Valerie B. Domesick

The fasciculus cinguli in the rat

Abstract The white matter of the medial cortex in the rat was examined along its longitudinal extent from the genu to the splenium of the corpus callosum. The problem of distinguishing thalamic from cortical contributions to this fiber complex was approached experimentally by tracing axon degeneration elicited by lesions in the anterior thalamus and the cingulate cortex6, respectively. The results indicate that the fasciculus cinguli is primarily a thalamocortical fiber stratum, contiguous with that of the remaining cortex, and forming with the latter the external medullary stratum of the cortical white matter. In their course to the medial cortex, thalamocingulate fibers pass rostralward from the thalamus. At levels extending from the anterior commissure forward beyond the genu of the corpus callosum, the fibers first turn dorsalward, penetrating the callosal fiber sheet, and then medialward to become enclosed in the fasciculus cinguli. The appearance of these fibers is most striking at levels anterior to the genu where they take an almost vertical sweep dorsalward into the fasciculus cinguli. The thalamocingulate projection system remains enclosed in the fasciculus cinguli throughout the latters rostrocaudal extent, continually issuing fibers to the medial cortex, including the presubicular cortex. In comparison to its thalamocortical components the fasciculus cinguli of the rat appears only sparsely populated by corticocortical fibers. Moreover, efferents from the cingulate cortex projecting to subcortical structures do not become enclosed within the fasciculus cinguli, but traverse the bundle and accumulate in a deeper fiber stratum (the internal sagittal stratum of the white matter) from which they penetrate the layer of callosal fibers to join the internal capsule. Of this category of cortical efferents, the corticothalamic fibers originating from the caudal half of the cingulate cortex turn medialward around the stria terminalis and enter the thalamus as components of the lateral thalamic peduncle. The present finding that the thalamocingulate fibers, including the projection to the caudal cingulate region, do not travel by way of the lateral thalamic peduncle reveals a marked contrast in the respective trajectories of the thalamocingulate and cingulothalamic pathways.

The Effects of Haloperidol on Synaptic Patterns in the Rat Striatum

A morphometric analysis of the corpus striatum of rats chronically treated with haloperidol was performed at the light and electron microscopic levels. Although the density of striatal neurons was unchanged in the haloperidol-treated group, there was a small increase in neuronal size (13%). This change in cell size was paralleled by a trend towards larger dendrite calibres occurring in the drug-treated animals. The distribution curve for axon terminal size indicated that 12% of the overall population was shifted from a range with a median size of 0.8 micron 2 to one with 1.6 micron 2 in the drug-treated group. This increase in size of some striatal terminals was accompanied by a concomitant increase in numbers of their associated synaptic vesicles, resulting in a similar density of vesicles for both control and drug-treated animals.

Light microscopic evidence of striatal input to intrapallidal neurons of cholinergic cell group Ch4 in the rat: a study employing the anterograde tracerPhaseolus vulgaris leucoagglutinin (PHA-L)

Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) were placed in various striatal loci in the rat. Within the globus pallidus, PHA-L-filled striatofugal axons were seen to approach cholinergic neurons, identified with either acetylcholinesterase histochemistry or choline acetyltransferase immunohistochemistry, and, apparently, to contact the surface of such cells with axonal varicosities. Since these varicosities are thought to mark the sites of synaptic terminals, such juxtapositions provide strong light-microscopic evidence that intrapallidal cholinergic neurons in the rat receive a direct innervation from the striatum and are integrated into the circuitry of the basal ganglia.

The cytology of dopaminergic and nondopaminergic neurons in the substantia nigra and ventral tegmental area of the rat: A light- and electron-microscopic study

The results of this study support the conclusion that dopaminergic cells can be distinguished from non-dopaminergic cells, at both the light- and electron-microscopic level, by cytological features, and particularly by the pattern of Nissl substance. In both the substantia nigra and the ventral tegmental area, two main categories of cell type can be identified in Nissl preparations: (1) dark-staining, basophilic cells with large masses of Nissl substance and (2) light-staining cells with more translucent cytoplasm. The following findings provide evidence that the basophilic cells of both substantia nigra and ventral tegmental area are the dopaminergic cells. (1) There is a good correlation between the topographic distribution of basophilic cells and that of dopaminergic cells mapped by both histofluorescence and immunohistochemical methods. (2) After unilateral destruction of the dopaminergic neurons by intracerebral injection of 6-hydroxydopamine in the dopaminergic pathway, the basophilic cells in the substantia nigra and ventral tegmental area disappeared on the lesion side, while the lighter-staining cells appeared unaffected. (3) In normal rats, and in rats with unilateral 6-hydroxydopamine lesions, intraventricular injection of [3H]norepinephrine was used for specific labeling of dopaminergic neurons. In autoradiograms of semithin sections, such labeling was observed only in dark-staining and not in light-staining cells, and in cases of unilateral 6-hydroxydopamine lesion was totally absent on the lesion side. Electron-microscopy showed much of the cytoplasm of the basophilic dopaminergic cells to be densely filled with free ribosomes associated with large, well organized complexes of rough endoplasmic reticulum. The cytoplasm of the light, non-dopaminergic cells contains only sparse free ribosomes and small, widely spaced aggregates of rough endoplasmic reticulum. Both cell types occur in a similar variety of size and shape.

Migration and differentiation of ganglion cells in the optic tectum of the chick embryo

Abstract The ganglion cell of the deep gray layer of the tectum is characterized by a large perikaryon and long thick dendrites spreading widely into the overlying intermediate and superficial layers. Its axon projects from the ventral aspect of the soma into the adjacent deep white layer and runs tangentially with the efferent tectal fibers. Migration of the ganglion cell neuroblast from the matrix zone to its definitive location was traced in rapid Golgi preparations from a series of staged embryos. The neuroblast apparently does not begin to migrate until 1–2 days after its last cell division. Initially, the postmitotic neuroblast is an elongated cell, its perikaryon in the matrix zone and primitive external process extending radially through the mantle and marginal zones. Before the cell body migrates, an axon grows out from the external process, thus preventing movement of the cell as a whole. These early-forming axons establish a fiber layer, which is the forerunner of the mantle zone. The migration of the neuroblast is accomplished by elongation of a leading process and translocation of the cell body through the process. A sequence of three stages can be observed in the migration: radial, tangential and oblique. In each of these stages, the corresponding radial, tangential or oblique orientation of the leading process defines the migration route of the cell body. There is no consistent arrangement of supporting cells or neuroglia with respect to these migration routes. After its definitive location in the ganglion cell layer, the young neuron forms dendrites. This remarkable sequence of morphological events is not explained by locomotion of the entire cell or by current notions of cellular guidance of the neuroblast in migration and differentiation. Rather, the results suggest that the factors controlling migration are contemporaneous with, and perhaps the same as, those involved in the growth and elongation of the neuroblast.

Synaptic rearrangements in medial prefrontal cortex of haloperidol-treated rats.

The effects of daily administration of haloperidol for 16 weeks on the structure of layer VI in medial prefrontal cortex of rat was performed at the light and electron microscopic levels. At the light microscopic level, no difference in either the size or the density of neurons was observed. At the electron microscopic level, the mean dendritic calibre of haloperidol-treated rats was twice that observed in control animals, but this was due to a selective loss of small-calibre dendritic profiles. Rats treated with neuroleptic also showed a reduction in axon terminals with asymmetric postsynaptic membrane specializations, which, in control animals, were preferentially associated with small-calibre dendritic profiles. These small-calibre dendritic profiles were found to be spines rather than small terminal dendritic shafts. An increase in axon terminals showing no membrane specialization on larger dendritic profiles also occurred in rats treated daily with the neuroleptic. The data suggest the possibility that haloperidol may have induced a relocation of asymmetric terminals from resorbed spinous processes to larger dendritic branches with the concomitant loss of their postsynaptic membrane specialization.

Neuroanatomical Organization of Dopamine Neurons in the Ventral Tegmental Area

This review will summarize work from our laboratory on several aspects of the neuroanatomical organization of the ventral tegmental area (VTA), namely, shape and volume, the cytology of dopaminergic and nondopaminergic cells,’ and efferent connections,s and conduction lines through the ventral pallidum, thalamus and It is based on evidence from experiments using a variety of techniques such as computer-aided three-dimensional reconstruction, histology, electron microscopy, and anterograde and retrograde neuronal tracing. Three main points will be emphasized: (1) The dopamine cells of the ventral tegmental area lie in a continuum with those of the pars compacta of the substantia nigra. (2) The VTA projects to the nucleus accumbens, and also projects to a region of thestriatum considerably larger than usually recognized, namely to a ventromedial sector of the striatum which extends dorsalward from the nucleus accumbens. This region of the striatum is closely associated with the “limbic” system by the number of afferent projections it receives from the amygdala, medial frontal and cingulate cortex, the thalamus, the VTA, and the raphe nuclei. This “limbic” striatum projects to the ventral pallidum, which in turn projects to these same areas, namely the amygdala, medial frontal and cingulate cortex, the mediodorsal thalamic nucleus, the VTA, and the raphe nuclei. (3) The VTA has multiple projections to these structures of the limbic system by direct projections and by conduction lines through the ventral pallidum and the thalamus.

Regional somatostatin distribution in the rat striatum

Somatostatin-like immunoreactivity (SLI) was detected by a specific radioimmunoassay in extracts from rat striatum. There was a topographic distribution of somatostatin with the highest levels in the nucleus accumbens and ventromedial striatum and the lowest levels in the dorsolateral striatum. This suggests that somatostatin-containing afferents to the striatum may originate from limbic system nuclei which project in a similar distribution. Gel permeation chromatography showed 5 distinct peaks of immunoreactive somatostatin. The two largest peaks coeluted with somatostatin 14 (SS-14) and somatostatin 28 (SS-28) and accounted for 72 and 12% of the total immunoreactivity, respectively. Reversed phase high pressure liquid chromatography confirmed that the majority of immunoreactive material co-chromatographs with SS-14; a smaller amount co-chromatographed with SS-28.

Migration and differentiation of shepherd's crook cells in the optic tectum of the chick embryo

Abstract Shepherds crook cells are a class of neurons with perikarya in the intermediate tectal layers, single or multiple basal dendrites, and long apical dendrites from which the axon arises in the form of a shepherds crook. The axon distinguishes this neuron from all other types, even at early developmental stages. Migration and differentiation of these cells were followed in rapid Golgi preparations from a series of staged embryos and chicks. Since the axon is the first definitive process to appear, even before the cell body completes its migration, it was possible to identify this cell type early in development and to reconstruct certain morphogenetic events that characterize neurogenesis in this class of cells. The postmitotic, migratory neuroblast extends from the outer border of the matrix zone and, by its external, leading process, runs radially through the deep fiber layer into the marginal zone. While the perikaryon is still within the deep fiber layer, the axon appears on the external process in the form of a crook. The crook provides a fixed point of reference within the presumptive intermediate tectal layers during succeeding stages of development. Subsequently, the perikaryon must move up or through its own external process to reach its final location in the intermediate tectal layers. As a result of this mode of migration there often remains a long, thin tail of the trailing, internal process extending back into the deep fiber layer. The definitive apical and basal dendrites appear to develop, respectively, from the remaining portions of the external and internal processes. In the development of the shepherds crook cell there is a strict sequence of morphogenetic changes. Hence, specificity in the nervous system manifests itself not only in the types of neurons formed and their connections, but also in the assembly process itself. However, the exact sequence of the transitions differs for different types of neurons. In the case of the shepherds crook cell, a leading process grows into the mantle zone, followed by the outgrowth of the axon, migration of the perikaryon, and, finally, differentiation of the dendrites. The factors that initiate axonal and dendritic growth seem to be independent of perikaryal location. The perikaryon continues to migrate after axonal outgrowth but never reaches the origin of the axon. We conclude that the migration of the shepherds crook cell takes place by perikaryal translocation through an external, leading process. In the light of these findings, we suggest that the progress of a cells migration can be analyzed with reference to three events: a change in the length of the leading process, a change in the length of the trailing process, and a change in the position of the perikaryon within the cerebral wall. Differences in the rates at which these three events occur could explain the variety of morphological forms assumed by migratory neuroblasts in different parts of the brain.

Changes in cortical and subcortical levels of monoamines and their metabolites following unilateral ventrolateral cortical lesions in the rat

Suction lesions were made in the anterior, posterior or both halves of the right ventrolateral cortex in rats. Six days later, levels of the monoamine neurotransmitters, norepinephrine (NE), dopamine (DA) and serotonin (5-HT), and their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA), were measured in cortical and subcortical regions of lesioned rats and compared to values in sham-operated animals. NE and 5-HT were decreased in sections of ipsilateral (right) cortex including, and posterior to lesions, while 5-HIAA was increased throughout the ipsilateral cortex. Decreases in monoamines and increases in metabolites and metabolite:monoamine ratios (especially 5-HIAA:5-HT) were found in ipsilateral subcortical structures, including striatum, nucleus accumbens, hippocampus, hypothalamus, midbrain and brainstem, depending on the type of lesion. Subacutely, focal ventrolateral cortical lesions may profoundly alter the levels and utilization rates of monoamine neurotransmitters in widespread regions of the ipsilateral hemisphere.