PubMed Health⌕ Search

Biomedical subjects

L Descarries

Publications and source records attributed to L Descarries.

At least 73 records · Page 4Linked to original sources

Noradrenaline axon terminals in adult rat neocortex: an immunocytochemical analysis in serial thin sections.

Peroxidase-antiperoxidase electron microscope immunocytochemistry with an antiserum against noradrenaline-glutaraldehyde-protein conjugate was used to identify cortical noradrenaline terminals (axonal varicosities) from the upper layers of the frontal, parietal and occipital cortex in adult rat. A large number of immunostained varicosities were examined in serial thin sections, and compared with a control population of randomly chosen unlabeled terminals from the same sections. Both groups of varicosities were measured and scrutinized for the presence of a junctional complex indicative of synaptic specialization. Cellular elements juxtaposed to the membrane of both types of varicosities were also identified and counted. Noradrenaline varicosities in all three cortical regions averaged 0.65 microns in diameter. In contrast to their unlabeled counterparts, these profiles rarely showed a membrane differentiation characteristic of a synaptic contact (junctional complex). The rare junctional complexes formed by cortical noradrenaline varicosities were invariably symmetrical and almost always found on dendritic shafts. The microenvironment of noradrenaline varicosities also differed, exhibiting a greater number of apposed axonal varicosities and a smaller number of dendritic spines than that of the random population. The proportion of noradrenaline varicosities making a synaptic contact (synaptic incidence) was determined by plotting the incidence of visible junctions as a function of the number of thin sections available for examination. As extrapolated for whole varicosities after linear transformation (double reciprocal plot), this proportion was 17% or 26% depending on the stringency of the criteria used in identifying the junctional complex. The same analysis provided a figure of 98% for the control population. The present study largely confirmed our initial radioautographic characterization of the cortical noradrenaline innervation as a mostly non-junctional system, and also indicated that these varicosities are set in a particular microenvironment. These new data further support the eventuality of a diffuse release of cortical noradrenaline in the extracellular space, compatible with both its neuromodulatory role and multiplicity of actions on diverse cellular targets in the cerebral cortex. The functions assigned to the coeruleocortical noradrenaline system must therefore be viewed as the product of a widespread and ubiquitously distributed neuronal organization characterized by loose intercellular relationships. This system might be capable of selectivity and specificity of action, however, owing to the distribution of its receptors, and in view of intrinsically or extrinsically driven control mechanisms triggered by the release of its own or other transmitters and which may also involve target-initiated feedback mechanisms.

Animals↗

Quantified distribution of the serotonin innervation in adult rat hippocampus.

To quantify the serotonin innervation in adult rat hippocampus, serotonin axon terminals (varicosities) were uptake-labeled for light microscope radioautography in whole hemisphere slices incubated with 1 microM [3H]serotonin. The labeled varicosities were visualized as small aggregates of silver grains and counted with the aid of an image analysis system across all layers in representative sectors of subiculum, Ammon's horn (CA1, CA3-a, CA3-b) and dentate gyrus (medial blade, crest and lateral blade). Counts were obtained in six rats at three equidistant horizontal levels from the ventral two-thirds of the hippocampus. After double correction for duration of radioautographic exposure and section thickness, and measurement of the mean diameter of labeled varicosities in electron microscope radioautographs, the results were expressed in number of varicosities per mm3 of tissue. The overall density of hippocampal serotonin innervation was thus evaluated at 2.7 x 10(6) varicosities per mm3, and appeared significantly higher in subiculum (3.6 x 10(6)) and Ammon's horn (3.1 x 10(6)) than in dentate gyrus (2.2 x 10(6)). Subiculum and dentate gyrus-crest (2.0 x 10(6)) had the highest and lowest regional densities. There was a marked heterogeneity also in terms of laminar distribution. For example, the stratum moleculare of subiculum and CA1, and the stratum oriens of CA3 (5.2 x 10(6)) varicosities in CA3-a), showed much higher values than the pyramidal cell layer (0.7, 1.1 and 0.7 x 10(6) in CA1, CA3-a and CA3-b, respectively). Similarly, the granular layer of dentate gyrus had a much lower density (1.1 x 10(6)) than did the molecular (2.8 x 10(6)) and the polymorph layer (2.4 x 10(6)). From these data, it was possible to evaluate the mean endogenous amine content per hippocampal serotonin varicosity (0.05-0.07 fg), and the average number of serotonin varicosities per hippocampal neuron in both CA3 (130) and dentate gyrus (20-35). In the context of current data on the distribution of serotonin receptors and diverse actions of serotonin at the cellular level in hippocampus, such quantified information provides new insights on some basic properties of serotonin in this part of the brain.

Animals↗

Ultrastructural relationships of serotonin axon terminals in the cerebral cortex of the adult rat.

PAP immunocytochemistry with an antiserum against serotonin (5-HT)-glutaraldehyde-protein conjugate (kindly donated by M. Geffard) was used to analyze the ultrastructural relationships of 5-HT axon terminals (varicosities) in the frontal (Fr1-Fr2), parietal (Par1), and occipital (Oc1M-Oc2) cortex of adult rats. One hundred-forty-five immunostained varicosities from Fr1-Fr2 (54 from layers I-II; 91 from layer VI) and 97 each from the upper layers (I-II) of Par1 and OcM1-Oc2 were examined in groups of serial thin sections (mean number of sections in series: 3.2 to 7.3). These terminals were of comparable shape and size in the 4 cortical sectors examined, and averaged 0.66 +/- 0.2 microns in mean diameter. The proportion of varicosities engaged in synaptic contact was evaluated by linear transformation of the relationship between the frequency of observed synaptic junctions and the number of thin sections available for examination. Reliability of the sampling was evidenced by a high coefficient of correlation (r greater than 0.95) in each cortical sector. The synaptic incidence extrapolated for whole varicosities ranged from 28% (layer VI of Fr1-Fr2) to 46% (Par1), without statistically significant differences between the 4 sectors examined. The interregional mean could thus be evaluated at 38%. The synaptic 5-HT terminals always made asymmetrical junctions, which were exclusively found on dendritic spines and shafts, and appeared more frequent on spines than shafts in the deep frontal and the upper occipital cortex. In all 4 sectors, dendritic shafts and spines and other axonal varicosities were frequently encountered in the immediate microenvironment of the immunostained varicosities. It is concluded that the cortical 5-HT innervation is predominantly nonjunctional throughout the neocortex of the adult rat, which reinforces earlier views of a highly divergent afferent system with particular functional properties and perhaps capable of widespread, global and/or sustained influences in this part of the brain.

Animals↗

Possible existence of a presynaptic positive feedback mechanism enhancing dopamine transmission in the anterior cingulate cortex of the rat.

A series of microiontophoretic and VTA stimulation experiments, conducted in intact, GBR-12909-treated, alpha-methylparatyrosine-depleted or 6-hydroxydopamine-denervated rats, provide suggestive evidence for the existence of a presynaptic, positive feedback mechanism triggered by dopamine reuptake and favoring the release of this transmitter in the anterior cingulate cortex.

Animals↗

Serotonin innervation in adult rat neostriatum. II. Ultrastructural features: a radioautographic and immunocytochemical study.

High-resolution radioautography after cerebroventricular administration of tritiated serotonin (5-HT) and PAP immunocytochemistry with an antiserum against 5-HT-glutaraldehyde conjugate (kindly donated by M. Geffard) were used in parallel to investigate the intrinsic and relational fine structural features of 5-HT axon varicosities (terminals) in the neostriatum of the adult rat. The uptake-labeled varicosities were examined in single thin sections from a paraventricular sector of neostriatum, whereas their immunostained counterparts were viewed in serial thin sections from the same paraventricular sector plus a dorsal neostriatal sector. The two approaches yielded complementary results in terms of varicosity dimensions, synaptic features and appositional relationships. Serotonin axon terminals were generally small and, as measured in immunostained material, even smaller in the dorsal than in the paraventricular neostriatum. Their internal features, best viewed in radioautographs, included small pleomorphic synaptic vesicles with occasional large granular vesicles and mitochondria. Junctional 5-HT terminals from both the paraventricular and the dorsal neostriatal sectors synapsed exclusively, and with equal frequency, on dendritic spines or shafts, almost always with asymmetrical membrane differentiations. The proportion of junctional varicosities, however, was very low in serial (immunocytochemical) as well as single (radioautographic) thin sections. Only 10-13% of 5-HT varicosities from either the paraventricular or the dorsal neostriatum exhibited a synaptic junction, in contrast with a junctional incidence of at least 70% for randomly selected axonal varicosities similarly sampled in the surrounding neuropil. Serotonin axon terminals, whether or not synaptic, were closely apposed to a variety of structures comprising mostly other axon terminals, dendritic spines and branches, but rarely neuronal somata. The synaptic and appositional features of immunostained 5-HT varicosities were similar for both the dorsal and the paraventricular neostriatum. In this context, it is likely that the effects of 5-HT in the neostriatum are exerted upon a multiplicity of cellular target sites in addition to the restricted number of dendritic spines and shafts synaptically contacted by this type of monoamine terminal.

Animals↗

Quantified distribution of the noradrenaline innervation in the hippocampus of adult rat.

A recently developed radioautographic technique, based on the uptake labeling of monoamine terminals (axonal varicosities) in vitro, was used to quantify the noradrenaline (NA) innervation in adult rat hippocampus. After incubation of brain slices with 1 microM 3H-NA, the NA varicosities were visualized as small aggregates of silver grains, in light microscope radioautographs prepared at 3 equidistant horizontal levels across the ventral 2/3 of the hippocampus. Using a computer-assisted image analyzer, counts were obtained from the subiculum (SUB), 3 sectors of Ammon's horn (CA1, CA3-a, CA3-b) and 3 sectors of the dentate gyrus (DG-medial blade, crest, and lateral blade), every lamina being sampled in each region. After a double correction for duration of radioautographic exposure and section thickness, and following measurement of varicosity diameter in electron microscope radioautographs, it was possible to express these results in number of terminals per volumetric unit of tissue. It was thus found that the overall density of hippocampal NA innervation averages 2.1 million varicosities/mm3 of tissue, a value almost twice as high as that in cerebral cortex. This innervation is 20% denser ventrally than dorsally and is heterogeneous both in terms of regional and laminar distribution. SUB and DG are more strongly innervated than Ammon's horn, wherein CA1 has the lowest overall density. In SUB and CA1, there is a clear predilection of NA varicosities for the stratum moleculare. In CA3, there is a narrow band of even stronger innervation in the stratum radiatum, near the apical border of the stratum pyramidale, contrasting with a 3 times lower density in this cell layer and the stratum oriens. In DG, the NA innervation is again the weakest in the cell body layer (granule) and exhibits an almost 3-fold greater density in the polymorph layer, the highest of all hippocampus. These figures allow for numerous correlations with other quantitative parameters--cytological, biochemical, and pharmacological--of NA function in the hippocampus. They also provide a strong basis for elucidating, at a cellular level, the action of NA in this part of the brain.

Animals↗

Quantified regional and laminar distribution of the noradrenaline innervation in the anterior half of the adult rat cerebral cortex.

The regional and laminar distribution of the noradrenaline (NA) innervation in the adult rat cerebral cortex was quantified in radioautographs of semithin sections from whole hemisphere slices incubated with tritiated catecholamines and a monoamine oxidase inhibitor. Uptake-labeled axonal varicosities (aggregates of silver grains) were counted with the help of a computerized image analyzer in seven cytoarchitectonic areas of the rostral half of the cortex: Cg3, rostral AID, Cg2, Fr1, Par1, caudal AID, and Pir (prepiriform) according to Zilles's nomenclature. Both dopamine (DA) and NA terminals were detected after incubation with [3H]DA and citalopram or with [3H]NA alone. In the presence of desipramine (DMI), DA terminals alone were demonstrated; the number of NA terminals was then obtained by subtraction from counts in adjacent slices incubated with or without DMI. These counts suggested that DA and NA varicosities were fully visualized only after labeling with their respective tritiated amine. Similar numbers of labeled NA varicosities as inferred after [3H]NA incubation with or without DMI were observed after [3H]NA incubation in the presence of benztropine (BZ). This indicated that NA terminals were then maximally detected to the exclusion of the DA ones, and the latter approach was adopted for the acquisition of normative data. Since the average diameter of the labeled NA varicosities was known from earlier measurements in electron microscope radioautographs, the initial counts of labeled sites/mm2 of histological section could be expressed as numbers of varicosities/mm3 of tissue following a double correction for incomplete detection at the chosen duration of radioautographic exposure and section thickness. The overall density of NA innervation was thus estimated at 1.2 million varicosities/mm3 of tissue, with no statistically significant differences between the seven cortical areas examined. In every region, the number of NA terminals was the greatest in the molecular layer (1.5-2 times the density in the rest of cortex) and then progressively decreased in the underlying cortex, with a two- to threefold difference between upper and lower layers. These numerical data allowed an estimation to be made of the possible number of cortical NA varicosities per locus coeruleus nerve cell body of origin (at least 300,000), of their average number per cortical neuron (30-50), their actual incidence among all terminals in the cortex (1/1,000), their mean endogenous amine content per varicosity (0.22 fg), and the mean number of recognition sites for the uptake blocker DMI (4,500/varicosity).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Monoamine innervation of the organum vasculosum laminae terminalis (OVLT): a high resolution radioautographic study in the rat.

The monoamine innervation of the organum vasculosum laminae terminalis (OVLT) was examined in the adult rat by light and electron microscope radioautography after intraventricular administration of tritiated serotonin [( 3H]5-HT) or dopamine [( 3H]DA). Radioautographic and biochemical controls after 5,7-dihydroxytryptamine or 6-hydroxydopamine lesioning established the respective serotonin (5-HT) and catecholamine (CA) identities of the axonal varicosities labeled under the conditions of the present experiments. For descriptive purposes, the OVLT was subdivided in three parts: two parenchymal zones, one juxtaventricular, the other juxtavascular, and the vascular core. Almost 10% of all axonal varicosities in the OVLT were found to be labeled with [3H]5-HT. This 5-HT innervation was most prominent in the rostrocaudal and ventrodorsal portions of the juxtaventricular zone and the dorsal aspect of the juxtavascular zone; there was none in the vascular core. [3H]DA-labeled varicosities were much less abundant and yet more numerous than earlier histofluorescent and immunohistochemical studies would have predicted. They predominated in the juxtavascular zone, where a majority presumably had a dopamine (DA) rather than a noradrenaline identity. Some were also found in the vascular core, where they most likely corresponded to peripheral autonomic noradrenaline endings. In the juxtaventricular zone of the OVLT, a significant proportion of the [3H]5-HT-labeled varicosity profiles could be observed to form axodendritic synapses, but in the juxtavascular zone no 5-HT or any [3H]DA-labeled ones were ever seen in synaptic junction. In the juxtavascular zone, the 5-HT and the presumed DA endings established close relationships with neurosecretory axons, and with astrocytic or tanycytic processes on which they occasionally formed "synaptoid contacts." A few endings of either type were also seen to about directly on the outer basement membrane of the perivascular space. It therefore appears probable that in OVLT monoamines influence neural and nonneural elements. At a proximal level of regulation (juxtaventricular zone), 5-HT could act both synaptically and nonsynaptically as an interneuronal transmitter or modulator. In contrast, distally (juxtavascular zone), both DA and 5-HT could be released as neurohormones in addition to modulating neurosecretion. 5-HT and DA varicosities in the OVLT could also behave as sensors for circulating factors that do not cross the blood-brain barrier.

Animals↗

Ultrastructural features of dopamine axon terminals in the anteromedial and the suprarhinal cortex of adult rat.

The ultrastructural features and synaptic relationships of dopamine (DA) axon terminals were examined in the prefrontal cortex of adult rat after immunocytochemical staining with a highly specific polyclonal antiserum directed against DA-glutaraldehyde-lysyl-protein conjugate (donated by M. Geffard). Single and serial ultrathin sections were obtained from the deep layers of the anteromedial and the suprarhinal DA fields. The DA axon terminals from both regions averaged 0.7 micron in diameter, contained a mixed population of small, round and clear synaptic vesicles associated with a few larger dense-cored or fully immunostained vesicles, and frequently exhibited synaptic contacts which were exclusively made on dendritic shafts and spines. These synapses were mostly of the symmetrical type (80%) and were more often seen on dendritic shafts than spines, particularly in the suprarhinal (89%) compared with the anteromedial cortex (62%). As estimated either by stereological extrapolation from single sections or by direct observation in serial sections, the synaptic incidence of these DA varicosities was significantly greater in the anteromedial than suprarhinal DA field. In the longest series of thin sections, a junctional complex could be observed on 93% of the DA varicosities from the anteromedial cortex but only on 56% in the suprarhinal cortex. Such an inter-regional disparity in the relational characteristics of the DA input will need to be taken into account in elucidating the role and properties of this monoamine in cerebral cortex.

Animals↗

Radioautographic method for quantifying regional monoamine innervations in the rat brain. Application to the cerebral cortex.

Conditions leading to selective and complete labeling of the noradrenaline (NA) and serotonin (5-HT) innervations in rat cerebral cortex were sought by incubating 200-micron-thick whole hemisphere slices with various combinations of tritiated monoamines and uptake blockers at different concentrations in the presence of a monoamine oxidase inhibitor. After fixation with glutaraldehyde, post-fixation with osmium tetroxide and flat-embedding in Epon, 4-micron-thick sections of the entire slices were radioautographed by dipping in nuclear emulsion. As previously reported, dopamine (DA) terminals could be specifically visualized and counted following incubation with 1 micron [3H]DA and 5 microM desipramine (DMI) with or without 5 microM citalopram (CITAL). The number of NA terminals could thus be obtained by subtracting DA varicosities from the total number of sites labeled in adjacent slices incubated without DMI but in presence of CITAL to eliminate some interspecific labeling of 5-HT terminals. NA terminals could also be identified exclusively and counted after labeling with 1 microM [3H]NA in the presence of 10 microM benztropine. 5-HT terminals were specifically detected after incubation with 1 microM [3H]5-HT in the presence of 10 microM non-radioactive NA. The labeled varicosities were counted in areas FR1 and PAR1 of the frontal and the parietal neocortex, respectively, with the aid of a microcomputer-based image analysis system. DA varicosities were concentrated mainly in layer VI of these regions and were more numerous in the frontal than the parietal area. NA terminals were equally distributed in the two regions but approximately twice as numerous in layer I than subjacent layers. The 5-HT innervation also showed a comparable overall density in the two cortical regions but with a differing intracortical distribution. In the frontal area, 5-HT terminals were slightly more concentrated in layer I (1.3-fold) than underlying layers where they were rather uniformly distributed. In the parietal area, layer I was again the most densely innervated (1.8 times the average), but a second zone of higher density (1.5 times average) was present in the outer part of layer V. The remaining layers showed lower numbers of 5-HT terminals than in the frontal region. To obtain absolute estimates of these innervation densities, the number of detected varicosities was assessed experimentally as a function of radioautographic exposure time and of histological section thickness, and their 'equivalent circle diameter' was measured in electron microscope radioautographs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Density of the dopamine innervation in rat cerebral cortex after neonatal 6-hydroxydopamine or adult stage DSP-4 noradrenaline denervations: a quantitative radioautographic study.

An in vitro radioautographic approach was used to count dopamine axon terminals (varicosities) of the mediofrontal and the supragenual cingulate cortex in 30-40-day-old rats treated with 6-hydroxydopamine at birth or with N(2-chloro-ethyl)N-ethyl-2-bromobenzylamine hydrochloride (DSP-4) 7-10 days earlier. Compared to controls, there were no increases in the density of dopamine innervation in either region of the noradrenaline-denervated cortex after either treatment. The results, therefore, did not support the hypothesis of a sprouting of dopamine terminals reported to account for augmented cortical dopamine levels under these conditions. In line with earlier observations, such biochemical changes might rather be indicative of altered dopamine steady-state levels.

Animals↗

Distribution and morphological characteristics of dopamine-immunoreactive neurons in the midbrain of the squirrel monkey (Saimiri sciureus).

The distribution and morphological characteristics of dopamine (DA) neurons in the midbrain of the squirrel monkey (Saimiri sciureus) were investigated by peroxidase-antiperoxidase (PAP) immunohistochemistry with a highly specific antiserum raised against DA-glutaraldehyde-lysyl-protein conjugate (donated by M. Geffard). Four contiguous areas contained DA-immunostained nerve cell bodies: (1) the substantia nigra, pars compacta (SNc), (2) the ventral tegmental area (VTA), (3) the retrorubral area (RRA), and (4) the periaqueductal gray (PAG). The SNc composed the vast majority of DA-immunostained neurons. Most of these neurons were relatively large (mean diameters: 35 x 15 micron) and varied in shape from fusiform to polygonal, but a few smaller (16 x 10.5 micron) globular cells were dispersed among them. The caudal two-thirds of the SNc was particularly rich in DA somata. Rostrally, these DA cells formed several distinct columns impinging deeply upon the underlying pars reticulata. Large oval sectors mostly devoid of immunoreactivity were delineated by these trabeculae. The long dendritic processes of DA neurons in the SNc were generally oriented in prominent dorsoventral bundles the ventralmost portion of which arborized diffusely along the dorsal surface of the cerebral peduncle. In the VTA, the DA neurons were regrouped in a triangular zone located dorsal to the interpeduncular nucleus, medial to the substantia nigra and ventral to the oculomotor nucleus. These DA cells were of medium size (19 x 10.5 micron), globular or fusiform, and usually showed one or two thick primary dendrites oriented dorsoventrally. The DA cells in the RRA lay in continuity with the most caudal DA-containing elements of the substantia nigra but could be distinguished by their smaller size (26 x 12 micron), shorter and more profusely branched dendrites, and darker immunostaining. These DA neurons were characteristically scattered among and medial to the fibers of the medial lemniscus, and a few could be observed as far caudally as the pedunculopontine nucleus. In the PAG, DA-immunostained neurons were seen in the rostral half of the mesencephalic central gray and predominated in its ventral half. These cells were of medium size (22.5 x 10 micron) and some of them were found in proximity to the ventricular lining. At caudal levels, the DA-positive cells in the PAG did not intermingle with dorsal raphe neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Serotonin innervation in adult rat neostriatum. I. Quantified regional distribution.

The distributional features of the serotonin (5-HT) innervation in adult rat neostriatum were examined and quantified using two complementary chemoanatomical methods: 5-HT-immunohistochemistry on serial histological sections and radioautography after [3H]5-HT uptake in whole cerebral hemisphere slices. As visualized and measured after peroxidase-antiperoxidase immunostaining, the neostriatal 5-HT fiber network pervading the entire neostriatum was 2-3 times denser in its ventral than dorsal parts, and showed a slight rostrocaudal increase in density. Its axonal length ranged from 1.06 to 4.18 m per mm3 of striatal tissue. Radioautographic counts of the [3H]5-HT-labeled axon varicosities within comparable sectors of the neostriatum showed good correlation with this distribution pattern. As extrapolated after appropriate corrections for incomplete detection at the chosen exposure time and from the thickness of sections examined, the number of neostriatal 5-HT varicosities (innervation density) ranged from 1.5 to 4.8 millions and averaged 2.6 millions per mm3 of tissue. These quantitative results provided new insights into the topographical organization of the dorsal raphe-neostriatal 5-HT projection system. They already allow for meaningful correlations with currently available microchemical data on intrastriatal 5-HT levels and should also be of considerable significance when as precise information becomes available on the number and localization of different 5-HT receptors and uptake carriers within rat neostriatum.

Animals↗

Distribution of GABA-immunoreactive neurons in the basal ganglia of the squirrel monkey (Saimiri sciureus).

The distribution of GABA-immunoreactive neurons was visualized in the basal ganglia of the squirrel monkey (Saimiri sciureus), by using a highly specific antiserum raised against GABA-glutaraldehyde-lysyl-protein conjugate and revealed by the indirect peroxidase-antiperoxidase immunohistochemical method. In the dorsal striatum, GABA-immunoreactive nerve cell bodies were small to medium in size (sectional area ranging from 90 to 125 microns2), but some larger ones (500-600 microns2) were also found. These cells displayed no obvious clustering but were significantly more numerous in the caudate nucleus than in the putamen; their number was also markedly greater at caudal than at rostral striatal levels. A moderate number of evenly distributed positive axon terminals were visible in both the caudate nucleus and the putamen. In the ventral striatum, GABA-immunoreactive nerve cell bodies and axon terminals were seen in fair number within the nucleus accumbens and in the deep layers of the olfactory tubercle. Many positive terminals but no somata were found in the islands of Calleja. In the globus pallidus, virtually all nerve cell bodies were GABA-immunoreactive and the neuropil exhibited a multitude of positive terminals. In the substantia innominata, clusters of small, globular GABA-immunoreactive somata were scattered among aggregates of larger, nonimmunoreactive neurons belonging to the nucleus basalis, and the whole region showed a low to moderate number of evenly spread GABA-positive terminals. In the subthalamic nucleus, nerve cell bodies were generally surrounded by several GABA-positive terminals but were not themselves immunoreactive. The substantia nigra showed many GABA-immunoreactive somata, which predominated in the pars lateralis and diminished progressively in number along the lateromedial axis of the pars reticulata. These cells formed a rather pleomorphic group comprising round, fusiform, or polygonal elements of relatively large size (sectional area ranging from 200 to 800 microns2). In the pars compacta and ventral tegmental area, a few GABA-immunoreactive neurons of small size were dispersed among larger, unreactive neurons. In both pars lateralis and pars reticulata of the substantia nigra, the number of GABA-positive terminals was high and their distribution was rather uniform; a smaller number were visible in the pars compacta of the substantia nigra and in the ventral tegmental area. The present results demonstrate that GABA-containing neurons are widely and heterogeneously distributed in the various components of the squirrel monkey's basal ganglia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Innervation and reinnervation of rat inferior olive by neurons containing serotonin and substance P: an immunohistochemical study after 5,6-dihydroxytryptamine lesioning.

Serotonin (5-HT) and substance P (SP) immunoreactive axon terminals were visualized in the inferior olivary complex (IOC) of adult rats, 1 to 2 weeks or 6 to 12 months after cerebro-ventricular injection of 5,6-dihydroxytryptamine (5,6-DHT). In normal or saline-injected controls of the same age, there was some overlap between the respective distributions of 5-HT- and SP-immunostained axonal varicosities among the various subdivisions of IOC. At short time intervals after the 5-HT axotomy, almost as many degenerating axonal profiles showed immunoreactivity to SP as to 5-HT throughout the IOC, suggesting the coexistence of both transmitters within the same fibres. A few areas continued to exhibit characteristic patches of 'normal-looking' SP immunoreactivity, consistent with a distinct innervation by SP fibres without coexistent 5-HT. At prolonged survival times after 5,6-DHT treatment, there was a massive increase in the number-and striking similarity in the distribution-of IOC axonal varicosities immunostained for SP as well as for 5-HT. This neo-innervation involved certain subdivisions of the IOC normally receiving fibres of either type (e.g. dorsal accessory olive), but also others normally poor in 5-HT and/or SP (e.g. medial accessory olive). It remains to be determined if this abundance of 5-HT-SP terminals in the 'hyperinnervated' IOC reflected a particular capacity to express both transmitters in regenerating 5-HT neurons.

5,6-Dihydroxytryptamine↗

Regional and laminar density of the dopamine innervation in adult rat cerebral cortex.

The topographic distribution and density of the dopamine innervation in adult rat cerebral cortex were investigated by means of a recently improved radioautographic procedure for the light microscopic visualization and counting of monoamine axonal varicosities. Dopamine terminals were specifically labeled by high-affinity uptake in whole cerebral hemisphere slices incubated for 15 min at 35 degrees C with 10(-6) M tritiated dopamine in the presence of 10(-4) M pargyline and 5 X 10(-6) M desipramine. The slices were subsequently fixed, embedded in Epon and processed for light microscope radioautography as large 4-micron-thick (whole hemisphere) or smaller, semi-thin sections (selected areas). In radioautographs of serial semi-thin sections exposed for various periods of time, the number of labeled axonal varicosities reached a plateau after 12-14 days of exposure. Counts on such sections of increasing thickness allowed to calculate a correcting factor to transform numbers obtained from 4-micron-thick sections into their equivalent for a tissue thickness of 0.5 micron from which all varicosities were detected. The number of labeled varicosities could then be expressed per mm3 of tissue after measuring their mean caliper diameter in electron microscope radioautographs. As visualized at 3 transverse levels representing most of the major cytoarchitectonic divisions of cerebral cortex, two novel aspects were recognized in the topographic distribution of dopamine terminal: (1) the presence of a dopamine innervation in layer VIb of the frontal, parietal, temporal and occipital neocortex, and (2) a significant contingent of dopamine varicosities within the deep and not only upper layers of supragenual cingulate cortex. A fair number of dopamine varicosities were also detected in the upper layers of the dorsomedial frontal area, in the retrosplenial and adjacent occipital cortex as well as in the ventral subiculum and field CAl of the hippocampus. As measured in 10 sectors representing different cortical regions, the highest density of dopamine innervation was found in the supragenual cingulate cortex (1.7 X 10(6] and particularly in its layers II and III (3.1 X 10(6)). A slightly lower density was measured in the anteromedian "prefrontal" cortex (1.0 X 10(6)). The rostrorhinal and the perirhinal cortex showed moderate dopamine innervation (3.0 and 5.5 X 10(5)) with varicosities in every layer. The piriform and the posterior entorhinal cortex were also moderately and ubiquitously innervated (2.5 and 3.0 X 10(5)).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Dopaminergic projection from nucleus raphe dorsalis to neostriatum in the rat.

The existence of a dopamine (DA) projection from nucleus raphe dorsalis (RD) to neostriatum was demonstrated in the rat by combined tyrosine hydroxylase (TH) immunohistochemistry and radioautography after retrograde axonal transport of [3H]noradrenaline ([3H]NA). Intrastriatal injections of [3H]NA were carried out in normal rats or after ipsilateral destruction of the nigrostriatal DA system by injection of 6-hydroxydopamine (6-OHDA) into the substantia nigra. Some 1,000 TH-positive nerve cell bodies were counted within the confines of RD as defined by its content in serotonin (5-HT) neurons. These DA neurons occupied the upper third of the RD and they were part of its small cell population. In all cases, a small proportion of the TH-immunoreactive nerve cell bodies in RD were retrogradely radiolabeled. Radiolabeled but immunonegative cells were exceedingly rare. The double-labeled neurons were generally more numerous after elimination of the nigrostriatal DA innervation than in normal rats. They mostly lay within the ventral portion of the medial subdivision of RD and always predominated on the [3H]NA- injected side. Some were also present in nucleus linearis caudalis. It was concluded that [3H]NA had been taken up and retrogradely transported exclusively by catecholamine neurons; part of the DA cell group in RD projects to the neostriatum; and that most if not all non-5-HT neurons projecting from RD to neostriatum are likely to be dopaminergic.

Animals↗