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A Parent

Publications and source records attributed to A Parent.

At least 127 records · Page 7Linked to original sources

Dystrophin-like immunoreactivity in monkey and human brain areas involved in learning and motor functions.

Two antidystrophin antibodies against different fragments of dystrophin were used to detect this polypeptide in monkey and human brains. Dystrophin was revealed by immunoperoxidase amplified with the biotin/avidin system and by immunoblotting. A dystrophin-like immunoreactivity was uniformly expressed in several brain regions implicated in learning and motor functions. Dystrophin function is not clear but our results raise the possibility that this protein may be involved in the cognitive impairment observed in several Duchenne muscular dystrophy (DMD) patients.

Animals↗

Projection from the deep cerebellar nuclei to the pedunculopontine nucleus in the squirrel monkey.

Large injections of the anterograde tracer biocytin in the deep nuclei of the cerebellum of squirrel monkeys (Saimiri sciureus) led to a massive labeling of the superior cerebellar peduncle fibers which could be followed up to their major termination site in the thalamus. Along their course through the brainstem, biocytin-labeled fibers emitted fine collaterals that arborized profusely within the entire rostrocaudal extent of the pedunculopontine nucleus (PPN). These fibers were long, slightly varicose, and broke off into numerous shorter and thinner fibers whose terminal portions consisted of a few large varicosities that were often closely apposed to dendrites and cell bodies of PPN neurons. Some PPN cells that were contacted displayed immunoreactivity for choline acetyltransferase. Ultrastructural analysis revealed that synapses formed by cerebellar fibers in PPN were of the asymmetric type and occurred predominantly on dendrites of PPN neurons. Thus, beside the well established cerebellothalamic projection, our findings reveal the existence of a cerebellotegmental projection, whereby the cerebellum may influence the basal ganglia and/or the thalamus via a relay in PPN.

Animals↗

Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a light and electron microscopic study of the thalamostriatal projection in relation to striatal heterogeneity.

The organization of the thalamostriatal projections arising from the centromedian (CM) and parafascicular (Pf) thalamic nuclei in the squirrel monkey (Saimiri sciureus) was studied at both light and electron microscopic levels. Following selective injections of the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into the CM or Pf, patterns of terminal arborization within the striatum were compared to the biochemical heterogeneity of the striatum as revealed by immunohistochemical staining for the calcium-binding protein calbindin D-28k (CaBP), and histochemical staining for the enzymes acetylcholinesterase (AChE) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-diaphorase). The PHA-L-labeled axon terminals within the striatum were further analyzed at the ultrastructural level to characterize their pattern of synaptic organization. Dense and heterogeneous terminal fields occur in the "sensorimotor" territory of the striatum after CM injections, or in the "associative" striatal territory following Pf injections. In the associative territory labeled axons arborize in a diffuse manner predominantly within areas enriched with CaBP, AChE, or NADPH-diaphorase, representing the matrix compartment, and tend to avoid areas poor in these substances, corresponding to the patch/striosome compartment. In the sensorimotor territory labeled axons form bands that occupy a subregion of the NADPH-diaphorase-rich zone in the putamen. The terminal pattern of the CM-striatal projection suggests the existence of a more complex mosaic organization within the sensorimotor territory. Ultrastructural analysis of PHA-L-labeled elements within the striatum reveals that both CM and Pf projections form asymmetric synapses upon dendrites and spines of striatal cells. A total of 339 PHA-L-labeled boutons were examined after CM injections and compared to 293 boutons following Pf injections. After CM injections, 29% of PHA-L-labeled terminals form synapses on dendritic spines and 66% on dendritic shafts, whereas after Pf injections only 12% of synapses occur on dendritic spines compared to 81% on dendritic shafts. Labeled terminals forming axosomatic or axoaxonic synapses were not seen within the striatum following either CM or Pf injections. It is concluded that in the squirrel monkey: 1) Pf-striatal fibers profusely arborize within the matrix compartment of the associative territory, 2) CM-striatal fibers form bands that occupy a subregion of the NADPH-diaphorase-rich zone within the sensorimotor territory, and 3) that both Pf- and CM-striatal projections establish asymmetric synapses with dendrites and spines of medium-sized spiny cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗

Cortical input to parvalbumin-immunoreactive neurones in the putamen of the squirrel monkey.

The cortex projects heavily to the striatum and makes asymmetrical synaptic contact mainly with the spines of medium-sized densely spiny neurones. The possibility exists that corticostriatal terminals also make synaptic contact with classes of striatal interneurones. The primary objective of the present experiment was to determine whether parvalbumin-immunoreactive neurones, which represent a class of GABAergic interneurones in the striatum, also receive a direct synaptic input from corticostriatal fibres. The anterograde tracer biocytin was injected into the motor and premotor cortices of the squirrel monkey (Saimiri sciureus). Following perfuse-fixation, sections of the striatum were processed histochemically to reveal the transported biocytin using an avidin-biotin-peroxidase complex and diaminobenzidine as the chromogen. They were then immunostained to reveal parvalbumin using benzidine dihydrochloride as the chromogen. In both the light and electron microscopes, the morphological features and the afferent synaptic input of the parvalbumin-immunoreactive neurones were similar to those observed in other species. Similarly, the morphology and postsynaptic targets of the corticostriatal terminals were similar to those described in other species. Light microscopic examination revealed that the anterogradely labelled corticostriatal terminals were often in close apposition to the parvalbumin-positive neurones. At the electron microscopic level the biocytin-positive corticostriatal terminals were found to make asymmetrical synaptic contacts mainly with spines. The parvalbumin-positive neurones were seen to have an invaginated nucleus, extensive cytoplasm and relatively few spines. Parvalbumin-immunoreactive dendrites received a dense synaptic input consisting mainly of asymmetric synapses and only a few symmetric synapses. Biocytin-labelled corticostriatal terminals were often seen in asymmetrical synaptic contact with parvalbumin-immunoreactive dendrites. These results show that GABAergic interneurones identified on the basis of parvalbumin immunoreactivity, in addition to the projection neurones of the striatum, are under the direct influence of the cerebral cortex.

Animals↗

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.

Animals↗

Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a PHA-L study of subcortical projections.

The subcortical projections of the centromedian (CM) and the parafascicular (Pf) thalamic nuclei were examined in the squirrel monkey (Saimiri sciureus) by using the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) as an anterograde tracer. Both CM and Pf project massively to the striatum where they arborize in a complementary fashion. On the one hand, CM innervates most of the putamen caudal to the anterior commissure, a dorsolateral rim of the putamen rostral to the anterior commissure, discrete areas of the head of the caudate nucleus close to the internal capsule, and a lateral sector of the body of the caudate nucleus. On the other hand, Pf provides a heavy input to the head, body, and tail of the caudate nucleus, and to the rostral putamen, excluding the areas innervated by CM. In addition, Pf projects more discretely to the nucleus accumbens and the olfactory tubercle. Therefore, the projections from both CM and Pf cover the entire striatum, with those from CM arborizing into the "sensorimotor" striatal territory and the ones from Pf innervating the "associative-limbic" striatal territory. Furthermore, CM and Pf project to extrastriatal subcortical structures, such as the globus pallidus, the subthalamic nucleus, and the substantia nigra, where they also terminate in a complementary fashion. Topographically and cytologically, Pf is closely related to the subparafascicular nucleus (sPf). The Pf-sPf complex projects to the hypothalamus, the substantia innominata, the peripeduncular nucleus, and the amygdala. It also gives rise to descending efferents arborizing in various brainstem structures, including the inferior olivary complex. Additional studies with retrograde double-labeling methods show that distinct cell groups within CM project to the motor cortex and the striatum. Likewise, separate neuronal populations within the CM-Pf-sPf complex give rise to striatal and brainstem projections, the former arising from CM and Pf and the latter mainly from sPf. The complementary nature of CM and Pf projections to the striatum and other basal ganglia components suggests that this thalamic complex participates in a highly ordered manner in the parallel processing of the information that flows through the basal ganglia.

Afferent Pathways↗

Distribution of somatostatin immunoreactivity in the forebrain of the squirrel monkey: basal ganglia and amygdala.

The distribution of somatostatin immunoreactivity in the basal ganglia and amygdala of the squirrel monkey (Saimiri sciureus) was studied with specific polyclonal antibodies directed against somatostatin-28 and somatostatin-28(1-12). Both antibodies gave similar results with regard to the distribution of somatostatin-immunoreactive neuronal profiles. A moderately dense and highly heterogeneous network of somatostatin-positive fibers was observed throughout the striatum. A dorsoventral gradient of increasing immunoreactivity was noted in the striatum and the caudate nucleus was found to strain generally less intensely than the putamen. The immunoreactive fibers within the striatum were mostly thin and varicose and formed patches corresponding to the striosomes, as visualized on adjacent sections immunostained for calbindin. Although some somatostatin cell bodies rimmed the striosomes, most of the positive cells were rather uniformly scattered in the striatum. These medium-sized cells were significantly smaller in the caudate nucleus (93 microns2, S.D. = 26 microns2) than in the putamen (122 microns2, S.D. = 39 microns2), but their density was significantly higher in the caudate nucleus (29.7 cells/mm2, S.D. = 8.8 cells/mm2) than in the putamen (20.5 cells/mm2, S.D. = 7.0 cells/mm2). The nucleus accumbens stained moderately and positive cell bodies were evenly dispersed throughout this structure. In contrast, the olfactory tubercle displayed a heavily stained neuropil but positive neurons were encountered only in its polymorph layer. In the sublenticular region, dense fiber plexuses appeared in register with nonreactive cell clusters of the nucleus basalis of Meynert and of the nucleus of the anterior commissure. More caudally, a dense bundle of positive fibers was observed at the level of the ansa lenticularis, the inferior thalamic peduncle, and the adjoining bed nucleus of the stria terminalis. Several fibers contributing to this bundle were of the woolly type. Woolly fibers also coursed in the substantia innominata between the ventral aspect of the globus pallidus and the optic tract, and ascended in the internal medullary lamina separating the internal and external segments of the globus pallidus. Somatostatin-immunoreactive cell bodies were uniformly scattered throughout the substantia innominata. The various nuclei of the amygdala showed a wide range of immunoreactivity. The central nucleus was lightly reactive, whereas the intercalated masses displayed a moderate staining. A dorsoventral gradient of immunostaining was noted in the ventrolateral portion of the amygdala, the lateral nucleus being moderately to densely stained and the basal nucleus very lightly to lightly immunoreactive.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗

Vascular atrial natriuretic factor receptors in spontaneously hypertensive rats.

OBJECTIVE: The aim was to investigate vascular receptors for atrial natriuretic factor (ANF) in spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats (WR) at different ages. METHODS: Relaxation and guanylate cyclase responses of blood vessels to atrial natriuretic factor were investigated, as was the binding of 125I-ANF to vascular membranes and ANF receptor subtypes, using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) in reducing conditions, after solubilisation and irreversible binding of 125I-ANF. RESULTS: Vascular relaxation responses of aorta showed an increased sensitivity to ANF in four week old SHR [pD2 = 8.9 (SEM 0.1) v 8.5(0.1) in WKY rats, p < 0.05] while sensitivity was similar for the three strains at older ages. Production of cyclic GMP in mesenteric arteries in response to 100 nmol.litre-1 ANF was greater (p < 0.05) in SHR than in WKY rats at four weeks of age, but was similar in older rats. The density of binding sites for ANF in mesenteric arteries, however, was lower in SHR at four weeks (p < 0.01), and increased in older rats, becoming similar to that of normotensive rats at 12 weeks of age. Affinity of ANF sites was similar in all strains. The proportion of high and low molecular weight ANF binding peptides in solubilised blood vessel membranes on SDS-PAGE was similar in all strains except in four week old SHR, in which binding to the high molecular weight band (presumably the guanylate cyclase containing receptor) was increased relative to the low molecular weight band (non-cyclase-coupled receptor) in comparison to other strains and ages. CONCLUSIONS: Activity of guanylate cyclase in response to occupancy of ANF receptors may be increased in young SHR. Normal relaxation of blood vessels in response to ANF in older SHR could result in failure to counteract the increased vasoconstrictor activity present in these rats, which could play a role in the increase in blood pressure.

Animals↗

Inositol phosphate production in response to [Arg8]vasopressin, endothelin 1, and prostaglandin F2 alpha in rat aorta and mesenteric arteries.

Vascular tissues such as rat aorta and mesenteric arteries are extensively used experimentally for the study of cardiovascular diseases. To further our understanding of the signal transduction mechanisms involved in responses to several potent vasoconstrictors, such as [Arg8]vasopressin (AVP), endothelin 1 (ET-1), and prostaglandin F2 alpha (PGF2 alpha), we have investigated the time course for production of inositol monophosphate (InsP1), bisphosphate (InsP2), and trisphosphate (InsP3) in response to these agonists as well as their relative potency for phosphatidylinositol hydrolysis. Time-course studies of production of the different inositol phosphates in response to AVP and PGF2 alpha showed an early increase after 15-30 s of stimulation. Thereafter InsP3 declined towards baseline, with a secondary increase towards steady state after 5-10 min. Rapid turnover of InsP3 was reflected by accumulation of InsP1 and InsP2 in the presence of LiCl (20 mM) to inhibit monophosphatases. After 15-30 min of stimulation, there was accumulation of the Ins(1,3,4)P3 isomer. All three agonists induced greater accumulation of InsP2 in mesenteric arteries than in thoracic aorta, suggesting that turnover of Ins(1,4,5)P3 may be faster in the former than in the latter. The accumulation of total inositol phosphates induced by maximum concentrations of ET-1 was greater than in response to AVP or PGF2 alpha. Dose-response curves showed that the rank order of potency for stimulation of production of inositol phosphates was AVP > ET-1 > PGF2 alpha, similar to the sensitivity of blood vessels to these agents. Comparison of responses to ET-1 and ET-3 showed that the receptors stimulated by endothelins were of the isopeptide selective ETA subtype.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Endothelin vascular receptors and responses in deoxycorticosterone acetate-salt hypertensive rats.

The vasoconstrictor effect, the binding, and the response of inositol phosphates to endothelin-1 (ET-1) were investigated in blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats within 2 weeks of development of hypertension and in uninephrectomized control rats. In DOCA-salt and uninephrectomized rats, plasma levels of endothelin were similar (1.2 +/- 0.1 fmol/ml). Thoracic aorta and mesenteric artery rings devoid of endothelium presented significantly decreased responses to increasing concentrations of ET-1. Binding of ET-1 to mesenteric artery membranes was significantly lower in DOCA-salt rats (106 +/- 22 fmol/mg protein) than in uninephrectomized rats (172 +/- 19 fmol/mg protein, p less than 0.05), whereas affinity was similar. Phosphoinositide metabolism was examined in aorta and mesenteric arteries after incubation with [3H]myoinositol. Inositol phosphates were separated by high-performance liquid chromatography. In response to 100 nmol/l ET-1, accumulation of inositol 1,4,5-trisphosphate after 20 seconds and of inositol monophosphate, inositol bisphosphate, and inositol 1,3,4-triphosphate after 30 minutes (in the presence of 25 mmol/l LiCl) were significantly lower in DOCA-salt hypertensive than in uninephrectomized control rats, in both aorta and mesenteric arteries. In conclusion, decreased density of ET-1 receptors in DOCA-salt hypertensive rats results in decreased activation of phospholipase C and, consequently, reduced vasoconstriction induced by ET-1. Because the decrease in vasoconstrictor effects of ET-1 is found in the absence of endothelium, it is likely that receptor downregulation rather than prior receptor occupancy underlies these findings.

Animals↗

Contralateral pallidothalamic and pallidotegmental projections in primates: an anterograde and retrograde labeling study.

Unilateral injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in the internal segment of the pallidum (GPi) of the squirrel monkey (Saimiri sciureus) led to anterograde labeling of fibers ipsilaterally in the following thalamic nuclei: ventral anterior (VA), ventral lateral (VL), centromedian (CM), and lateral habenula (Hbl). The labeled fibers reached these ipsilateral thalamic nuclei by coursing along or through the ansa lenticularis, the lenticular and thalamic fasciculi, and the Forel's fields. They arborized profusely in VA/VL nuclei where they displayed small glomerule-like formations. Numerous labeled fibers also occurred in the CM. Most of them were long, varicose and gave rise to shorter fibers that formed a dense terminal field covering a large portion of the CM. A small but dense terminal field composed of delicate fibers and extremely fine terminals was noted in the Hbl. A large contingent of labeled fibers were seen to cross the midline, principally at the rostral pole of the CM and in the supramammillary decussation, to reach the contralateral thalamus where they arborized profusely in the VA/VL and CM nuclei, but not in the Hbl. The patterns of termination of these contralateral pallidothalamic fibers were strikingly similar to those observed ipsilaterally. Other anterogradely labeled fibers were also noted bilaterally in the pedunculopontine nucleus (TPP) and ipsilaterally in the external segment of the pallidum (GPe) and in the putamen. Complementary, double-labeling, retrograde studies involving the injection of nuclear yellow in the VA/VL and CM nuclei and Fast blue in the TPP, confirmed the existence of contralateral pallidothalamic and pallidotegmental projections. The number of retrogradely labeled cells in the contralateral GPi amounted approximately to 10-20% that in the ipsilateral GPi. These experiments further indicated that contralaterally projecting pallidothalamic neurons exhibited a high degree of axonal collateralization, the majority of its neurons projecting also to the contralateral TPP. Cells retrogradely labeled with the tracer injected into the thalamus were also encountered bilaterally in the thalamic reticular nucleus. Taken together, the results of these anterograde and retrograde investigations indicate that the contralateral pallidothalamic projection involves a relatively small population of GPi neurons, but that these neurons arborize extensively in their contralateral thalamic targets. Furthermore, the presence of retrogradely labeled cells in the ipsi- and contralateral reticular thalamic nucleus indicates that the VA/VL and CM nuclei, which receive a massive input from the GPi, are under the bilateral influence of this perithalamic nucleus. Such contralateral projections could play a major role in the subcortical organization of the bilateral aspect of normal basal ganglia function.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Serotoninergic innervation of the thalamus in the primate: an immunohistochemical study.

Little is known of the serotoninergic innervation of the thalamus in primates; therefore, we undertook a detailed study of the distribution of 5-hydroxytryptamine (5-HT)-immunoreactive neuronal profiles in the thalamus of the squirrel monkey (Saimiri sciureus) with a specific antibody directly raised against 5-HT. All thalamic nuclei in the squirrel monkey displayed 5-HT-immunoreactive fibers, but none contained immunopositive cell bodies. The 5-HT innervation of the thalamus derived from extrinsic fibers arising mostly from the midbrain raphe nuclei and forming the transtegmental system. Most of the fibers destined to the thalamus collected into a major bundle that swept dorsoventrally within the midbrain tegmentum and coursed beneath the thalamus along its entire caudorostral extent. Several fiber fascicles broke off from this main bundle at different levels and ascended dorsally to innervate the various thalamic nuclei. Overall, the 5-HT innervation of the thalamus in the squirrel monkey was more massive than would have been expected from earlier studies in nonprimate species. Marked differences in the regional density of innervation were noted both between the various nuclei and within single nuclei. The most densely innervated nuclei were those delineating the principal subdivisions of the thalamic mass, that is, the midline, rostral intralaminar, limitans, and reticular nuclei, where very dense fields of isolated axonal varicosities occurred. In contrast to the rostral intralaminar nuclei, which were rather uniformly innervated, the centre médian/parafascicular complex contained immunoreactive fibers and isolated varicosities distributed according to a mediolateral gradient. The habenula and the ventral anterior nucleus were among the most weakly innervated nuclei. In the latter nucleus, as well as in more densely innervated nuclei, thin varicose fibers formed numerous pericellular contacts on cell bodies and proximal dendrites of thalamic neurons. The 5-HT innervation of the lateral nuclear group as well as that of the medial and lateral geniculate nuclei ranged from very weak to dense. The mediodorsal nucleus displayed a highly heterogeneous 5-HT innervation that varied from weak in its central portion to moderate or dense in its medial and lateral borders. A moderate 5-HT innervation was observed in the anterior nuclear group. The surprisingly dense and heterogeneous 5-HT innervation of the thalamus noted in the present study suggests that serotonin may be involved in several specific functions of the thalamus in primates.

Animals↗

Projection from the external pallidum to the reticular thalamic nucleus in the squirrel monkey.

Small injections of biocytin in the external segment of the pallidum (GPe) of the squirrel monkey (Saimiri sciureus) led to anterograde labeling of fibers in the thalamic reticular nucleus (NRT). These fibers reached NRT by coursing along the ventral tip of the internal capsule or by directly piercing the internal capsule more dorsally. They arborized profusely within the entire rostrocaudal extent of the nucleus. Within NRT, biocytin-labeled fibers were long, slightly varicosed, and emitted numerous short collaterals whose terminal portions consisted of clusters of large varicosities. Some of these varicosities were closely apposed to cell bodies and proximal dendrites of NRT neurons. Small injections of wheat germ-agglutinated horseradish peroxidase in the rostral pole of NRT led to retrograde cell labeling within the entire rostrocaudal extent of GPe. These retrogradely-labeled cells did not display immunoreactivity for choline acetyltransferase. Hence, beside the well-established projection from the internal pallidum to the thalamus, our findings support the existence of another pallidothalamic projection whereby GPe neurons could exert a powerful influence upon the thalamocortical neurons via a relay in NRT.

Animals↗

Topography of the projection from the central complex of the thalamus to the sensorimotor striatal territory in monkeys.

The distribution of axons arising from the central complex (or centre médian-parafascicular complex) and terminating in the striatum was studied in seven macaques and one squirrel monkey. Deposits of anterograde tracers were made in the two lateral-most subdivisions of the central complex, i.e., the middle part (or pars media) and the lateral part (or pars paralateralis). All injections avoided the pars parafascicularis. The intrastriatal distribution of labeled axonal endings was mapped in relation to the standard ventricular (CA-CP) system of coordinates. Labeled endings were observed in the major posterior and dorsal parts of the putamen (excluding its anteromedial and ventral parts) and also in a restricted ventrolateral part of the caudate nucleus. The topography of the central territory of the striatum, defined as the striatal space receiving axons from the central complex, was found to correspond exactly to that of the cortical sensorimotor territory delineated after cortical injections. The termination pattern of the central axons within the striatum was patchy. Viewed as a whole, the irregular and hazy patches formed oblique streaks, parallel one with the other. The three-dimensional reconstructions of data from transverse sections revealed that the streaks were bi-dimensional pictures of three-dimensional parasagittal layers covering the whole anteroposterior extent of the cortical sensorimotor territory of the striatum. Our work shows that the pars media of the central complex, which receives selectively pallidal afferent axons (François et al., '88: Brain Res. 473:181-186), is the main source of the centroputaminal projection. The probable implication of this in a closed sensorimotor loop of the basal ganglia is discussed.

Animals↗

Effects of dopamine denervation on striatal peptide expression in parkinsonian monkeys.

In cynomolgus monkeys rendered parkinsonian by systemic injection of MPTP, severe cell losses were noted in the ventrolateral portion of the substantia nigra pars compacta (SNc), compared to a relative sparing of neurons in the ventral tegmental area (VTA) and dorsomedial portion of SNc. Most spared neurons in the SNc-VTA complex were found to contain the calcium binding protein calbindin (CaBP). At striatal levels the dopaminergic (DA) innervation, as visualized by tyrosine hydroxylase immunoreactivity, was markedly reduced in the 'sensorimotor' territory, variably affected in the 'associative' territory, and relatively well preserved in the 'limbic' territory. The immunoreactivity for enkephalin was enhanced and that for substance P was decreased in the sensorimotor territory, whereas the inverse was observed in the limbic territory. The distribution of the two peptides was highly heterogeneous in the associative territory. These findings suggest that the influence of the DA input on peptide expression varies from one striatal territory to the other, and that CaBP may protect midbrain DA neurons from MPTP toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Dopaminergic neurons expressing calbindin in normal and parkinsonian monkeys.

In cynomolgus monkeys, midbrain neurons immunoreactive (IR) for the calcium-binding protein calbindin D-28k (CaBP) occur principally in the dorsal tier of substantia nigra pars compacta (SNc) and in the ventral tegmental area (VTA), and most of these neurons co-express tyrosine hydroxylase (TH). In monkeys rendered parkinsonian (PD) after MPTP injections, CaBP-IR neurons are much less severely affected than TH-IR neurons in SNc and in VTA, and most spared neurons in SNc/VTA display both CaBP and TH immunoreactivity. These results reveal that, in contrast to the situation in other neurodegenerative diseases, CaBP may be used as a marker for a specific neuronal population that is less prone to degeneration in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗