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Evidence for volume transmission in the dopamine denervated neostriatum of the rat after a unilateral nigral 6-OHDA microinjection. Studies with systemic D-amphetamine treatment.

In the present study the hypothesis has been tested if the dopamine releasing drug D-amphetamine via volume transmission can, at least partly, restore dopamine communication in the dopaminergically denervated neostriatum of rats. The experimental model used, has been a unilateral 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine neurons, based on nigral microinjections of this neurotoxin. Studies on c-fos like immunoreactivity after systemic D-amphetamine treatment demonstrated a wide-spread appearance of c-fos like immunoreactive neuronal nuclear profiles within the neostriatum on both the unlesioned and denervated side. In the unlesioned neostriatum a peak density of c-fos like immunoreactive profiles was found within the central part of the neostriatum, while on the denervated side the distribution pattern of c-fos like immunoreactive profiles peaked medially and gradually declined in a lateral direction. The microdialysis experiments demonstrated, after systemic d-amphetamine treatment, a marked and sustained increase of extracellular dopamine levels in the neostriatum on the unlesioned side, while no increases in the extracellular dopamine levels were observed on the dopaminergically denervated neostriatum. In the electrophysiological experiments, systemic D-amphetamine treatment produced an inhibition of the neuronal activity on the denervated side which showed a significant increase in basal discharge rate compared with the recordings obtained from the striata on the unlesioned side. The present immunocytochemical microdialysis and electrophysiological analysis provides evidence that in the unilaterally markedly dopamine depleted neostriatum with clearcut signs of dopamine receptor supersensitivity (rotational behaviour results), dopamine transmission may be partly restored via systemic D-amphetamine treatment through the release of dopamine, predominantly from the unlesioned neostriatum, which may diffuse into the cerebrospinal fluid to reach the contralateral dopaminergically denervated neostriatum.

Animals

Cell types of the auditory caudomedial neostriatum of the starling (Sturnus vulgaris).

Cell types of the auditory neostriatum in the starling forebrain are described. This area in the caudal neostriatum is defined neurophysiologically by the appearance of auditory neurons. Through use of the rapid Golgi technique, four types of neurons are identified, mainly on the basis of their processes: Neurons with long descending axons and thick dendrites rich in spines (type 1), neurons with long ascending axons and thin dendrites poor in spines (type 2), short-axon neurons (type 3), and microneurons (type 4). The axons of the long neurons pass outside the confines of the auditory neostriatum. Among neurons of type 1; some of the long descending axons directed toward the lower brain centers enter the capsula interna occipitalis (CIO). The descending axons give off many collaterals within the auditory neostriatum. With neurons of type 2; most of the ascending axons cross the lamina hyperstriatica, enter the hyperstriatum ventrale, and arborize near its periventricular region. Some of the long ascending axons reach the overlying hyperstriatum ventrale, pars caudale (HVc, the vocal control area). Among neurons of types 3 and 4; the axons of short-axon neurons and of microneurons end with fine branches within the auditory neostriatum. The dendrites of long-axon neurons are oriented in specific directions, whereas those of short-axon neurons and of microneurons do not show a definite pattern of orientation. In the region of the auditory neostriatum that lies immediately adjacent to the midline of the brain, the first three types of neurons are arranged around the central core known as field L, which is composed of the microneurons and the terminal ramifications of auditory afferents. Laterally the microneurons, along with the fibers of the input tract, undergo a rostral shift to occupy a more peripheral position within the auditory neostriatum. The neurons of the auditory neostriatum are compared with those of the mammalian auditory cortex, and a functional classification of nerve cells into projection neurons, association neurons, and interneurons is proposed.

Animals

Amino acid levels and gamma-aminobutyric acidA receptors in rat neostriatum, cortex, and thalamus after neonatal 6-hydroxydopamine lesion.

The amino acid gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in brain, and GABAergic neurons have been proposed to play a major role in basal ganglia physiology. In the neostriatum (caudate putamen), medium-sized aspiny interneurons, as well as neostriatal output neurons that project to several brain regions, use GABA as their neurotransmitter. Dopamine fibers arising from the substantia nigra represent a major input to the neostriatum where, besides their classic neurotransmitter role, they are seemingly involved in the regulation of amino acid neurotransmitter release. To further characterize the nature of some of the amino acid/dopamine interactions, selective dopaminergic deafferentations were produced in neonatal rats (3 days postnatal) by intraventricular administration of the neurotoxin 6-hydroxydopamine (6-OHDA); the noradrenergic neurons were protected by prior administration of desmethylimipramine. After a 3-month survival, levels of catecholamines, indoleamines, and amino acids were determined in cingulate cortex, thalamus, and neostriatum. In addition, GABAA receptors were measured in membrane preparations from these three regions, using the specific agonist [3H]muscimol. In the 6-hydroxydopamine-lesioned rats, levels of dopamine and its metabolites homovanillic acid, 3,4-dihydroxyphenylacetic acid, and 3-methoxytyramine were decreased, as expected, in cortex and neostriatum, but remained unmodified in thalamus. In all three regions, serotonin content was increased; its metabolite, 5-hydroxyindole-3-acetic acid, was also elevated, but only in cortex and neostriatum. The levels of GABA were increased in neostriatum and thalamus, but remained unmodified in cortex. Glycine was increased in all three regions examined. There were also increases of phosphatidylethanolamine and serine in thalamus, and of aspartic acid and alanine in neostriatum. The density of GABAA binding sites was increased in neostriatum, but remained unchanged in cortex and thalamus. The changes in amino acid levels and [3H]muscimol binding sites induced by a neonatal 6-hydroxydopamine treatment differ from those found after similar lesions in adult animals, possibly because of the plastic and synaptic rearrangements that can still occur during early postnatal development. The present results also demonstrate that adaptations occur in response to a dopaminergic deafferentation at an early age and that these exhibit a regional specificity.

Amino Acids

Modulation of neurotransmitter release by cholecystokinin in the neostriatum and substantia nigra of the rat: regional and receptor specificity.

The effect of cholecystokinin peptides on the release of dynorphin B, aspartate, glutamate, dopamine and GABA in the neostriatum and substantia nigra of the rat was investigated using in vivo microdialysis. Sulphated cholecystokinin-8S in the dialysis perfusate (1-100 microM) induced a concentration-dependent increase in extracellular dynorphin B and aspartate levels, both in the neostriatum and substantia nigra. Striatal dopamine levels were only increased by 100 microM of cholecystokinin-8S, while in the substantia nigra they were increased by 10-100 microM of cholecystokinin-8S. Extracellular GABA and glutamate levels were increased following 100 microM of cholecystokinin-8S only. Striatal cholecystokinin-8S administration also produced a significant increase in nigral dynorphin B levels. Local cholecystokinin-4 (100 microM) produced a moderate, but significant, increase of extracellular dynorphin B and aspartate levels in the neostriatum and substantia nigra. No effect was observed on the other neurotransmitters investigated. A 6-hydroxydopamine lesion of the nigrostriatal dopamine pathway did not affect the increases in dynorphin B and aspartate levels produced by local administration of cholecystokinin-8S. Basal extracellular GABA levels were increased significantly in both the neostriatum and substantia nigra ipsilateral to the lesion. Nigral glutamate and aspartate levels were also increased in the lesioned substantia nigra, but in the lesioned neostriatum aspartate levels were decreased. The cholecystokinin-B antagonist L-365,260 (20 mg/kg, s.c.), but not the cholecystokinin-A antagonist L-364,718 (devazepide; 20 mg/kg, s.c.), significantly inhibited the effect of cholecystokinin-8S on striatal dynorphin B and aspartate levels. In the substantia nigra, however, the effect of cholecystokinin-8S on dynorphin B and aspartate levels was inhibited to a similar extent by both L-365,260 and L-364,718. Pretreatment with L-364,718, but not with L-365.260, prevented the increase in nigral dopamine levels produced by nigral cholecystokinin-8S administration. Taken together, these results suggest that cholecystokinin-8S modulates dynorphin B and aspartate release in the neostriatum and substantia nigra of the rat via different receptor mechanisms. In the neostriatum, the effect of cholecystokinin-8S on dynorphin B and aspartate release is mediated via the cholecystokinin-B receptor subtype, while in the substantia nigra, cholecystokinin-8S modulates dynorphin B and aspartate release via both cholecystokinin-A and cholecystokinin-B receptor subtypes. Cholecystokinin-8S modulates dopamine release mainly in the substantia nigra, via the cholecystokinin-A receptor subtype.

3,4-Dihydroxyphenylacetic Acid

The rodent neostriatum: a Golgi analysis.

In the adult rodent, coronal sections of Golgi impregnations of the neostriatum display a compact segregation of axon fascicles, neuronal clusters, and dendritic bundles thus forming an areolar configuration. Isolated neurons are rarely seen. The dorsomedial region of the neostriatum appears free of axon fascicles and dendritic bundles. Horizontal and sagittal sections of the neostriatum show clusters of cells parallel to axon fascicles. The neurons exhibit spine-laden dendrites with an initial spine-free segment. Neonatal impregnations exhibit a different configuration. Neonatally, cells tend to cluster but there is no bundling of dendrites. Neurons are spine-free or have protospines on the soma and the dendrites, including the initial segment. Transition from neonate to adult configuration is discernible at about 15 days after birth. The neostriatum of carnivores exhibits a different structure from the rodent neostriatum. This difference is associated with a developed anterior limb of the internal capsule in the carnivore. The axon fascicle-free portion of the carnivore neostriatum lacks dendritic bundles and pallisades. Portions near the capsule with axon fascicles appear similar to the rodent neostriatum with dendritic bundlings and pallisading. Such findings emphasize the importance of total neuronal configuration (neuronal-architectonics) in morphologic analyses.

Animals

The organization of the nucleus basalis-neostriatum complex of the mallard (Anas platyrhynchos L.) and its connections with the archistriatum and the paleostriatum complex.

The pattern of connections between the nucleus basalis, neostriatum, hyperstriatum ventrale, paleostriatum complex and archistriatum in the mallard has been analysed using Nissl material and a combination of neuroanatomical tracing procedures (autoradiography, horseradish peroxidase and horseradish peroxidase-wheat germ agglutinin histochemistry, lesion/degeneration technique). The frontal part of the mallard's telencephalon is characterized by its multilayered organization and the predominantly vertical arrangement of the connecting fiber systems. The nucleus basalis, endstation of the ascending sensory trigeminal system, is a large laminar cell area with a dorsal and a ventral layer. The overlying neostriatum frontale can be subdivided into a medial, a dorsal and a ventral intermediate, and a lateral area. The nucleus basalis has distinct connections with the ventral layer and sparse connections with the dorsal layer of the intermediate neostriatum, and abundant reciprocal connections with the ventral layer of the hyperstriatum ventrale. The ventral intermediate neostriatum also has reciprocal connections with the hyperstriatum ventrale; its projections overlap partly with those from the nucleus basalis. The ventral layer of the intermediate neostriatum frontale has a distinct projection upon the paleostriatum augmentatum. The dorsal layer sends fibers to the lateral neostriatum, to the rostral "sensorimotor" part of the archistriatum and to the lateral zone of the lobus parolfactorius. Another source of archistriatal afferents is the paleostriatum ventrale, an area that may also send fibers to the brainstem. Figure 21 summarizes the connections described in this paper. The functional significance of this organization is discussed in relation to its possible role in the guidance of pecking and other feeding behaviors in the mallard. Differences in the organization of the systems in pigeon and mallard are related to the differing degrees of visual and tactile (trigeminal) contributions to feeding in the two birds. It is suggested that the pattern of reciprocal connections between the hyperstriatum ventrale and the nucleus basalis and ventral intermediate neostriatum frontale forms the neuroanatomical substrate for a "comparator-system".

Animals

Changes of D1 and D2 receptors in adult rat neostriatum after neonatal dopamine denervation: quantitative data from ligand binding, in situ hybridization and iontophoresis.

The specific binding of [3H]SCH23390 to D1 and of [3H]raclopride to D2 dopamine receptors was measured by autoradiography in the rostral and caudal halves of neostriatum and in the substantia nigra of adult rats subjected to near total destruction of nigrostriatal dopamine neurons by intraventricular 6-hydroxydopamine soon after birth. Three months after this lesion, [3H]SCH23390 binding (D1 receptors) was slightly but significantly decreased in the rostral neostriatum (22%), but unchanged in its caudal half and in the substantia nigra. In contrast, [3H]raclopride binding (D2 receptors) was considerably increased throughout the neostriatum (10-40%), while markedly decreased in the substantia nigra (80%). In the rostral neostriatum, there were no parallel changes in D2 receptor messenger RNA levels, as measured by in situ hybridization on adjacent sections. Caudally, however, slight but significant increases in D2 messenger RNA could be observed (10-20%). As assessed by quantitative iontophoresis, there was a marked enhancement (63%) of the inhibitory responsiveness of spontaneously firing units in the rostral neostriatum to dopamine and the D1 agonist, SKF38393, in neonatally lesioned compared to control rats. On the other hand, responsiveness to PPHT, a potent D2 agonist, appeared to be unchanged. Such opposite changes in the number of D1 and D2 binding sites, dissociated from the expression of D2 receptor messenger RNA and from the sensitivity to dopamine and D1 and D2 agonists, suggested independent adaptations of these various parameters following the neonatal dopamine denervation of neostriatum. They also provided further evidence for mechanisms other than the dopamine innervation in the control of the expression of neostriatal D2 receptor messenger RNA during ontogenesis, and emphasized that the effects of dopamine and its D1 and D2 agonists in neostriatum do not depend strictly on the number of D1 and D2 primary ligand recognition sites.

Animals

Comparison of transmitter amino acid levels in rat globus pallidus and neostriatum during hypoglycemia or after treatment with methionine sulfoximine or gamma-vinyl gamma-aminobutyric acid.

The levels of amino acids in globus pallidus, a structure heavily innervated with gamma-aminobutyric acid (GABA)-ergic terminals but few glutamergic terminals, were compared with the levels in neostriatum, a structure richly innervated with glutamergic terminals but intermediate in GABAergic terminals. The level of glutamate in neostriatum was twice as high as in globus pallidus whereas the level of GABA in globus pallidus was three times higher than in neostriatum. The level of aspartate was similar in both regions whereas the level of glutamine was correlated with the level of glutamate. Methionine sulfoximine, a glutamine synthetase inhibitor, reduced the level of glutamine to 10-20% of control in both structures. This reduction was accompanied by the largest decrease in the level of glutamate in neostriatum, indicating that transmitter glutamate turns over more rapidly than other glutamate pools. Likewise, insulin decreased the levels of glutamate and glutamine more in neostriatum than in globus pallidus. gamma-Vinyl GABA increased the level of GABA in globus pallidus more than in neostriatum although the percent increase was largest in neostriatum. Treatment with gamma-vinyl GABA was accompanied by a large reduction in the level of GABA, indicating that a substantial proportion of the glutamine pool is linked to GABA metabolism.

Amino Acids

Prenatal formation of cortical input and development of cytoarchitectonic compartments in the neostriatum of the rhesus monkey.

The timing, hemispheric laterality, and mode of termination of input from the prefrontal association cortex to the neostriatum were studied in fetal and neonatal rhesus monkeys using autoradiography for tracing connections. In addition, the cytological maturation of the neostriatum was examined in Nissl-stained sections from the same and other monkeys of selected prenatal and postnatal ages. A small contingent of corticostriatal axons reaches both the caudate nucleus and the putamen by the 69th embryonic day (E69) of the 165-day gestation period in this species and steadily expands over the next 3 fetal months. Throughout this period, ipsilateral perfrontostriatal connections predominate, and only a small and variable amount of label is detectable over the contralateral neostriatum. A major feature of the developing corticostriatal projection is a transfiguration in the distribution of its terminals: from E69 to E95, cortical terminals are distributed uniformly among neostriatal neurons; beginning around E105, areas of higher and lower grain density begin to emerge until finally, by E133, 250- to 500-micrometers-wide circular and elliptically shaped label-free cores perforate a field of densely labeled cortical terminals as in the neostriatum of the adult monkey (Goldman, P. S., and W. J. H. Nauta (1977) J. Comp. Neurol. 171: 369-386). The cytoarchitectonic composition of the neostriatum also changes during gestation: from E69 through E95, the small postmitotic neurons of the immature neostriatum are packed densely and, for the most part, are distributed homogeneously; by E105, they become segregated into cellular islands consisting of densely packed neurons that are encapsulated by fiber-rich annuli and embedded in a matrix of less densely arrayed neurons. The shape and size of the islands in Nissl-stained sections correspond to label-free cores in autoradiograms of fetuses with cortical injections, while the surrounding annuli and adjacent matrix cells correspond to areas of dense accumulation of label. Thus, the formation of the corticostriatal projection in primates involves a transformation in the distribution of ingrowing terminals synchronized with changes in cellular organization of the neostriatum.

Adrenal Cortex Hormones

Developmental expression of KG-CAM in the rat neostriatum.

The present study examines the developmentally regulated expression pattern of an Ig superfamily member, KG-CAM, in the neostriatum of the rat. KG-CAM is a 90-kDa glycoprotein that is related to the DM-GRASP/Neurolin family of adhesion molecules. In the embryonic and early postnatal neostriatum, the distribution of KG-CAM correlates with the distribution of dopaminergic terminals. Early in neostriatal development, KG-CAM is found in the tyrosine hydroxylase-positive patches. In the maturing neostriatum, the levels of KG-CAM remain high within the patches, and KG-CAM upregulates in the matrix compartment. As the neostriatum is reaching its adult morphology, 5 weeks postnatal, the expression of KG-CAM in the matrix is approximately equal to that of the patches. When the distribution of KG-CAM is examined at the ultrastructural level, the immunoreactivity is localized to the external surface of neuronal and glial profiles in the neuropil. KG-CAM does not appear to be associated with the guidance of dopaminergic axons from the substantia nigra to the striatum, for this pathway is not immunopositive for this member of the Ig superfamily. The present study identifies an Ig superfamily member, KG-CAM, that appears to play a major role in the development of the neostriatum. Furthermore, the high levels of KG-CAM in the adult neostriatum suggest that this Ig superfamily member may be involved in maintaining the integrity of this structure in the adult rat.

Activated-Leukocyte Cell Adhesion Molecule

Synaptic connections of enkephalin-immunoreactive nerve terminals in the neostriatum: a correlated light and electron microscopic study.

Two different antisera to leucine-enkephalin were used to study the localization of enkephalin-like immunoreactive material in the neostriatum and globus pallidus of the rat, by means of the unlabelled antibody-enzyme method. Thin immunoreactive varicose fibres are scattered throughout the neostriatum. In the ventral striatum, fibres come together and follow a relatively straight course for several micrometers, forming tube-like structures which can be traced to cell bodies; these cell bodies are completely surrounded by immunoreactive fibers. Occasional immunoreactive varicose fibres are also found close to another type of neuron throughout the whole neostriatum. Examination by electron microscopy of immunoreactive structures that had been identified first in the light microscope, showed that each of the nearly 200 varicosities examined was a vesicle-containing bouton that formed a synaptic contact. Rarely were asymmetrical synaptic contacts found between immunoreactive boutons and dendritic spines. All other synapses formed by enkephalin-immunoreactive boutons were symmetrical. Two types of postsynaptic neuron were identified; the first type was a medium-sized neuron with the ultrastructural features of a typical striatal spiny neuron. The second type had a larger perikaryon surrounded by numerous immunoreactive varicosities that were found to be boutons forming symmetrical synapses. The long dendrites of this second type of neuron likewise received a dense input of immunoreactive boutons forming symmetrical synapses; such ensheathed dendrites were found to be the tube-like structures seen in the light microscope. The ultrastructural features of these neurons, notably a highly indented nucleus, were those of a rare type of striatonigral neuron. In the globus pallidus, all the enkephalin-immunoreactive boutons studied formed symmetrical synapses with ensheathed dendrites and perikarya that were similar to the latter type of postsynaptic neuron in the neostriatum. Axo-axonic synapses involving immunoreactive boutons were not seen in our material. The results are consistent with the view that enkephalin-like substances may be synaptic transmitters in the neostriatum and that they may have different actions according to the nature of the postsynaptic target. The finding that one type of neostriatal neuron, and a very similar neuron in the globus pallidus, receives multiple enkephalin-immunoreactive boutons all over its perikaryon and along its dendrites indicates a potentially important role of enkephalin in the convergence of information within the neostriatum and pallidum on to output neurons.

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

An electron microscopic morphometric comparison of tyrosine hydroxylase immunoreactive innervation in the neostriatum and the nucleus accumbens core and shell.

The synaptic targets and size distributions of the sectioned profiles of tyrosine hydroxylase immunoreactive fibers and boutons in the neostriatum and shell and core of the nucleus accumbens were evaluated. Significantly more synaptic contacts where dendrite shafts are the postsynaptic element were observed in the shell than in the core of the nucleus accumbens or neostriatum. Relative to the core and neostriatum, a significantly greater proportion of the tyrosine hydroxylase immunoreactive innervation of the accumbal shell consisted of thin fiber and small bouton profiles. Thus, with regard to the morphometric parameters evaluated, the core of the nucleus accumbens is aligned with neostriatum and the shell is different from the core and neostriatum. In the light of these data, it is probably that the effects of the dopaminergic innervation in the core resemble the effects in neostriatum more than do those in the shell.

Animals

Dopamine-regulated phosphorylation of synaptic vesicle-associated proteins in rat neostriatum and substantia nigra.

Dopamine, acting through dopamine D1 receptors and cyclic AMP-dependent protein kinase, has been found to increase the state of phosphorylation of the synaptic vesicle-associated phosphoproteins synapsin I and protein III in slices of rat neostriatum and substantia nigra. In the neostriatum, the effect of dopamine was mimicked by SKF 38393, a D2 receptor agonist, and was abolished by preincubation of the slices with fluphenazine or SCH 23390, antipsychotic drugs which are potent D1 receptor antagonists, but not by the D2 receptor antagonists l-sulpiride or spiroperidol. The maximal effect of dopamine in the neostriatum represented approximately 30-35% of the maximal effect induced by 8-bromo cyclic AMP, suggesting that a similar fraction of nerve terminals in the neostriatum may express the dopamine D1 receptor. Evidence for a small population of beta-adrenergic receptors regulating nerve terminal protein phosphorylation in the neostriatum, distinct from the D1 dopamine receptors, was also obtained. In the substantia nigra, the effect of dopamine also appeared to be mediated through a D1 dopamine receptor, since it was abolished by fluphenazine and SCH 23390. The maximal effect of dopamine in the substantia nigra represented approximately two-thirds of the effect induced by 8-bromo cyclic AMP, suggesting that a similar fraction of nerve terminals in the substantia nigra may express the dopamine D1 receptor. The ability of dopamine D1 receptor activation to stimulate both synapsin I and protein III phosphorylation and GABA release in both the neostriatum and substantia nigra may be causally linked.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

A comparative quantitative and morphological study of ageing in the mouse neostriatum, indusium griseum and anterior commissure.

The glia:neuron ratio increased between 5 and 9 months in the neostriatum and indusium griseum and thereafter remained constant until 18 months-of-age. Between 18 and 22 months the glia:neuron ratio did not change in the neostriatum, but increased significantly in the indusium griseum due to a combination of a loss of neurons and an increase in glia. The 6--9 months rise was mainly due to an increase in the number of astrocytes in both regions although there was some increase in oligodendrocytes at this time. The increase in glia in the indusium griseum between 18 and 22 months was due to an increase in both astrocytes and microglia. In the anterior commissure, the pattern of glial change was almost identical in both limbs with oligodendrocytes increasing between 6 and 9 months then decreasing between 9 and 18 months. Astrocytes decreased between 6 and 18 months. Between 18 and 22 months oligodendrocytes and microglia both increased in number. There was a decrease in glioblasts in both limbs with age. The age at which lipofuscin appeared was different in each type of glial cell and in each region studied. Microglia contained lipofuscin at 6 months in all regions. Astrocytes first contained lipofuscin at 6 months in the neostriatum, at 9 months in the indusium griseum and at 15 months in the anterior commissure. Oligodendrocytes first contained lipofuscin at 12 months in the anterior commissure, at 18 months in the indusium griseum and at 18 months in the neostriatum. Ependymal cells adjacent to the neostriatum contained lipofuscin and osmiophilic lipid at 6 months but by 12 months the latter had become much less osmiophilic. Foamy pericytes were found in all regions: from 6 months in the neostriatum; from 9 months in the indusium griseum and from 15 months in the anterior commissure. These contained lipid droplets, were only found adjacent to arterioles or venules, and were likely Ibrahim's neurolipomastocytes. The response of glia to ageing varies in different regions of grey matter, but is similar in two different regions of white matter. These age changes may be related to different levels of metabolic activity of glia in different parts of the brain.

Aging

The effect of microinjections of morphine and haloperidol into the neostriatum and the nucleus accumbens on self-stimulation behaviour.

The effect of stereotaxic injections of morphine and haloperidol via permanently implanted cannulas into the neostriatum, the nucleus accumbens or the ventricular system was studied on self-stimulation behaviour of rats with electrodes implanted into the ventral tegmentum. The self-stimulation rate was depressed by injections of haloperidol into the neostriatum or into the nucleus accumbens. Unilateral injections of haloperidol into the neostriatum depressed the self-stimulation rate either with applications ipsilateral to the electrode or contralateral to the electrode. Bilateral applications of haloperidol into the neostriatum (2 X 2.5 mug) were more effective as unilateral applications (5 mug) and were more effective as applications into the ventricular system (5 mug). Morphine had a strong depressant action on self-stimulation when applied into the ventricular system and was ineffective when applied into the neostriatum. It is concluded that these results do not favour the hypothesis that morphine interferes with dopaminergic transmission with the neostriatum.

Animals

The 'marginal division': a new subdivision in the neostriatum of the rat.

Using a combination of anterograde and retrograde (Phaseolus vulgaris leucoagglutinin; PHA-L and wheat germ agglutinin conjugated horseradish peroxidase; WGA-HRP) tract-tracing methods and histochemical techniques, a new subdivision of the neostriatum, the marginal division, has been found in the rat brain. The marginal division is approximately 120 microns wide and is located at the caudal extent of the neostriatum and surrounds the rostral edge of the globus pallidus. The neuronal somata of the marginal division are mostly fusiform in shape, with their long axes running parallel to the border between the striatum and the globus pallidus. Histochemically, the marginal division is lighter in AChE staining, is more densely filled with Met-enkephalin-immunoreactive terminals, and has fewer choline acetyltransferase (ChAT)-immunoreactive neurons than does the rest of the neostriatum. Injections of PHA-L or WGA-HRP demonstrated that the projections of the marginal division differ from those of the main body of the striatum. The striatopallidal projection from the marginal division terminates in the caudal-most part of the globus pallidus which is rich in cholinergic neurons. In contrast, the projection from the main region of the neostriatum terminates in two bands in the globus pallidus, both of which are rostral to the area of termination of the fibres from the marginal division. The striatonigral fibres from the marginal division terminate in the caudal part of the substantia nigra pars reticulata whereas the rest of neostriatum projects to a more rostral region. Based on its cellular morphology, immunohistochemistry and projection pattern, we conclude that the marginal division of the striatum is a distinct subdivision of the neostriatum.

Acetylcholinesterase

Quantification of the serotonin hyperinnervation in adult rat neostriatum after neonatal 6-hydroxydopamine lesion of nigral dopamine neurons.

Light microscope autoradiography after uptake and storage of tritiated serotonin (5-HT) in brain slices was used to count 5-HT axon terminals (varicosities) in the 5-HT-hyperinnervated neostriatum of adult rats subjected to neonatal 6-hydroxydopamine treatment and age-matched, normal controls. After correction for incomplete autoradiographic exposure and for section thickness, the results were expressed in millions of varicosities per mm3 of tissue. Control values ranged from 4.8 in the rostral to 6.3 in the caudal neostriatum (5.8 at intermediate level), for an average of 5.6. The corresponding values in 5-HT-hyperinnervated tissue ranged from 9.7 to 7.7 (8.8 at intermediate level), for an average of 8.7 and increases of 102%, 52% and 22% above control in the rostral, intermediate and caudal neostriatum, respectively (average increase of 55%). These data confirmed the predilection of the 5-HT hyperinnervation for the rostral neostriatum and demonstrated its presence in the caudal neostriatum also.

Animals