdigitate. To determine whether projections from distinct cortical areas converge at the level of single interneurons in the striatum, double anterograde labeling from the primary motor (M1) and primary somatosensory (S1) cortices in the rat, was combined with immunolabeling for parvalbumin (PV), to identify one population of striatal GABAergic interneurons. Cortical afferents from M1 and S1 gave rise to distinct, but partially overlapping, arbors of varicose axons in the striatum. PV-positive neurons were often apposed by cortical terminals and, in many instances, apposed by terminals from both cortical areas. Frequently, individual cortical axons formed multiple varicosities apposed to the same PV-positive neuron. Electron microscopy confirmed that the cortical terminals formed asymmetric synapses with the dendrites and perikarya of PV-positive neurons as well as unlabelled dendritic spines. Correlated light and electron microscopy revealed that individual PV-positive neurons received synaptic input from axon terminals derived from both motor and somatosensory cortices. These results demonstrate that, within areas of overlap of functionally distinct projections, there is synaptic convergence at the single cell level. Sensorimotor integration in the basal ganglia is thus likely to be mediated, at least in part, by striatal GABAergic interneurons. Furthermore, our findings suggest that the pattern of innervation of GABAergic interneurons by cortical afferents is different from the cortical innervation of spiny projection neurons.     

Pattern of corticostriatal innervation in organotypic cocultures is dependent on the age of the cortical tissue

The patch-matrix organization of the striatum is defined by the selective expression of neuronal markers and a semisegregated pattern of afferents and efferents that develops before birth in all mammals. Differential projections from 'limbic' and 'somatomotor' cortices contribute to the selective circuitry of patch ("striosome") and matrix compartments. Organotypic cultures were used to determine the pattern of early corticostriatal innervation as a first step toward understanding the role of cortical innervation in the development of striatal patch-matrix organization. Perinatal striatum (E19-P4) was cocultured with the cortex obtained from same-age or different-age rats in the presence or absence of substantia nigra obtained from E14-15 fetuses. After 4-21 days in vitro, crystals of biocytin were placed directly onto the cortical piece to trace cortical projections into the striatal piece. Cortex obtained from fetuses (E19-22) or neonatal (P0-1) rats gave rise to a dense innervation of both prenatal and postnatal striatal slices; however, the pattern of biocytin-labeled fibers was found to be highly dependent on the age of the cortical tissue used. Cortex derived from rats between E20 and P1 gave rise to a heterogeneous distribution of fibers indicative of striatal patches when combined with striatal slices from same-age or younger (E18-19) fetuses. Cortex from E18-19 fetuses produced a homogeneous innervation even when cocultured with older striatal tissue in which the striatal patches were already present. The postnatal cortex (P2-P5) gave rise to little to no innervation of striatum of all ages. Similar findings were obtained with the use of either prelimbic or somatosensory cortex. In double- and triple-labeled cultures, the distribution of corticostriatal fibers overlapped substantially with patches of developing striatal neurons, as revealed by DARPP-32 immunocytochemistry. Dopaminergic innervation present when the substantia nigra was included in the cocultures also distributed preferentially to the developing patch compartment, but it did not substantially alter the pattern of corticostriatal innervation. These findings suggest that the cortex provides directive signals to the developing striatum rather than simply responding to the presence of patches that have already formed.     

Dendritic domains of medium spiny neurons in the primate striatum: Relationships to striosomal borders

Medium spiny neurons are the projection neurons of the striatum. They receive the majority of striatal afferents, and they make up the vast majority of all neurons in the striatum. These densely spiny cells thus constitute a major substrate for input-output processing in the striatum. In the experiments described here we analyzed the dendritic fields of spiny neurons in the squirrel monkey striatum and plotted their orientations with respect to the borders between striosomes and matrix. Medium-sized spiny neurons in the caudate nucleus were filled intracellularly in a fixed-slice preparation with the fluorescent dye Lucifer Yellow. Dendritic arbors were reconstructed following immunostaining of the injected neurons with antiserum to Lucifer Yellow and counterstaining for striosome/matrix compartments. A majority of the medium spiny neurons studied had dendritic arborizations that remained within their compartment of origin. Thus the striosome/matrix subdivision not only partitions neurotransmitter molecules and extrinsic striatal connections into two domains in the primate caudate nucleus, but also constrains the dendritic arbors of many projection neurons there. Other medium spiny neurons, however, in both striosomes and matrix, had dendrites that crossed from one compartment into the other. About a quarter of the spiny neurons reconstructed had at least one such crossing dendrite. These results suggest that compartmentalization of afferent and efferent processing by projection neurons in the primate striatum is not absolute. For a subpopulation of spiny neurons in striosomes and matrix, inputs to one compartment could have a direct influence on output cells of the other. © 1993 Wiley-Liss,Inc.     

Connections of the bullfrog striatum: afferent organization

Afferents to the dorsal and ventral striatum of the bullfrog (Rana catesbeiana) were revealed by horseradish peroxidase (HRP) histochemistry. Anterograde tracing techniques (autoradiography and anterograde HRP transport) were then used to confirm the projections and to describe their terminal fields within the striatum. The major input arises from the ipsilateral lateral anterior and central thalamic nuclei, which receive tectal (Rubinson, '68) and toral (Neary, '74) input, respectively. These projections terminate in a dense, homogeneous field within the striatal neuropil adjacent to the cell plates of both striatal divisions. A second heavy input arises from the anterior entopeduncular nucleus bilaterally, with axons from the contralateral side crossing in the anterior commissure. This input terminates in both striatal divisions but is heaviest ventrally. Sparser inputs are present from the ipsilateral lateral and medial amygdalar nuclei, the preoptic area (mainly from the very caudal suprachiasmatic division), the posterior tuberculum, and the ipsilateral superficial isthmal reticular nucleus of the tegmentum. All these afferents, with the possible exception of the preoptic input, ascend to the striatum via the lateral forebrain bundle, and all innervate both striatal divisions. The preoptic input terminates within the cell plates, as well as subpially in a pattern similar to that described for tubercular input (Neary and Wilczynski, '77). The tegmental input is very sparse and is most apparent superficially. Afferents from pallial telencephalic areas are not present, suggesting that although anurans receive striatal input from the diencephalon and mesencephalon, they do not possess a homolog of the mammalian corticostriatal system. Further, the extremely heavy input from the middle dorsal thalamic zone suggests that a major function of the anuran striatum involves processing sensory information from the midbrain roof.     

Morphology and compartmental location of cells exhibiting DNA damage after quinolinic acid injections into rat striatum.

Although excitotoxic injury is thought to play a role in many pathologic conditions, the type of cell death induced by excitotoxins in vivo and the basis for the differential vulnerability of neurons to excitotoxic injury are still poorly understood. Morphologic alterations and the presence of DNA damage were examined in adult rat striatum after an intrastriatal injection of low doses of quinolinic acid, a N-methyl-D-aspartate receptor agonist. Rats were killed 6, 8, 10, or 12 hours after quinolinate or vehicle injection. Numerous neurons with necrotic morphologies were detected in the quinolinate-injected striata. In addition, few neurons with apoptotic morphologies were found in the dorsomedial striatum. DNA strand breaks were detected in tissue sections by in situ nick translation with (35)S-radiolabeled nucleotides and emulsion autoradiography. Labeled cells were first detected outside the needle track 10 hours after quinolinate injection and, on average, 20% of neurons exhibited DNA damage by 12 hours after surgery. DNA damage was found in cells with both apoptotic and necrotic morphologies. A marked differential vulnerability to DNA damage at this time was observed in two striatal compartments, the striosomes, identified as regions of dense [(3)H]naloxone binding, and the extrastriosomal matrix: the great majority of labeled cells were found in the extrastriosomal matrix and extremely few were seen in the striosomes. This preferential distribution was not due to premature cell death in the striosomes which contained numerous unlabeled neurons. The results suggest a greater vulnerability of neurons in the matrix, versus the striosomes, to early excitotoxin-induced DNA damage in rat striatum.     

Compartmental organization of the thalamostriatal connection in the cat.

The compartmental organization of the thalamostriatal connection in the cat was studied by labelling thalamic fibers in anterograde axonal transport experiments and comparing their striatal distributions with the arrangement of striosomes and matrix tissue identified by histochemical staining methods. When analyzed according to their principal compartmental targets in dorsal striatum, the thalamic deposits indicated the existence of medial and lateral divisions within the thalamostriatal projection. Nuclei of the medial division, which includes parts of the thalamic midline, projected primarily to striosomes. The lateral division, which embraces the anterior and posterior intralaminar groups, the rostral ventral tier nuclei, and parts of the posterior lateral nuclear complex, predominantly innervated matrix tissue. In the dorsal division of the nucleus accumbens, the medial system preferentially terminated in zones that stain heavily in butyrylcholinesterase and substance P preparations, but fibers from both the medial and the lateral systems largely avoided the histochemically marked compartments such as the border islands of the nucleus accumbens that are seen elsewhere in the ventral striatum. Medial division: Thalamic deposits involving the paraventricular and rhomboid nuclei of the thalamic midline elicited labelling of striosomes and, invariably, ventral extrastriosomal matrix, the nucleus accumbens, and the amygdala. This projection was topographically organized: rostral thalamic deposits elicited labelling in the medial caudate nucleus and the medial nucleus accumbens. More caudal injections produced more lateral labelling. Lateral division: The lateral division is composed of at least three projection systems distinguished by their patterns of matrix innervation. Deposits involving the anterior intralaminar nuclei and the striatally projecting cells located lateral to the stria medullaris (anterior intralaminar complex) produced an even, diffuse labelling of the matrix tissue and weak labelling of the striosomes. Injections placed in the ventroanterior, ventrolateral, and ventromedial nuclei (rostral ventral complex) elicited fibrous labelling of matrix tissue that often showed nonstriosomal inhomogeneities. Deposits involving the centromedian and parafascicular nuclei (posterior intralaminar complex) produced a highly variable pattern of matrix labelling that included both homogeneous and decidedly patchy innervations of the extrastriosomal matrix. Each of these lateral thalamostriatal systems showed a similar spatial organization, whereby dorsoventral and mediolateral thalamic axes were roughly preserved in the projection to striatum.     

Corticostriatal and corticosubthalamic input zones from the presupplementary motor area in the macaque monkey: comparison with the input zones from the supplementary motor area

The presupplementary motor area (pre-SMA) is a cortical motor-related area which lies in the medial wall of the frontal lobe, immediately anterior to the supplementary motor area (SMA). This area has been considered to participate in the control of complex forelimb movements in a way different from the SMA. In an attempt to analyze the patterns of projections from the pre-SMA to the basal ganglia, we examined the distributions of pre-SMA inputs in the striatum and the subthalamic nucleus and compared them with the SMA input distributions. To detect morphologically the terminal fields from the pre-SMA and the forelimb region of the SMA, anterograde tracers were injected into such areas that had been identified electrophysiologically in the macaque monkey. Corticostriatal inputs from the pre-SMA were distributed mainly in the striatal cell bridges connecting the rostral aspects of the caudate nucleus and the putamen, as well as in their neighboring striatal portions. These input zones were located, with no substantial overlap, rostral to corticostriatal input zones from the SMA forelimb region. Corticosubthalamic input zones from the pre-SMA were almost localized in the medial aspect of the nucleus, where corticosubthalamic inputs from the SMA forelimb region were also distributed predominantly. However, the major terminal fields from the pre-SMA were centered ventrally to those from the SMA. The present results indicate that the corticostriatal and corticosubthalamic input zones from the pre-SMA appear to be segregated from the SMA-derived input zones. This implies the possibility of parallel processing of motor information from the pre-SMA and SMA in the cortico-basal ganglia circuit.     

Relationship between the corticostriatal terminals from areas 9 and 46, and those from area 8A, dorsal and rostral premotor cortex and area 24c: an anatomical substrate for cognition to action

Our previous data indicate that there are specific features of the corticostriatal pathways from the prefrontal cortex. First, corticostriatal pathways are composed of focal, circumscribed projections and of diffuse, widespread projections. Second, there is some convergence between terminal fields from different functional regions of the prefrontal cortex. Third, anterior cingulate projections from area 24b occupy a large region of the rostral striatum. The goal of this study was to determine whether these features are also common to the corticostriatal projections from area 8A (including the frontal eye field; FEF), the supplementary eye field (SEF), dorsal and rostral premotor cortex (PMdr) and area 24c. Using a new approach of three-dimensional reconstruction of the corticostriatal pathways, along with dual cortical tracer injections, we mapped the corticostriatal terminal fields from areas 9 and 46, 8A-FEF, SEF, PMdr and 24b and c. In addition, we placed injections of retrogradely transported tracers into key striatal regions. The results demonstrated that: (i) a diffuse projection system is a common feature of the corticostriatal projections from different frontal regions; (ii) key striatal regions receive convergent projections from areas 9 and 46 and from areas 8A-FEF, SEF, PMdr and 24c, suggesting a potential pivotal role of these striatal regions in integrating cortical information; (iii) projections from area 24c, like those from area 24b, terminate widely throughout the striatum, interfacing with terminals from several frontal areas. These features of the corticostriatal frontal pathways suggest a potential integrative striatal network for learning.     

Cortical stimulation induces fos expression in intrastriatal striatal grafts

Innervation of intrastriatal grafts of fetal striatal tissue by host corticostriatal projections has been shown in a number of previous studies in rats. In the work reported here, induction of Fos protein in grafted striatal neurons by electrical stimulation of the host frontoparietal cortex has been used as cell-level marker of corticostriatal postsynaptic responses within the striatal grafts. Unilateral cortical stimulation 30 min before sacrifice led to bilateral widespread and intense Fos induction throughout the normal striatum, although the response was somewhat more intense ipsilaterally and in the dorsolateral rostral striatum. In adult rats whose striatum had been lesioned with ibotenic acid 10–12 days prior to implantation of fetal striatal tissue, 3- and 18-month-old striatal grafts showed Fos immunoreactivity in a considerable number of cells after either bilateral, or ipsilateral (30–40% of the density of Fos-immunoreactive cells in the normal striatum) or contralateral cortical stimulation. Double-Fos and -DARPP-32 immunohistochemistry revealed that the Fos-immunoreactive nuclei were concentrated in the DARPP-32-positive (i.e. striatum-like) patches, which contained 60% of the density of Fos-positive nuclei in the normal striatum after either ipsilateral or bilateral stimulation. However, Fos-immunoreactive nuclei were unevenly distributed within the DARPP-32-positive compartment of the graft, with some clusters of Fos-immunoreactive nuclei at 2−3 × the density observed in the normal striatum and other areas with Fos-immunoreactive nuclei present at lower density or absent. Fos induction was also observed in 4-week-old grafts, indicating that functional corticostriatal synaptic contacts develop rapidly. Striatal grafts implanted either in non-lesioned host striatum or in long-term (18 months) lesioned striatum, similarly showed Fos-positive nuclei after cortical stimulation, indicating that host corticostriatal fibers are equally capable of establishing functional synaptic contacts under these conditions. These results indicate that host corticostriatal fibres not only form an axonal network within the graft but also induce postsynaptic responses which may contribute to the observed graft-induced amelioration of lesion-induced behavioural deficits.     

Prefrontal Corticostriatal Afferents Maintain Increased Enkephalin Gene Expression in the Dopamine-denervated Rat Striatum

The cortical contribution to the maintenance of preproenkephalin (PPE) and preprotachykinin (PPT) mRNA levels in the rat striatum was investigated using quantitative in situ hybridization histochemistry. The effects of knifecut transections of the frontal cortical pole on the expression of PPE and PPT mRNA in rat striatal neurons was studied in intact striata and in striata previously denervated by a bhydroxydopamine (6-OHDA) lesion of the mesencephalic dopamine pathways. Lesions of the dopaminergic striatal afferents resulted in marked increases in the mRNA encoding PPE throughout the striatum, including the ventral striatum and nucleus accumbens, while the levels of PPT mRNA were considerably reduced in these structures. Knife-cut lesions of the frontal cortical pole, transecting the prefrontal corticostriatal projection at the level of the foreceps minor, displayed little or no effect on the expression of either PPE or PPT mRNA in the dopamineintact striatum. Conversely, frontal cortical transections performed 4 weeks after the 6-OHDA lesions reversed the 6-OHDA-lesion-induced increase in PPE mRNA in the striatum as well as in the ventral striaturn and nucleus accumbens. The down-regulation of PPE mRNA in the dopaminergically denervated striatum was most pronounced in the medial part, which is the area most densely innervated by the frontal cortical pole. Here, the level of PPE mRNA expression per striatal cell was similar to the intact striatum. In contrast, the cellular expression of PPE mRNA remained up-regulated in the lateral striatum, which receives more sparse innervation from the frontal cortical pole. Cortical transections did not significantly affect the 6-OHDA-lesion-induced down-regulation of PPT mRNA in any of the striatal regions analysed. The present results demonstrate that knifecut transections of the frontal corticostriatal pathway are capable of reversing the increased striatal PPE mRNA levels, but not the decreased PPT mRNA levels, induced by a 6-OHDA lesion of the dopaminergic input. These observations suggest that in the absence of a functional striatal dopamine input, augmented glutamatergic transmission in corticostriatal afferents is necessary to maintain increased levels of PPE mRNA expression, and hence also enkephalin synthesis, in striatal projection neurons.     

Species-specific patterns of glycoprotein expression in the developing rodent caudoputamen: Association of 5′-nucleotidase activity with dopamine islands and striosomes in rat,but with extrastriosomal matrix in mouse

The glycoprotein 5′-nucleotidase is a cell surface phosphatase and represents a new marker for striosomes in the adult rat caudoputamen. We report here on its developmental expression in the rat and mouse striatum, and show an unexpected converse 5′-nucleotidase chemoarchitecture of the caudoputamen in these closely related species. In the rat, 5′-nucleotidase activity was first visible as neuropil staining in tyrosine hydroxylase-positive dopamine islands of the midstriatum on postnatal day 1, and by the end of the first postnatal week, 5′-nucleotidase-positive dopamine islands also appeared rostrally. This compartmental pattern persisted thereafter, so that in adult animals, in all but the caudal caudoputamen, zones of enhanced 5′-nucleotidase staining were restricted to calbindin-D_28k-poor striosomes. Weak 5′-nucleotidase activity also emerged in the matrix. In striking contrast, in the mouse striatum, enhanced 5′-nucleotidase activity was preferentially associated with extrastriosomal tissue. Enzymatic reaction first appeared on embryonic day 18, and developed over the first postnatal week into a mosaic pattern in which the matrix was stained but the dopamine islands were unstained. The matrix staining itself was heterogeneous. After the second postnatal week, most of the caudoputamen was stained, and in adult mice only rostral striosomes expressed low 5′-nucleotidase activity. We conclude that in rats, 5′-nucleotidase represents one of the few substances that maintains a preferential dopamine island/striosome distribution during striatal development. In mice, 5′-nucleotidase activity is expressed preferentially in the matrix during development, and its compartmental pattern is gradually lost with maturation, except very rostrally. These findings do not suggest an instructive role of the enzyme in striatal compartment formation in either species, but do suggest the possibility that 5′-nucleotidase contributes to the differentiation of striatal compartments during development. © 1993 Wiley-Liss, Inc.     

The associative striatum: organization of cortical projections to the dorsocentral striatum in rats

The dorsocentral striatum (DCS) is the major site of input from medial agranular cortex (AGm) and has been implicated as an associative striatal area that is part of a cortical-subcortical circuit involved in multimodal spatial functions involving directed attention. Anterograde axonal tracing was used to investigate the spatial organization of corticostriatal projections to DCS. Injections of biotinylated dextran amine were made into several cortical areas known to project to DCS based on retrograde tracing data. These included areas AGm, lateral agranular cortex (AGl), orbital cortex, posterior parietal cortex (PPC), and visual association cortex. We discovered a previously undescribed geometry whereby the projection from AGm is prominent within DCS and the main corticostriatal projections from areas other than AGm are situated around the periphery of DCS: visual association cortex dorsomedially, PPC dorsally, AGl laterally, and orbital cortex ventrally. Each of these cortical projections is also represented by less dense aggregates of terminal labeling within DCS, organized as focal patches and more diffuse labeling. Because these cortical areas are linked by corticocortical connections, the present findings indicate that interconnected cortical areas have convergent terminal fields in the region of DCS. These findings suggest that DCS is a central associative region of the dorsal striatum characterized by a high degree of corticostriatal convergence.     

Topographical organization and relationship with ventral striatal compartments of prefrontal corticostriatal projections in the rat.

The anterograde tracer Phaseolus vulgaris-leucoagglutinin was used to examine the topographical organization of the projections to the striatum arising from the various cytoarchitectonic subdivisions of the prefrontal cortex in the rat. The relationship of the prefrontal cortical fibres with the compartmental organization of the ventral striatum was assessed by combining PHA-L tracing and enkephalin-immunohistochemistry. The prefrontal cortex projects bilaterally with an ipsilateral predominance to the striatum, sparing only the lateral part of the caudate-putamen complex. Each of the cytoarchitectonic subfields of the prefrontal cortex has a longitudinally oriented striatal terminal field that overlaps slightly with those of adjacent prefrontal areas. The projections of the medial subdivision of the prefrontal cortex distribute to rostral and medial parts of the striatum, whereas the lateral prefrontal subdivision projects to more caudal and lateral striatal areas. The terminal fields of the orbital prefrontal areas involve midventral and ventromedial parts of the caudate-putamen complex. The projection of the ventral orbital area overlaps with that of the prelimbic area in the ventromedial part of the caudate-putamen. In the "shell" region of the nucleus accumbens, fibres arising from the prelimbic area concentrate in areas of high cell density that are weakly enkephalin-immunoreactive, whereas fibres from the infralimbic area avoid such areas. Rostrolaterally in the "core" region of the nucleus accumbens, fibres from deep layer V and layer VI of the dorsal part of the prelimbic area avoid the enkephalin-positive areas surrounding the anterior commissure and distribute in an inhomogeneous way over the intervening moderately enkephalin-immunoreactive compartment. The other prefrontal afferents show only a preference for, but are not restricted to, the latter compartment. In the border region between the nucleus accumbens and the ventromedial part of the caudate-putamen complex, patches of strong enkephalin immunoreactivity receive prefrontal cortical input from deep layer V and layer VI, whereas fibres from more superficial cortical layers project to the surrounding matrix. Individual cytoarchitectonic subfields of the prefrontal cortex thus have circumscribed terminal domains in the striatum. In combination with data on the organization of the midline and intralaminar thalamostriatal and thalamoprefrontal projections, the present results establish that the projections of the prefrontal cortical subfields converge in the striatum with those of their midline and intralaminar afferent nuclei. The present findings further demonstrate that the relationship of the prefrontal corticostriatal fibres with the neurochemical compartments of the ventral striatum can be influenced by both the areal and the laminar origin of the cortical afferents, depending on the particular ventral striatal region under consideration.