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V B Domesick

Publications and source records attributed to V B Domesick.

At least 19 recordsLinked to original sources

Morphological assessment of neuronal aggregates in the striatum of the rat.

Regional variations in cell-packing density, culminating in the formation of cell clusters, is now a recognized morphological characteristic of the striatum that has been correlated, in some instances, with either regional histochemical variations or the distribution pattern of afferent fiber systems, or both. Within these cluster regions a further level of organization exists, in the form of discrete neuronal aggregates. The light microscopic morphology of these neurons and the nature of their intercellular contacts at the electron microscope level form the focus of this report. The neurons composing such aggregates are characterized by contiguous soma-somatic or soma-dendritic contact with extended regions of junctionlike symmetrical and consistent contacts where the distance between the cytoplasmic membranes of apposing neurons narrows to as close as 7 nm. Coated vesicles close to the contact areas are common. Three-dimensional computer reconstructions of serial 1 micron sections through aggregates in either the caudatoputamen or nucleus accumbens reveal "chains" of contiguous cells that frequently involve as many as 60 neurons. These contiguous cell aggregates are discrete entities within the larger clusters or islands. It is postulated that the cellular aggregates may represent the fundamental level of striatal organization and may be local modules for intrinsic information processing, modifying extrinsic data processed through the biochemical compartmentalization of the striatum imparted by striosomes, neuropeptides, and dopaminergic, thalamic and cortical afferents.

Animals↗

Light microscopic evidence of striatal input to intrapallidal neurons of cholinergic cell group Ch4 in the rat: a study employing the anterograde tracer Phaseolus 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.

Acetylcholinesterase↗

The visual cortico-striato-nigral pathway in the rat.

The organization of the visual cortico-striato-nigral pathway in the rat has been investigated in two sets of experiments using anterograde autoradiographic tracing techniques. First, in one group of animals, injections of tritiated amino acids were placed throughout the visual cortex to demonstrate the visual corticostriatal pathway. The results indicate that visual corticostriatal fibres terminate in a distinctive clustered pattern throughout the entire length of the ipsilateral dorsomedial striatum. The projection shows a longitudinal topographic organization with cortical loci projecting onto narrow longitudinal regions of the dorsomedial striatum. In addition to the ipsilateral projection, a substantially smaller contralateral visual corticostriatal projection was also demonstrated. In the second set of experiments, the visual corticorecipient region of the striatum demonstrated in the first set of experiments was injected with tritiated amino acids to demonstrate the "visual" striatonigral projection. The results indicate that striatonigral fibres from the dorsomedial striatum project throughout the rostrocaudal extent of the ventral region of the pars reticulata. As with the visual corticostriatal pathway, the projection shows a longitudinal topographic organization with striatal loci projecting onto longitudinal regions of the ventral pars reticulata; the most rostral regions of the dorsal striatum project to the most medial regions of the ventral pars reticulata and, likewise, successively more caudal regions of the dorsal striatum project to successively more lateral regions of the ventral pars reticulata. In addition to the main projection to the ventral pars reticulata, a second smaller component of the striatonigral pathway was traced to adjacent regions of the dorsal pars reticulata and ventral pars compacta. These findings provide evidence of a visual cortico-striato-nigral pathway to both the pars reticulata and pars compacta in the rat. It is suggested that the major projection onto the ventral pars reticulata may provide an input onto nigrotectal neurons and thereby complete an indirect visual corticotectal connection mediated via links in the basal ganglia.

Animals↗

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.

Animals↗

Effects of lesions in the amygdala and periventricular hypothalamus on striatal somatostatin-like immunoreactivity.

Somatostatin has been found in substantial amounts in the basal ganglia by radioimmunoassay and has been demonstrated in both neurons and nerve terminals. Since the levels of somatostatin have been shown to vary in Huntington's and Alzheimer's disease it was of interest to see whether such changes could be produced experimentally. Lesions of the periventricular nucleus of the hypothalamus and knife cuts adjacent to this nucleus had no effect on striatal somatostatin-like immunoreactivity (SLI). Similarly lesions of medio-dorsal frontal cortex, and those isolating pyriform cortex or the olfactory bulb had no effect on striatal SLI. Removal of the amygdala resulted in significant increases in SLI in the ipsilateral striatum and nucleus accumbens, suggesting loss of an inhibitory interaction. Stria terminalis lesions failed to reproduce this effect suggesting that it is mediated via amygdalo-striatal projections traveling in the dorsal longitudinal bundle. Other findings support a somatostatin projection to the amygdala from the bed nucleus of the stria terminalis and one from the amygdala to the ventromedial hypothalamus.

Amygdala↗

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.

Animals↗

Afferent and efferent relationships of the basal ganglia.

A survey of the known circuitry of the basal ganglia leads to the following conclusions. (1) No complete account can yet be given of the neural pathways by which the basal ganglia affect the bulbospinal motor apparatus. Channels of exit from the basal ganglia originate from the internal pallidal segment, the pars reticulata of the substantia nigra, and the subthalamic nucleus, and each of these is directed in part rostrally to the cerebral cortex by way of the thalamus, in part caudally to the midbrain. The postsynaptic extension of the mesencephalic channels to bulbar and spinal motor neurons is largely unknown. Since the ascending channels are collectively of greatest volume, the notion remains plausible that the basal ganglia act in considerable part by modulating motor mechanisms of the cortex. (2) Recent findings in the rat suggest that the striatum is subdivided into a ventromedial, limbic system-afferented region and a dorsolateral, 'non-limbic' region largely corresponding to the main distribution of corticostriatal fibres from the motor cortex. These two subdivisions appear to give rise to different striatofugal lines, the outflow from the limbic-afferented sector partly re-entering the circuitry of the limbic system. (3) The limbic-afferented striatal sector suggests itself as an interface between the motivational and the more strictly motor aspects of movement. This suggestion is strengthened by evidence that the 'limbic striatum' seems enabled by its striatonigral efferents to modulate not only the source of its own dopamine innervation but also that of a large additional striatal region.

Animals↗

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.

Animals↗

Haloperidol-induced plasticity of axon terminals in rat substantia nigra.

An electron micrographic morphometric analysis of nerve endings in substantia nigra of rats repeatedly treated with haloperidol was performed. Although most parameters showed no difference, drug-treated animals exhibited a significant shift in the distribution of relative numbers of axon terminals, suggesting neuroleptic-induced axon-collateral sprouting.

Animals↗

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.

3,4-Dihydroxyphenylacetic Acid↗

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.

Animals↗

The amygdalostriatal projection in the rat--an anatomical study by anterograde and retrograde tracing methods.

Tritiated leucine and proline injected into the amygdaloid complex was found to label a voluminous amygdalostriatal fiber system which is distributed to all parts of the striatum except an antero-dorsolateral striatal sector. The connection is established by way of the longitudinal association bundle as well as the stria terminalis, and includes a modest (10-15%), symmetrically distributed contralateral component conveyed by the anterior commissure. Both autoradiographic findings and subsequent observations in retrograde cell-labelling (horseradish peroxidase) material indicate that the amygdalostriatal projection originates mainly from the nucleus basalis lateralis amygdalae, in much lesser volume from the nucleus basalis medialis, and minimally from the nucleus lateralis amygdalae; no other contributing amygdaloid cell group could be identified. A comparison of the present findings with earlier reports indicates that the amygdalostriatal projection widely overlaps the striatal projections from the ventral tegmental area, the mesencephalic raphe nuclei and the prefrontal cortex. Like the amygdalostriatal projection, these striatal afferents largely or entirely avoid the antero-dorsolateral striatal quadrant, which thus appears to be the striatal region most sparsely innervated by afferents originating from structures within the circuitry of the limbic system. Findings in additional autoradiographic material identify this relatively non-limbic striatal quadrant as the main region of distribution of the corticostriatal projection from the sensorimotor cortex.

Afferent Pathways↗

The distribution of the projection from the hippocampal formation to the nucleus accumbens in the rat: an anterograde- and retrograde-horseradish peroxidase study.

We have investigated the distribution and organization of the projection from the hippocampal formation to the nucleus accumbens in the rat. In the first experiments, horseradish peroxidase was injected into the fimbria fornicis. This procedure resulted in massive anterograde labelling of fornix fibers, and enabled the hippocampo--accumbens projection to be charted in detail. Labelled fornix fibers are distributed to the entire length of the nucleus accumbens and do not spread lateral to the anterior limb of the anterior commissure, that is, the projection is limited to the medial nucleus accumbens. Terminal labelling is particularly dense in a caudal dorsomedial sector of accumbens immediately adjacent to the septum. In the second part of the study, horseradish peroxidase was microelectrophoretically injected into the nucleus accumbens, in order to confirm the findings from the anterograde experiments. When the deposit was localized within the fornix distribution field, as indicated by the first experiment, retrogradely-labelled cells were observed in the subiculum, prosubiculum, and to a lesser extent, in hippocampal field CAI. When the deposit was located outside of the fornix distribution field, no hippocampal labelling was noted. The topography of the projection, suggested by the retrograde labelling experiments, is discussed. The findings confirm earlier reports of such a projection from the hippocampal formation to the nucleus accumbens, and with the use of a relatively novel anterograde-horseradish peroxidase technique, provide a picture of fiber labelling representing the entire field of origin of the fornix system. The striatal projection field of this pathway is discussed in relation to other striatal afferents, with particular emphasis on limbic afferentation of the striatum. Finally, the so-called 'hippocampal district' of striatum is discussed with respect to its neurotransmitter composition, as well as its functional importance regarding limbic system influence on central motor mechanisms.

Animals↗

Attention and habituation: odor preferences, long-term memory, and multiple sensory cues of novel stimuli.

Investigation of and habituation to novel stimuli are part of exploratory behavior of rodents. They are necessary for assessing the environment in seeking food and sexual partners and in avoiding predators. Male and female gerbils were tested in the stimulus-elicited investigation paradigm in order to address several questions on three issues: (a) Gerbils initially showed preferences for odors of strange male bedding and for odors of home cage bedding and then habituated. There was no preference between these two odors, although they could be discriminated. The complex odor stimulus elicited more response than any of the components tested. (b) Memory of an object or of an odor was demonstrated up to 4 wk later. (c) Sensory deprivation by blinding, anosmizing, or removing somatosensation of the upper snout made only small differences in investigation. The removal of any two of these sensory inputs produced more interference with the response, but all of the gerbils investigated the stimulus. It is concluded that attention to novelty and habituation after repeated exposure are very robust behaviors and are mediated through multiple sensory channels.

Animals↗

Efferent connections of the substantia nigra and ventral tegmental area in the rat.

Small injections of tritiated leucine and proline confined to the ventral tegmental area (AVT) were found to label fibers ascending: (a) to the entire ventromedial half of the striatum, but most massively to the ventral striatal zone that includes the nucleus accumbens; (b) to the thalamus: lateral habenular nucleus, nuclei reuniens and centralis medius, and the most medial zone of the mediodorsal nucleus; (c) to the posterior hypothalamic nucleus and possibly the lateral hypothalamic and preoptic region; (d) to the nuclei amygdalae centralis, lateralis and medialis; (e) to the bed nucleus of the stria terminalis, the nucleus of the diagonal band, and the medial half of the lateral septal nucleus; (f) to the anteromedial (frontocingulate) cortex; and (g) to the entorhinal area. Further AVT efferents descend to the medial half of the midbrain tegmentum including an anterior region of the median raphe nucleus, to the ventral half of the central grey substance including the dorsal raphe nucleus, to the parabrachial nuclei, and to the locus coeruleus. Similar injections centered in the pars compacta of the substantia nigra (SNC) label fibers that are distributed in the striatum in an orderly medial-to-lateral arrangement, and almost entirely avoid the nucleus accumbens and olfactory tubercle. With the exception of the lateral quarter of the substantia nigra, which apparently does not project to the extreme rostral pole of the striatum, each small SNC locus, regardless of its anteroposterior localization, distributes nigrostriatal fibers throughout the length of the striatum. Descending SNC efferents are distributed to the same general regions that receive descending AVT projections, except that no SNC fibers appear to enter the locus coeruleus. Isotope injections confined to the pars reticulata (SNR) label sparse nigrostriatal fibers, and numerous nigrothalamic fibers ascending mainly to the nucleus ventromedialis and in lesser number to the parafascicular nucleus and the paralamellar zone of the nucleus mediodorsalis. Descending SNR fibers leave the nigra as a voluminous fiber bundle that bifurcates into a large nigrotectal and a smaller nigrotegmental component, the latter terminating largely in the pedunculopontine nucleus of the pontomesencephalic tegmentum.

Amygdala↗