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J H Morrison

Publications and source records attributed to J H Morrison.

At least 163 records · Page 9Linked to original sources

Quantitative morphology and regional and laminar distributions of senile plaques in Alzheimer's disease.

Senile (neuritic) plaques are one of the two major neuropathologic hallmarks of Alzheimer's disease. Despite their obvious importance (e.g., they are significantly correlated with severity of dementia), there is little present information about their etiology, the specific neuronal elements that form them, or a quantitative definition of where in cortex they occur. We have sought clues to these issues by quantifying regional and laminar distributions of neocortical plaques and setting these data against the present wealth of information on neocortical cytoarchitecture and neurotransmitter-specific circuitry. Senile plaques are significantly more numerous in associative regions of neocortex than in sensory areas and are significantly more numerous in cortical laminae dominated by their role in corticocortical, associative relations. Plaques are also largest in those laminae characterized by large pyramidal cells subserving input/output functions. The quantitative distribution of senile plaques in Alzheimer's disease does not necessarily correspond to innervation patterns for any known subcortical afferent system. This, coupled with the finding that several different neurotransmitters can be immunocytochemically co-localized with plaques, casts doubts on a primary role of cholinergic deterioration in plaque etiology, and opens the possibility that neocortical senile plaques may derive from pathologic events initiated in the neocortex.

Alzheimer Disease↗

The serotonin and norepinephrine innervation of primary visual cortex in the cynomolgus monkey (Macaca fascicularis).

The morphology and laminar distribution of norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) axons in the primary visual cortex of cynomolgus monkeys (Macaca fascicularis) have been analyzed by immunocytochemistry with antibodies directed against dopamine-beta-hydroxylase (DBH) and against 5-HT. The NE and 5-HT innervation of primary visual cortex (area 17) in the monkey exhibit highly differentiated laminar patterns. Both of these monoamine axonal systems form tangentially continuous laminar bands that differ in density, morphology, and predominant orientation of constituent fibers. Serotonin axons, present in all cortical layers, form two especially prominent, dense bands of arborizing fibers; one extending from midlayer III through IVC-alpha and the other from VA through VI. NE axons within cynomolgus visual cortex are markedly less dense than 5-HT axons, and laminar differences in NE density are less prominent. NE axons form two broad bands of moderate density extending through deep and superficial cortical layers, separated by layer IVC, which is conspicuously poor in NE fibers. The laminar complementarity of 5-HT and NE innervation that is a notable feature of the squirrel monkey visual cortex is not present in cynomolgus monkey; in this Old World monkey NE and 5-HT axons show considerable overlap such that the same cortical layers appear to be innervated by both neurotransmitters. By virtue of their laminar distribution, 5-HT and NE axons may each have a selective influence on the intrinsic circuitry of primate cerebral cortex, and, for 5-HT in particular, the specific cellular targets of this influence are likely to differ in New and Old World monkeys.

Animals↗

The distribution and morphological characteristics of the intracortical VIP-positive cell: an immunohistochemical analysis.

Using a sensitive immunohistochemical procedure, we have undertaken a detailed morphological characterization of the vasoactive intestinal peptide-positive (VIP-positive) neuron in the cerebral cortex of the rat. VIP-positive neurons are present in all regions of cortex, and are usually strongly bipolar, possessing long, radially directed processes with very limited branching in the tangential plane. The most extensive dendritic branching occurs in layers I and deep IV-superficial V, and the density of axonal varicosities is highest in layers II-IV. In the visual cortex, approximately 50% of the labeled cell bodies are in layer II and III and 80% of the labeled cell bodies are contained in layers I-IV (superficial 600 microns of cortex). In order to determine the density and 3-dimensional distribution pattern of these cells, we prepared serial tangential sections through the rat visual cortex, mapped the distribution of all labeled cells in each section on transparent acetate sheets, and compressed these superimposed maps. This analysis demonstrated that: (1) approximately 1% of the cortical neurons are VIP-positive, (2) their distribution is fairly uniform and statistically random, (3) there are no large areas (i.e. with a diameter greater than 100 microns) that lack a VIP-positive cell, (4) on the average, there is one VIP-positive cell per column of 30 microns diameter, and (5) the average nearest neighbor distance on the compressed display is 15 microns. Given the morphological characteristics of VIP-positive cells, these data indicate that each VIP-containing cell is identified with a unique radial volume, which is generally between 15 and 60 microns in diameter, and overlaps with the contiguous domains of neighboring VIP-positive cells. These morphological data support the notion that VIP-containing neurons play an important functional role within radially oriented columns of cerebral cortex.

Animals↗

Evidence for selective release of somatostatin-14 and somatostatin-28(1-12) from rat hypothalamus.

Cysteamine administration to rats results in a marked depletion of hypothalamic somatostatin-14 (SS14) and a decrease of the potassium-evoked in vitro release of SS14 without a significant change in the content or release of somatostatin-28(1-12)-like immunoreactivity (SS28(1-12)-L1). Furthermore, cysteamine enhances the spontaneous release and markedly potentiates the potassium-evoked release of SS14 in the in vitro slice preparation. However, in vitro-administered cysteamine does not alter the spontaneous or potassium-evoked release of SS28(1-12)-LI. Immunohistochemical visualization of hypothalamic neuronal cell bodies and fibers following cysteamine administration shows a disappearance of the SS14 immunoreactive fibers and cell bodies with no apparent change in the SS28(1-12) immunoreactive fibers and cell bodies. These data suggest that, in rat hypothalamus, selective release of SS14 and SS28(1-12) can occur. The results are discussed in relation to possible sites of storage and release of the somatostatin-related peptides from synaptic nerve terminals.

Animals↗

Postnatal development of laminar innervation patterns by monoaminergic fibers in monkey (Macaca fascicularis) primary visual cortex.

Immunohistochemical methods are used to characterize the distribution of noradrenergic and serotonergic fibers in primary visual cortex of cynomolgus monkeys (Macaca fascicularis) at various postnatal ages. Previous studies in adult squirrel monkeys have shown that serotonergic fibers are generally restricted to the upper four cortical laminae and are especially dense in layer IV, whereas noradrenergic fibers are especially dense in layers V and VI, moderate in layers I, II, and III, and virtually absent in layer IV (Morrison, J. H., S. L. Foote, M. E. Molliver, F. E. Bloom, and H. G. W. Lidov (1982) Proc. Natl. Acad. Sci. U.S.A. 2401-2405; Morrison, J. H., S. L. Foote, D. O'Connor, and F. E. Bloom (1982) Brain Res. Bull. 9: 309-319). Since these monoamines, especially norepinephrine, have been hypothesized to play an essential role in the developmental plasticity of visual cortex organization (e.g., Kasamatsu, T., and J. D. Pettigrew (1976) Science 194: 206-209; Pettigrew, J. D., and T. Kasamatsu (1978) Nature 271: 761-763), the present study examined the postnatal development of these innervation patterns, especially just before and just after the reported "critical period" for visual plasticity. A dense serotonergic innervation of layer IV is present at birth along with sparse innervation of other laminae. The adult pattern of serotonergic innervation, which is similar to that in the squirrel monkey but even more specifically laminated, becomes evident by 6 weeks of age. In the adult pattern, the most dense innervation remains in layers IVb and IVc. A much lower density of noradrenergic than of serotonergic fibers is evident at all ages examined. As with serotonin, the lowest density of fibers is observed at birth. By about 2 months of age these noradrenergic fibers have become more dense, and their laminar distribution is similar to that of adult cynomolgus which is similar to adult squirrel monkey. These studies indicate that: (1) both types of innervation display a continuum of development, with no abrupt changes, (2) serotonergic innervation is more dense than noradrenergic innervation at every age examined, (3) these two transmitter systems exhibit very different laminar innervation patterns as early as birth, and (4) the greater laminar specialization of area 17 in cynomolgus versus squirrel monkeys is accompanied by corresponding enhanced laminar specialization of these monoaminergic afferents.

Aging↗

Loss of pigmented dopamine-beta-hydroxylase positive cells from locus coeruleus in senile dementia of Alzheimer's type.

Serial sections of human brainstem were used to determine the total number of pigmented cells in locus coeruleus and, by immunohistochemical staining using an antiserum directed against human dopamine-beta-hydroxylase (DBH), the number of DBH-positive cells. In 12 brains from elderly control and dementia subjects there wer not significant differences in the total cell populations determined in the same brain by the two techniques. In 6 patients with senile dementia of Alzheimer's type there was a variable loss (average about 60% reduction) in locus coeruleus cells when compared to controls of similar age. The loss of noradrenergic neurones from locus coeruleus was accompanied by an average reduction of similar magnitude in noradrenaline concentration in temporal cortex, with no change or an increase in dopamine content. There was also a significant reduction in the cholinergic marker choline acetyltransferase in cortex samples from the dementia cases.

Aged↗

Immunohistochemical distribution of pro-somatostatin-related peptides in cerebral cortex.

Mammalian brain contains 3 peptides related to the pro-somatostatin molecule: somatostatin-14 (SS14), the form originally identified from hypothalamic extracts, somatostatin-28 (SS28) and somatostatin 28 (1-12) (SS28 (1-12)). By using antibodies which selectively recognize one or more of these 3 somatostatin-related peptides, we have characterized their immunohistochemical distribution in neocortex. These somatostatin-related peptides have a specific laminar distribution in cortex and are differentially distributed such that SS28 is largely restricted to cell bodies, whereas SS28 (1-12) is preferentially localized in neuronal processes and terminals in a density which far exceeds that revealed by SS-14 immunoreactivity. These data suggest that there may be an intraneuronal transformation from a SS28-like peptide to a SS28 (1-12)-like peptide. In addition, the enriched distribution of nerve fibers containing the antigenic determinant, SS28 (1-12), strongly implies that somatostatin-related peptides constitute a major neurotransmitter system in neocortex. The morphological characteristics of this system are homologous with long projection pathways such as the cortico-cortical specific intrinsic systems as well as projections.

Animals↗

Effect of 6-hydroxydopamine lesions on norepinephrine-induced [3H]glycogen hydrolysis in mouse cortical slices.

The effects of norepinephrine (NE) on in vitro [3H]glycogenolysis were assessed in slices of cerebral cortex from mice whose cortical noradrenergic innervation had been severely reduced by intracisternal 6-hydroxydopamine (6-OHDA) injections. A supersensitive response to NE was observed, as demonstrated by a decrease in the EC50 of the catecholamine in the lesioned mice from 533 +/- 88 nM to 39.3 +/- 7.9 nM. This supersensitive response, observed two weeks after the lesion, was post-synaptic since isoproterenol, a beta-adrenergic agonist not accumulated by pre-synaptic uptake mechanisms, also gave an equally supersensitive response.

Adrenergic Fibers↗

Immunohistochemical distribution of pro-somatostatin-related peptides in hippocampus.

By using immune sera which recognize one or more of the 3 peptides, somatostatin-14 (SS14), somatostatin-28 (SS28) and somatostatin-28(1-12) (SS28(1-12)) we have characterized their immunohistochemical distribution in the hippocampal formation. There exist at least two independent neuronal systems containing pro-somatostatin-related peptides: an intrinsic system of cells in the polymorphic layers which branch locally, and a dense terminal field in the molecular layer of the dentate gyrus that may constitute a portion of the entorhinal-dentate projection. In addition, SS28 is the dominant form present in cell bodies, whereas SS28(1-12) is preferentially localized in neuronal processes and terminals. We could not detect SS14 immunohistochemically.

Animals↗

Noradrenergic and serotonergic fibers innervate complementary layers in monkey primary visual cortex: an immunohistochemical study.

Antisera directed against human dopamine beta-hydroxylase or serotonin were used to characterize the noradrenergic and serotonergic innervation patterns within the primary visual cortex of the squirrel monkey. The noradrenergic and serotonergic projections exhibit a high degree of laminar complementarity: layers V and VI receive a dense noradrenergic projection and a very sparse serotonergic projection, whereas layer IV receives a very dense serotonergic projection and is largely devoid of noradrenergic fibers. In addition, the noradrenergic fibers manifest a geometric order that is not so readily apparent in the distribution of serotonergic fibers. These patterns of innervation imply that the two transmitter systems affect different stages of cortical information processing--the raphe-cortical serotonergic projection preferentially innervates the spiny stellate cells of layers IVa and IVc, whereas the ceruleo-cortical noradrenergic projection innervates pyramidal cells.

Animals↗

Somatostatin-28(1-12)-like immunoreactivity in the rat.

The distribution of the newly characterized peptide somatostatin-28(1-12) was determined in rat tissues using a radioimmunoassay in which the immune plasma is directed against the C-terminus of the dodecapeptide. In the central nervous system, somatostatin-28(1-12)-like immunoreactivity is highly concentrated in the hypothalamus and the amygdala. In the digestive system, the highest levels of immunoreactivity are found in the stomach, the pancreas and the colon. The immunoreactive material measured in different tissues is the heterogenous: in addition to the dodecapeptide, two N-terminally extended somatostatin-28(1-12) peptides of 4,400 and 8,000 mol wt are also detected by the immune plasma. However, the dodecapeptide itself usually accounts for the majority (66 to 75%) of the total somatostatin-28(1-12)-like immunoreactivity present in those tissues.

Animals↗

Vasoactive intestinal polypeptide induces glycogenolysis in mouse cortical slices: a possible regulatory mechanism for the local control of energy metabolism.

Mouse cerebral cortex slices will synthesize [3H]glycogen in vitro. Vasoactive intestinal polypeptide (VIP) stimulates the enzymatic breakdown of this [3H]glycogen. The concentration giving 50% of maximum effectiveness (EC50) is 26 nM. Under the same experimental conditions norepinephrine also induces a concentration-dependent [3H]glycogen hydrolysis with an EC50 of 500 nM. The effect of VIP is not mediated by the release of norepinephrine because it is not blocked by the noradrenergic antagonist d-1-propranolol and is still present in mice in which an 85% depletion of norepinephrine was induced by intracisternal 6-hydroxydopamine injections. Other cortical putative neurotransmitters such as gamma-aminobutyric acid, aspartic acid, glutamic acid, somatostatin, and acetylcholine (tested with the agonist carbamylcholine) do not induce a breakdown of [3H]glycogen. This glycogenolytic effect of VIP and norepinephrine, presumed to be mediated by cyclic AMP formation, should result, at the cellular level, in an increased glucose availability for the generation of phosphate-bound energy. Given the narrow radial pattern of arborization of the intracortical VIP neuron and the tangential intracortical trajectory of the noradrenergic fibers, these two systems may function in a complementary fashion: VIP regulating energy metabolism locally, within individual columnar modules, and norepinephrine exerting a more global effect that spans adjacent columns.

Animals↗

Noradrenergic innervation of cerebral cortex: widespread effects of local cortical lesions.

The trajectory of the intracortical noradrenergic fibers has been characterized by histochemical analysis following the production of cortical lesions in the rate. A large group of noradrenergic fibers enters the cortex at the frontal pole and proceeds caudally through the deep layers of dorsolateral cortex. Branches arise from these longitudinally directed fibers and form a uniform pattern of innervation throughout lateral cortex. Because these fibers travel long distances rostrocaudally within the gray matter, a large area of cortex can be deprived of noradrenergic innervation by a relatively small lesion of frontal cortex. The medial and lateral cortex can be selectively and differentially denervated of noradrenergic fibers, and there is a medial to lateral topographic relationship between deep longitudinally running fibers and overlying cortex.

Animals↗

Alterations in consummatory behavior of mice produced by dietary exposure to inorganic lead.

Mice suckled by mothers given tap water and by mothers given a 5 mg/ml lead acetate solution during lactation were given a choice between tap water and a lead acetate solution after lactation. All offspring demonstrated an immediate aversion to the lead acetate solution. The offspring from the mothers receiving lead acetate during lactation demonstrated a greater aversion to the lead acetate solution than did the offspring from mothers receiving tap water. In addition, the lead acetate offspring drank more total fluid (tap water plus lead acetate solution) after weaning than the control offspring. The results indicate both learned and unlearned changes in motivation for fluid following ingestion of lead via the mother's milk in infancy.

Animals↗