Corticostriatal Projections Research Articles

Absence of basal ganglia amino acid neuron deficits in schizophrenia in three collections of brains

Amino acid (glutamatergic, GABAergic) neuron deficiency theories of schizophrenia offer plausible explanations of pathogenesis. However, reports of disease-related reductions in amino acid synthesizing enzymes in post-mortem brains are contradictory. We measured neuronal uptake sites for γ-aminobutyric acid (GABA; [ 3H]nipecotic acid binding) and nerve terminal/glial uptake sites for l-glutamate ( d-[ 3H]aspartate binding) in three independent groups of post-mortem brains from patients with schizophrenia and control subjects. Measurements were also made of the phencyclidine site of the glutamate N- methyl- d- aspartate (NMDA) receptor. Samples from patients showed no reductions in the binding of [ 3H]nipecotic acid or d-[ 3H]aspartate in caudate, putamen or globus pallidus. On the contrary, some increased binding of both ligands was observed in patients in many comparisons with controls. There were no clear-cut changes in NMDA receptor binding. The most consistent change in the brain sets was increased [ 3H]nipecotic acid binding in caudate-putamen. This could be due to neuroleptic treatment. The findings produce no evidence that schizophrenia involves major loss of GABA neuron terminals in the basal ganglia or losses of corticostriatal glutamatergic projections.

Divergent corticostriatal projections from a single cortical column in the somatosensory cortex of rats

We injected biotinylated dextran amine (BDA) into single vibrissal `barrels' of primary somatosensory (SI) cortex and reconstructed the topography of labelled varicosities in the dorsolateral caudate–putamen. Plots of labelled varicosities revealed densely-packed clusters of corticostriatal arborizations along the dorsolateral edge of the caudate–putamen and sparsely-packed arborizations more medially. The medial and lateral clusters of labelled terminals were separated by regions of unlabelled neuropil and lead us to conclude that a single cortical column sends divergent projections to multiple regions of the caudate–putamen.

Corticostriatal input zones from the cingulate motor area in the monkey

The corticostriatal projection in rat neostriatal grafts was studied by using the axonal transport ofPhaseolus vulgaris-leucoagglutinin. The neostriatal primodia from 15–18-day embryos were used to make a cell suspension which was implanted unilaterally into the rat neostriatum 3–5 days after kainic acid lesion. Two to four months later, regions of the frontal cortex ipsilateral to the grafts were injected iontophoretically withPhaseolus valgaris-leucoagglutinin.There were manyPhaseolus valgaris-leucoagglutinin labeled cortical fibers in the host neostriatum. Although the density of labeled fibers in the grafts was much lower than that in the surrounding host tissue, some fibers could be seen to enter the grafts and form terminal arborizations. The morphology of labeled fibers in the graft differed from that of corticostriatal fibers from the same injection but distributing in the host neostriatum. The labeled fibers in the host neostriatum arborized in an extended pattern, branching infrequently and making most of their synapses en passant at varicosities along their courses. The labeled fibers in the grafts made more dense arborizations with many short branches that formed clusters of terminals confined to small foci along their courses. The cellular composition and the structure of the neuropil in the neostriatal grafts were similar to that of the neostriatum. As those in the host, labeled corticostriatal terminals in the grafts contained densely packed round vesicles and made asymmetric synapses on dendritic spines, dendritic shafts and somata. A quantitative analysis, however, revealed that the distribution of postsynaptic elements of labeled boutons in the grafts was different from that in the hosts. More than 90% of the labeled cortical terminals in the host neostriatum contacted dendritic spines whereas only 47% of the labeled terminals in the grafts contacted spines, and 50% of them terminated on the dendritic shafts.The present study provides direct anatomic evidence to demonstrate the restoration of the corticostriatal projection in grafts. The difference in the distribution of postsynaptic elements in the grafts and the hosts may represent a response to the decreased innervation density of cortical inputs to the graft tissue, and may contribute to the recovery of corticostriatal responses by increasing the effectiveness of transmission by the fibers that do grow into the graft and form contacts there.

Up and Down States in Striatal Medium Spiny Neurons Simultaneously Recorded with Spontaneous Activity in Fast-Spiking Interneurons Studied in Cortex–Striatum–Substantia Nigra Organotypic Cultures

In vivo intracellular spontaneous activity in striatal medium spiny (MS) projection neurons is characterized by "up" and "down" states. How this type of activity relates to the neuronal activity of striatal fast-spiking (FS) interneurons was examined in the presence of nigral and cortical inputs using cortex-striatum-substantia nigra organotypic cultures grown for 45 +/- 4 d. The nigrostriatal projection was confirmed by tyrosine hydroxylase immunoreactivity. Corticostriatal (CS) projection neurons, striatal MS neurons, and FS neurons were intracellularly recorded and morphologically and electrophysiologically characterized. Intracellular spontaneous activity in the cultures consisted of intermittent depolarized periods of 0.5-1 sec duration. Spontaneous depolarizations in MS neurons were restricted to a narrow membrane potential range (up state) during which they occasionally fired single spikes. These up states were completely blocked by the glutamate antagonist CNQX. In FS interneurons, depolarized periods were characterized by large membrane potential fluctuations that occupied a wide range between rest and spike threshold. Also, FS interneurons spontaneously fired at much higher rates than did MS neurons. Simultaneous intracellular recordings established that during spontaneous depolarizations MS neurons and FS interneurons displayed correlated subthreshold neuronal activity in the low frequency range. These results indicate that (1) the CS projection neurons, striatal MS neurons, and FS interneurons grown in cortex-striatum-substantia nigra organotypic cultures show morphological and electrophysiological characteristics similar to those seen in vivo; (2) striatal MS neurons but not FS interneurons show an up state; (3) striatal MS neurons and FS interneurons receive common, presumably cortical inputs in the low frequency range. Our results support the view that the cortex provides a feedforward inhibition of MS neuron activity during the up state via FS interneurons.

Layer V neurons bear the majority of mRNAs encoding the five distinct dopamine receptor subtypes in the primate prefrontal cortex.

In situ hybridization histochemistry was used to determine the laminar distribution of D1, D2, D3, D4, and D5 dopamine receptor mRNAs in the primate prefrontal cortex and to compare striatal and cortical levels of these messages within the same tissue sections. All five subtypes of dopamine receptor mRNA are present in both the monkey striatum and the cerebral cortex but in different proportions within each structure. Thus, levels of D1 and D2 mRNAs are noticeably stronger in the striatum than in the cortex, whereas D4 and D5 expression is clearly higher in the cortex. The D3 transcripts appear nearly equivalent in the striatum and the cortex. A major finding is that, within the prefrontal cortex, mRNAs encoding all dopamine receptor subtypes are expressed most strongly in layer V. This laminar pattern of mRNA distribution does not hold in all cortical regions. The relatively high levels of mRNAs encoding known dopamine receptor subtypes in the primate cerebral cortex, including the D4 receptor, underscore the importance of this structure as a target for therapeutic actions of antipsychotic drugs. Further, their prominence in layer V of the prefrontal cortex, which contains the corticostriatal and corticotectal projection neurons, provides a neural basis for dopaminergic regulation of the descending control systems.

Regulation of the polysialylated form of the neural cell adhesion molecule in the developing striatum: effects of cortical lesions.

Early in development, the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is expressed by growth cones, neuronal processes, and neuronal cell bodies. In rat striatum, PSA-NCAM expression becomes progressively restricted to pre- and postsynaptic membranes and is undetectable by postnatal day 25 (P25), i.e., after corticostriatal synaptogenesis. This study examined the effects of cortical lesions performed on P14, when the corticostriatal projection is already primarily unilateral and cortical inputs have not yet formed asymmetric synapses on striatal neurons. Rats were killed on P25, and PSA-NCAM expression was examined by immunoblotting and immunohistochemistry with light and electron microscopy. In contrast to the case in controls, PSA-NCAM expression was maintained in the striatum of lesioned pups. Ultrastructural studies showed that PSA-NCAM was present 1) in growth cone-like structures and neuronal processes and 2) in striatal neurons. Together with the presence of growth cones, the observation that the number of asymmetric synapses was unchanged in the denervated striatum suggests that axonal sprouting occurred in response to the lesion. This was confirmed by axonal labeling in the denervated striatum after injection of Fluoro-Ruby in the contralateral cortex. The data indicate that P14 cortical lesions affect PSA-NCAM expression in the developing striatum 1) by inducing a robust axonal plasticity resulting in the presence of immature presynaptic elements that contain PSA-NCAM and 2) by delaying the loss of PSA-NCAM expression in striatal neurons, suggesting that the lesion affects the time course of striatal maturation.

Organization of Corticostriatal and Corticoamygdalar Projections Arising from the Anterior Inferotemporal Area TE of the Macaque Monkey: APhaseolus vulgarisLeucoagglutinin Study

Corticostriatal and corticoamygdalar projections arising from area TE of the macaque monkey were studied by focal injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the dorsolateral and ventromedial subdivisions of the anterior TE (TEad and TEav, respectively). This approach yielded several new results. First, the global distributions of labeled terminals revealed that both TEad and TEav projected to the ventrocaudal striatum, including the tail of the caudate nucleus and the adjacent ventral putamen, and the dorsolateral aspect of the deep amygdaloid nuclei. TEav also projected to the medial basal nucleus of the amygdala and the ventral striatum. Second, the reconstructed single axons (n = 18) demonstrated that some axons originating from TEav or TEad projected simultaneously to the ventrocaudal striatum and the dorsolateral aspect of the deep amygdaloid nuclei by giving off collaterals. TEav axons projected to the medial basal nucleus of the amygdala also had collaterals projecting to the perirhinal cortex or area TG. And third, it was revealed that the axons originating from a focal TEav or TEad projected to a restricted territory (3.4-3.6 mm rostrocaudally) in the ventrocaudal striatum with four to six dispersed, rostrocaudally elongated, rod-like modules. Individual axons with multiple arbors innervated many of these modules. These findings add the evidence that the anterior part of TE is anatomically heterogeneous and suggest that the deep amygdaloid nuclei may be functionally dissociated, with the dorsolateral aspect more closely related to the ventrocaudal striatum and the medial basal nucleus more closely related to the perirhinal cortex.

Pigeon Basal Ganglia: Insights into the Neuroanatomy Underlying Telencephalic Sensorimotor Processes in Birds

This paper reviews the organization of the avian and mammalian striatum. The striatum receives input from virtually the entire rostrocaudal and mediolateral expanse of the cerebral cortex. The corticostriatal projections appear to be glutamatergic, forming excitatory synapses in the striatum. Another major projection to the avian striatum that also appears to be glutamatergic stems from a set of nuclei in the dorsal zone of the avian thalamus that are comparable to the mammalian intralaminar, mediodorsal, and midline nuclei. Furthermore, the striatum receives a massive projection from dopaminergic neurons of the ventral tegmental area and substantia nigra in the midbrain tegmentum. In return, the midbrain tegmentum receives a direct GABAergic/substance P-ergic/ dynorphinergic projection from the striatum, as well as an indirect one formed by GABAergic/substance P-ergic/ dynorphinergic and GABA-ergic/enkephalinergic striatal neurons projecting to the pallidum in the first step, and pallidal GABAergic/LANT6/parvalbumin neurons projecting to the midbrain tegmentum in the second step. In addition to its projection neurons, the striatum possesses GABAergic and cholinergic interneurons. One motor output pathway of the striatum runs via the pallidum and dorsal thalamic ventral tier nulei to the motor cortex. In addition to this pathway, birds possess a major descending pathway from the basal ganglia to the tectum via the GABAergic nucleus spiriformis lateralis in the pretectum. On hodological and topological grounds, similar nuclei, although not GABAergic, can be found in mammals. Finally, an other striatal motor output is formed by a sequential GABAergic pathway from the basal ganglia via the substantia nigra to the tectum. In conclusion, it appears that the organization of the avian and mammalian basal ganglia is similar rather than different.

Effect of electrical stimulation of the cerebral cortex on the expression of the fos protein in the basal ganglia

The protein Fos is a transcription factor which is quickly induced in response to a variety of extracellular signals. Since this protein is expressed in a variety of neuronal systems in response to activation of synaptic afferents, it has been suggested that it might contribute to activity-dependent plasticity in neural networks. The present study investigated the effect of cortical electrical stimulation on the expression of Fos in the basal ganglia in the rat, a group of structures that participate in sensorimotor learning. Results show that the repetitive application of electrical shocks in restricted areas of the cerebral cortex induces an expression of Fos mostly confined to the striatum and the subthalamic nucleus. The induction which can be elicited from different cortical areas (sensorimotor, auditory and limbic areas) does not require particular temporal patterns of stimulation but rather depends on the total number of shocks delivered during a given period of time. Moreover, it appears to be rather independent of the number of spikes discharged by the activated cells. In the striatum, the distribution of immunoreactive neurons is precisely delineated and conforms to the known topographical organization of stimulated corticostriatal projections. As demonstrated using a variety of double labelling techniques (combination of the immunocytochemical detection of Fos with the autoradiography of μ opioid receptors, calbindin immmunocytochemistry, in situ hybridization of preproenkephalin and preprotachykinin A messenger RNAs), striatal neurons which express Fos are mostly localized in the matrix compartment and concern equally enkephaline and substance P containing efferent neurons. In the subthalamic nucleus, Fos expression evoked by cortical stimulation is also confined to discrete regions of the nucleus, the localizations corresponding to the primary projection site of the stimulated cortical cells. These results indicate that in addition to its phasic synaptic influence on the basal ganglia, the cerebral cortex could exert a long-term effect on the functional state of this system via a genomic control. Since the basal ganglia are involved in sensorimotor learning and motor habit formation, it is tempting to speculate that the activity-dependent Fos induction at corticostriatal and subthalamic synapses may contribute to consolidate the functionality of the neuronal networks activated during the completion of given motor tasks.

Corticostriatal input zones from proximal and distal forelimb representations of monkey primary motor cortex

The present study was undertaken to determine in the rat the topography of the neostriatal projections originating from the motor cortex. For that purpose, anterograde tracers (Phaseolus vulgaris leucoagglutinin: PHA-L; wheat germ agglutinin conjugated to horseradish peroxidase: WGA-HRP) were deposited in discrete cortical sites physiologically identified by microstimulation. Five major motor areas were considered in this study: the rostral (RFL) and caudal (CFL) forelimb areas, the hindlimb (HL) area, the vibrissae motor-frontal eye field (V-FEF) region and the jaw, lips and tongue (JLT) area (according to the nomenclature of Neafsey et al.). The results indicate that functionally different regions of the motor cortex project to different sectors of the caudate putamen (CPU). All 3 distinct limb areas RFL, CFL and HL project to the dorsolateral quarter of the CPU, V-FEF area projects to the dorsomedial quarter, whereas the JLT area projects to the ventrolateral quarter. The pattern of terminal labeling is relatively consistent, whatever the cortical area in which the tracer is deposited. This pattern is characterized by the presence of two or more labeled bands which are obliquely oriented along a ventrolateral-dorsomedial axis. Control experiments were also undertaken in which a retrograde tracer (WGA-HRP) was deposited in various neostriatal loci. The results are congruent with the findings of the anterograde study and further indicate that a given neostriatal sector receives projections from cytoarchitectonically different but functionally related regions of the neocortex. The somatotopic features of both motor and somatosensory corticostriatal projections appear to be in register. In addition, the striatal distribution of motor cortical fibers was compared in 6 experimental cases to the compartmental subdivision of the striatum in patches and matrix, following immunohistochemichal localization of calbindin 28 kDa. The calbindin-immunoreactivity is extremely weak in the dorsolateral sector but is higher in the central and ventrolateral parts of the CPU. In these deep striatal regions receiving fibers from V-FEF, JLT and, to a lesser extent, from the limb areas, the cortical fibers are mostly directed to the matrix. The band-like organization of the projection from the motor cortex is correlated to the patch-matrix organization. The patches correspond to the bands of low density of terminal fibers and the matrix to the bands of high terminal density. The present results provide an anatomical basis to both electrophysiological and behavioral observations suggesting that functional distinctions can be established between subregions of the striatum.

Differential distribution of tyrosine hydroxylase fibers on small and large neurons in layer II of anterior cingulate cortex of schizophrenic brain.

A series of recent postmortem investigations of the anterior cingulate cortex in schizophrenic brain have suggested that there may be a loss and/or impairment of inhibitory interneurons in layer II. It has been postulated that changes of this type could secondarily result in a relative increase of dopaminergic inputs to GABAergic interneurons. To test this hypothesis, an immunoperoxidase technique was developed to extensively and reliably visualize tyrosine hydroxylase-immunoreactive (TH-IR) varicose fibers in human postmortem cortex. This method has been applied to the anterior cingulate (ACCx; Brodmann area 24) and prefrontal (PFCx: Brodmann area 10) cortices from a cohort of 15 normal control and 10 schizophrenic cases. The number of TH-IR varicosities in contact with large neurons (LN), small neurons (SN), and neuropil (NPL) was blindly analyzed using a computer-assisted microscopic technique. There was no significant difference in density of TH-IR varicosities in apposition with either LN or SN cell bodies observed in either ACCx or PFCx of schizophrenics when compared to normal controls. The density of varicosities was significantly reduced in NPL of layers V and VI in ACCx, but 2 neuroleptic-free cases did not show this change, suggesting that these decreases of TH-IR varicosities may be related to antipsychotic effects on corticostriatal projection cells in this region. When the density of TH-IR varicosities on SNs was compared to that observed on LNs, both groups showed a higher density on SNs. In ACCx, this pattern was much more pronounced for the schizophrenic group, particularly in layer II where the density on SNs was three times higher than that for LNs (P = 0.01). Unlike the changes in layer V, this latter change in layer II showed no relationship to neuroleptic exposure. There was a positive correlation between age and the density of TH-IR varicosities on SNs of layer II in ACCx; however, the patients were younger than the controls and would have been expected to show a lower density, rather than a higher one, if age considerations had accounted for the group differences. Overall, the results reported here suggest that there are no gross differences in the distribution of TH-IR varicosities in various laminae of the dorsolateral prefrontal cortex. In the anterior cingulate region, however, there may be a significant shift in the distribution of TH-IR varicosities from large neurons to small neurons that occurs selectively in layer II of schizophrenic subjects. Using size criteria, the majority of small neurons are likely nonpyramidal, while the majority of large neurons are predominantly pyramidal in nature. Taken together with other accumulating evidence of preferential abnormalities in this lamina of the cingulate region, the findings reported here are consistent with a model of schizophrenia in which a subtle "miswiring" of ventral tegmental inputs may result in a relative, though not absolute, hyperdopaminergic state with respect to an impaired population of GABAergic interneurons.

1551 Corticostriatal input from the presupplementary motor area: Its spatial segregation from supplementary motor area input

The present study was undertaken to determine in the rat the topography of the neostriatal projections originating from the motor cortex. For that purpose, anterograde tracers (Phaseolus vulgaris leucoagglutinin: PHA-L; wheat germ agglutinin conjugated to horseradish peroxidase: WGA-HRP) were deposited in discrete cortical sites physiologically identified by microstimulation. Five major motor areas were considered in this study: the rostral (RFL) and caudal (CFL) forelimb areas, the hindlimb (HL) area, the vibrissae motor-frontal eye field (V-FEF) region and the jaw, lips and tongue (JLT) area (according to the nomenclature of Neafsey et al.). The results indicate that functionally different regions of the motor cortex project to different sectors of the caudate putamen (CPU). All 3 distinct limb areas RFL, CFL and HL project to the dorsolateral quarter of the CPU, V-FEF area projects to the dorsomedial quarter, whereas the JLT area projects to the ventrolateral quarter. The pattern of terminal labeling is relatively consistent, whatever the cortical area in which the tracer is deposited. This pattern is characterized by the presence of two or more labeled bands which are obliquely oriented along a ventrolateral-dorsomedial axis. Control experiments were also undertaken in which a retrograde tracer (WGA-HRP) was deposited in various neostriatal loci. The results are congruent with the findings of the anterograde study and further indicate that a given neostriatal sector receives projections from cytoarchitectonically different but functionally related regions of the neocortex. The somatotopic features of both motor and somatosensory corticostriatal projections appear to be in register. In addition, the striatal distribution of motor cortical fibers was compared in 6 experimental cases to the compartmental subdivision of the striatum in patches and matrix, following immunohistochemichal localization of calbindin 28 kDa. The calbindin-immunoreactivity is extremely weak in the dorsolateral sector but is higher in the central and ventrolateral parts of the CPU. In these deep striatal regions receiving fibers from V-FEF, JLT and, to a lesser extent, from the limb areas, the cortical fibers are mostly directed to the matrix. The band-like organization of the projection from the motor cortex is correlated to the patch-matrix organization. The patches correspond to the bands of low density of terminal fibers and the matrix to the bands of high terminal density. The present results provide an anatomical basis to both electrophysiological and behavioral observations suggesting that functional distinctions can be established between subregions of the striatum.

Corticostriatal innervation of the patch and matrix in the rat neostriatum

The distribution of rat corticostrial axons in the patch (striosome) and matrix compartments of the neostriatum was studied by using axonal labeling with biotinylated dextran amine (BDA) and identifying patch and matrix in the same section with calbindin immunocytochemistry. Small injections of BDA were made in the anterior cingulate, medial agranular, lateral agranular, or somatosensory cortex. Each area projected to both the patch and matrix compartments, except for the somatosensory cortex, which had only matrix projections. Within the remaining cortical areas, injections in layers Vb and VI preferentially labeled axons in patches whereas injections in layers III-Va preferentially labeled matrix axons. Axons from these injections formed varicosities preferentially, but not exclusively, in one compartment. There was a population of axons that crossed compartmental boundaries and arborized in both patch and matrix. Two distinct patterns of corticostriatal axonal arborizations were observed. Small, discrete foci of innervation were seen in the patch compartment and in some regions of the matrix. The focal arborizations in the matrix were observed through the rostrocaudal extent of the neostriatum but were most obvious in the caudal one-third. They resembled the matrisomes observed in cat and primate corticostriatal projections. The second pattern of innervation consisted of extended axonal arborizations that covered large regions of the rostral neostriatal matrix. These results support the concept of multiple classes of corticostriatal neurons having different targets within the neostriatum, following different topographical rules, and having different but overlapping distributions across cortical areas. © 1996 Wiley-Liss, Inc.

Corticostriatal innervation of the patch and matrix in the rat neostriatum.

The distribution of rat corticostrial axons in the patch (striosome) and matrix compartments of the neostriatum was studied by using axonal labeling with biotinylated dextran amine (BDA) and identifying patch and matrix in the same section with calbindin immunocytochemistry. Small injections of BDA were made in the anterior cingulate, medial agranular, lateral agranular, or somatosensory cortex. Each area projected to both the patch and matrix compartments, except for the somatosensory cortex, which had only matrix projections. Within the remaining cortical areas, injections in layers Vb and VI preferentially labeled axons in patches whereas injections in layers III-Va preferentially labeled matrix axons. Axons from these injections formed varicosities preferentially, but not exclusively, in one compartment. There was a population of axons that crossed compartmental boundaries and arborized in both patch and matrix. Two distinct patterns of corticostriatal axonal arborizations were observed. Small, discrete foci of innervation were seen in the patch compartment and in some regions of the matrix. The focal arborizations in the matrix were observed through the rostrocaudal extent of the neostriatum but were most obvious in the caudal one-third. They resembled the matrisomes observed in cat and primate corticostriatal projections. The second pattern of innervation consisted of extended axonal arborizations that covered large regions of the rostral neostriatal matrix. These results support the concept of multiple classes of corticostriatal neurons having different targets within the neostriatum, following different topographical rules, and having different but overlapping distributions across cortical areas.

Anatomical and functional evidence for lesion-specific sprouting of corticostriatal input in the adult rat.

Previous studies in our laboratory have shown that cortical lesions induced by thermocoagulation of pial blood vessels, but not by acute aspiration, result in 1) the preservation of control levels of the growth-associated protein (GAP)-43 and 2) a prolonged increase in neurotransmitter gene expression in the denervated dorsolateral striatum. We have examined whether corticostriatal projections from the spared homotypic contralateral cortex contribute to these effects. Adult rats received either a thermocoagulatory or aspiration lesion of the cerebral cortex and, after 30 days, received an injection of the anterograde tracer, Fluoro-Ruby, in the contralateral homotypic cortex. Rats were killed 7 days later, and labeled fibers were examined with fluorescence microscopy in the ipsilateral and contralateral striata. Ipsilateral corticostriatal projections were detected in lesioned and unlesioned rats. Numerous labeled fibers were detected in the contralateral striatum of thermocoagulatory-lesioned but not aspiration-lesioned or control animals, suggesting that contralateral cortical neurons may undergo axonal sprouting in the denervated striatum following a thermocoagulatory lesion of the cortex. To determine whether contralateral corticostriatal fibers play a role in the changes in striatal gene expression induced by the thermocoagulatory lesions, the effects of aspiration lesions, as well as unilateral and bilateral thermocoagulatory lesions of the cortex were compared. Confirming previous results, striatal enkephalin mRNA levels were increased after a unilateral thermocoagulatory lesion. However, they were unchanged after aspiration or bilateral thermocoagulatory lesions, suggesting that sprouting or overactivity of contralateral corticostriatal input contributes to the increase seen after unilateral thermocoagulatory lesions.

Overlapping corticostriatal projections from the supplementary motor area and the primary motor cortex in the macaque monkey: an anterograde double labeling study.

The purpose of the present study was to determine if the cortical efferents from homologous body regions of the supplementary motor area (SMA) and the primary motor cortex (MI) project to separate or to overlapping regions in the striatum. In order to investigate the dual corticostriatal projections, we employed an anterograde double labeling paradigm in which two tracers could be simultaneously detected in the same histological section. Prior to the injections, the forelimb representation in the two cortical motor areas was identified by using intracortical microstimulation in four Japanese monkeys (Macaca fuscata). Multiple injections of biotinylated dextran amine (BDA) were made into the forelimb regions of MI and wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) was injected into the arm region of the SMA. In additional animals, the tracers were reversed such that BDA was injected into the SMA and WGA-HRP was injected into the MI. The tissue was processed sequentially using different chromogens in order to visualize both tracers in a single section. We analyzed the distribution of the ipsilateral anterograde label. The striatal labeling from each cortical area basically consisted of a wide band of patchy dense labeling interrupted by lighter labeling. The SMA striatal projections were located mainly within the putamen, distributing from the level of the anterior commissure to the most posterior extent of the putamen. At an intermediate level, the label spread obliquely from the ventrolateral edge of the putamen dorsomedially as far as the lateral edge of the caudate nucleus. The label from the MI was observed in comparable portions of the putamen, although the SMA projections were shifted more anterior and dorsomedial to the MI projections and the heaviest projections from the SMA and the MI were separately located. On the basis of the double anterograde labeling technique, we found considerable overlap mainly in the central portion of the putamen from the SMA and MI forelimb representation. These results suggest that the homologous body regions of the SMA and MI send widespread, and substantially overlapping projections, to portions of the striatum.

Involvement of the caudal striatum in auditory processing: c- fos response to cortical application of picrotoxin and to auditory stimulation

The topographical organization of corticostriatal connections have been postulated to follow a longitudinal pattern, each cortical area projecting on a longitudinal strip stretching along the whole rostro-caudal axis of the striatum. However, compared to the rostral striatal region, the caudal striatum exhibits distinct features in terms of connectivity and neuronal phenotype. The induction of c- fos expression in the striatum by cortical activation or sensory stimulation may throw more light on these functional corticostriatal relationships. In the present study, we examined the effects of cortical activation by local application of picrotoxin on the Fos-immunoreactivity (Fos-IR) in the striatum of the mouse, with special reference to the caudal part of the striatum. Activation of the auditory cortex induced a dense ipsilateral Fos-IR restricted to the caudal striatum, i.e., in the caudo-medial striatum and in the caudal part of fundus striati, and a very sparse labelling in the medial region of the rostral striatum. Conversely, activation of both sensori-motor and visual cortices only resulted in Fos-IR in the main rostral part of the striatum, without response in the caudal extremity of the striatum. On the other hand, visual or auditory stimulation in awake animals failed to induce c- fos expression in the striatum. However, using quantitative in-situ hybridization for c- fos mRNA, we found that auditory, but not visual stimulation significantly potentiated the c- fos response to the D1 agonist SKF 38393 (2 mg/kg, i.p.) in the caudal part of the striatum. These functional observations suggest that, despite a more widespread cortico-striatal connection pattern deduced from tracing experiments, the strongest functional projections from the auditory system mainly converge onto a restricted part of the caudal striatum, according to a connection pattern that is reminiscent of the transverse segmentation proposed in early lesioning studies of corticostriatal projections.

The lamellar organization of the rat substantia nigra pars reticulata: segregated patterns of striatal afferents and relationship to the topography of corticostriatal projections.

The striatonigral pathway provides one of the most direct routes for information flow through the basal ganglia system. Via this pathway information from sensory, motor and associative areas of the cerebral cortex are routed to a variety of thalamocortical and brainstem networks involved in the organization of motor behaviour. In a previous analysis of the rat substantia nigra pars reticulata we have shown that the nigral cells which project to thalamus, tectum and tegmentum are topographically ordered along a series of curved laminae. Extending these observations, the present study examined how striatal regions related to particular areas of the cerebral cortex innervate the lamellar keyboard of nigral output neurons. For this purpose, small microiontophoretic injections of wheat germ agglutinin conjugated to horseradish peroxidase were performed in the striatum and the distribution of retrogradely-labelled cells in the cerebral cortex and anterogradely-labelled axons in the substantia nigra were conjointly examined. The results indicate that with the exception of the striatal region related to the allocortex, all the various components of the striatal functional mosaic are represented in the substantia nigra pars reticulata. This representation is organized under the form of longitudinal bands which compose a series of curved laminae enveloping a core located dorsolaterally in the substantia nigra. The striatal mapping in substantia nigra pars reticulata is such that the projections of the auditory and visual compartments are confined to the most ventral lamina. More dorsally, an ordered representation of the body is achieved by the nigral lamination. The oral and perioral body parts are centred on the dorsolateral core and the more distal parts of the face and limbs are progressively set out in more peripheral laminae. In the region affiliated to the prefrontal cortex, the dorsal cingulate district innervate a ventromedial lamina, the prelimbic/insular district lie dorsal to it. Projections from lateral orbital and insular compartments extend laterally along the dorsal margin of the pars reticulata. Since the "onion-like" distribution of striatal inputs is precisely the form observed in the distribution of nigral efferent neurons, the present observations favour the view that the nigral lamination underlies formation of specific input-output channels of processing. Evidence is considered that these channels are specialized for particular classes of movements or behaviours and integrate the various information relevant to the completion of these movements or behaviours.

Corticostriatal projections from layer V cells in rat are collaterals of long-range corticofugal axons

Corticostriatal projections arising from the infragranular layers of the motor and second somatosensory cortices were studied in rats after labeling small pools of neurons with biocytin. Camera lucida reconstruction of 263 fibers arising from laminae V and VI revealed that all corticostriatal projections derive from collaterals of lamina V cells whose main axons descend into the cerebral peduncle. In contrast, lamina VI cells do not branch upon the striatum, but upon the thalamus. Together with the results obtained in previous tracing studies, the present data raise the possibility that no neuron is exclusively corticostriatal. We therefore propose that all corticostriatal projections are collaterals given off by the axons of two types of neurons: layer V cells whose main axon project to the brainstem and/or spinal cord, and layer III cells that project to the contralateral hemisphere.

Increased neostriatal tyrosine hydroxylation during stress: role of extracellular dopamine and excitatory amino acids.

We examined the regulation of neostriatal tyrosine hydroxylation during acute stress, testing the hypothesis that excitatory amino acids (EAAs) contribute to the stress-evoked increase in dopamine (DA) synthesis. Dialysis probes implanted into neostriatum permitted delivery of drugs and sampling of extracellular fluid. Rats were exposed to 30 min of intermittent tail shock during infusion of an inhibitor of aromatic amino acid decarboxylase (AAAD), NSD-1015 (100 microM), and DOPA was measured in the dialysate. Tail shock was applied beginning either 15 min after the onset of NSD-1015 treatment (the initial rate of DOPA accumulation) or 75 min after the onset of treatment (when DOPA had approached steady state). Tail shock increased the steady-state levels of extracellular DOPA in neostriatum (+40%). However, there was no change in the initial rate of DOPA accumulation unless animals also received the D2 receptor antagonist eticlopride (50 nM), in which case an increase was observed (+228%). The impact of tail shock on the steady-state level of DOPA was attenuated by the D2 agonist quinpirole (100 microM), or by 2-amino-5-phosphonovalerate (APV) (100 microM) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (100 microM), EAA antagonists acting at NMDA or D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate (AMPA) receptors, respectively. These data suggest that acute stress normally has little effect on tyrosine hydroxylation in neostriatum due to the inhibitory influence of DA in the extracellular fluid. However, when that influence is absent (e.g., during extended inhibition of DOPA decarboxylation or blockade of DA receptors), stress increases tyrosine hydroxylation via EAAs acting on NMDA and AMPA receptors. Thus, EAAs released from corticostriatal projections may stimulate DA synthesis and thereby restore dopaminergic activity under conditions in which the availability of DA for release has been compromised.