Biomedical subjects

J H Morrison

Publications and source records attributed to J H Morrison.

At least 19 recordsLinked to original sources

PubMed1992

Localization of preprogalanin mRNA in the monkey hippocampal formation.

The existence of neurons expressing preprogalanin mRNA in the monkey hippocampal formation was demonstrated using in situ hybridization of a radio-labelled cRNA probe transcribed from human preprogalanin cDNA. Specific hybridization occurred in neurons of the hilus of the dentate gyrus, fields CA1-3 in Ammon's horn, subiculum, presubiculum, parasubiculum and occasionally in neurons of the entorhinal cortex. These findings suggest that galanin is synthesized by neurons intrinsic to the monkey hippocampal formation.

Animals↗

PubMed1992

Progressive transformation of the cytoskeleton associated with normal aging and Alzheimer's disease.

Transitional and end-stage forms of neurofibrillary tangles associated with normal aging and Alzheimer's disease were identified using thioflavine staining combined with tau and neurofilament protein immunofluorescence. Normal aging was marked by transitional pathology in layer II of the entorhinal cortex but no neurofibrillary tangles in prefrontal cortex, whereas, in Alzheimer's disease cases, layer II entorhinal neurons had progressed to end-stage neurofibrillary tangles and the prefrontal cortex contained a high representation of transitional forms of the neurofibrillary tangle.

Adolescent↗

PubMed1992

The primary auditory cortex in cetacean and human brain: a comparative analysis of neurofilament protein-containing pyramidal neurons.

To extend our investigation of the anatomy of sensory systems in highly adapted aquatic and terrestrial mammals, we have analyzed the distribution of a particular population of efferent neurons in the cetacean and human primary auditory cortex using an antibody to non-phosphorylated neurofilament protein (SMI32). The neurofilament protein triplet is differentially distributed within neuronal subpopulations in the primate and cetacean neocortex. In primates, it appears that the somatodendritic domain of a subset of pyramidal neurons furnishing specific corticocortical connections contains high concentrations of neurofilament protein. In the human primary auditory cortex these neurons are located in layers III, V and VI, whereas in cetaceans they are concentrated almost exclusively in the cortical efferent layer IIIc/V. Previous analyses have shown that SMI32 immunoreactivity in the cetacean neocortex is uniformly distributed among functionally different areas, while in human neocortex, the distribution of SMI32-positive neurons exhibit a high degree of regional and laminar specialization that is correlated with the functional and anatomical diversity of the cortical areas. In addition, the overall distribution of SMI32-immunoreactive neurons in the cetacean neocortex is comparable to that observed in paralimbic areas of the human, suggesting that the cetacean neocortex has retained many features of phylogenetically older cortical regions.

Animals↗

PubMed1992

Evidence for early vulnerability of the medial and inferior aspects of the temporal lobe in an 82-year-old patient with preclinical signs of dementia. Regional and laminar distribution of neurofibrillary tangles and senile plaques.

Detailed neuropathologic studies of neurofibrillary tangle and senile plaque distribution have shown that key elements of certain neocortical and hippocampal circuits are either compromised or lost in Alzheimer's disease. It has been suggested that a global corticocortical disconnection underlies dementia and leads to the dramatic disruption of integrated functions exhibited by patients with Alzheimer's disease. To investigate the distribution of lesions associated with the earliest indications of incipient dementia, we performed a quantitative neuropathologic evaluation of a non-demented 82-year-old patient demonstrating globally intact intellectual function but initial signs of impairment of specific cognitive functions before death. We observed densities of senile plaques comparable to those found in Alzheimer's disease throughout the cerebral cortex, whereas extensive neurofibrillary tangle formation was restricted to selective areas of the temporal lobe. The results of this systematic quantitative and comparative analysis of medial and inferior temporal lobe structures suggest a functional relationship between the degree of cognitive decline evidenced in the earliest stages of Alzheimer's disease and the anatomic progression of Alzheimer's disease-related pathologic changes along specific elements of the cortical circuitry.

Aged↗

PubMed1992

Differential distribution of neurofibrillary tangles in the cerebral cortex of dementia pugilistica and Alzheimer's disease cases.

Head trauma has been associated with the occurrence of Alzheimer's disease and plays a clear role in the etiopathogenesis of the boxers encephalopathy referred to as dementia pugilistica. Neurofibrillary tangles (NFT), one of the pathological hallmarks of Alzheimer's disease are observed in very high densities in the brains of former professional boxers suffering from dementia pugilistica. In Alzheimer's disease, NFT display striking regional and laminar distribution patterns that have been correlated with the localization of neurons forming specific corticocortical connections. In dementia pugilistica cases, NFT were concentrated in the superficial layers in the neocortex, whereas in Alzheimer's disease they predominated in the deep layers. Thus, the association cortex of brains from dementia pugilistica patients demonstrated an inverse NFT distribution as compared to Alzheimer's disease. This finding suggests that a more circumscribed population of cortical pyramidal neurons might be affected in dementia pugilistica than in Alzheimer's disease.

Aged↗

PubMed1992

Localization of multiple dopamine receptor subtype mRNAs in human and monkey motor cortex and striatum.

Dopamine plays a critical role in motor and cognitive function through actions mediated by specific receptors, multiple subtypes of which have recently been identified. The distribution of mRNAs encoding D1, D2 and D5 receptors in the motor cortex of humans and in the motor cortex and striatum of macaque monkeys was examined using in situ hybridization. In motor cortices from both primate species, hybridization to each receptor probe resulted in numerous labeled cells throughout layers II-VI. In contrast to neocortex, in monkey striatum only the D1 and D2 receptor probes showed significant hybridization. Thus, not only does primate neocortex possess a broader representation of the dopamine receptor subtype mRNAs examined in comparison with striatum, but the unexpected presence and widespread distribution of D2 and D5 receptor mRNAs in cortex suggests that, along with D1 receptors, D2 and D5 receptors play a crucial role in the dopaminergic modulation of cognition and motor behavior, and in dopamine dysfunction associated with neuropsychiatric disorders.

Aged↗

PubMed1992

Immunohistochemical identification of thrombospondin in normal human brain and in Alzheimer's disease.

Thrombospondin is part of a family of adhesive glycoproteins and is involved in a number of physiologic processes such as angiogenesis and neurite outgrowth. Immunohistochemical localization of thrombospondin in normal human brains was investigated in the hippocampus and inferior temporal cortex. Two antibodies (one polyclonal and one monoclonal) against thrombospondin-labeled microvessels, glial cells, and a subpopulation of pyramidal neurons. The distribution of thrombospondin staining in patients with Alzheimer's disease was found to be comparable to control subjects. However, in patients with Alzheimer's disease a subset of pyramidal neurons that may be vulnerable in Alzheimer's disease exhibited decreased staining. This decrease in the intensity of labeling might constitute a marker for a neuronal population prone to early degeneration. In addition, thrombospondin staining was demonstrated in senile plaques in Alzheimer's disease. These results suggest that thrombospondin may be involved in the process of neuronal degeneration and senile plaque formation.

Aged↗

PubMed1991

Neurofibrillary tangle distribution in the cerebral cortex of parkinsonism-dementia cases from Guam: differences with Alzheimer's disease.

Parkinsonism-dementia together with amyotrophic lateral sclerosis is a highly prevalent disorder among the native Chamorro population of Guam and is accompanied by severe widespread neurofibrillary tangle formation. In the present study we compared the regional and laminar distribution of neurofibrillary tangles in the cerebral cortex of 5 Guamanian parkinsonism-dementia cases to 9 Caucasian Alzheimer's disease cases. Although in both diseases the superior frontal and inferior temporal cortex were affected to a comparable degree, there was a striking difference in the laminar distribution of neurofibrillary tangles. Neurofibrillary tangles in Alzheimer's disease are known to be more numerous in layers V-VI than in layers II-III of frontal and temporal cortex, however in the Guam cases, the opposite distribution was observed with most of the tangles located within layer II and the superior part of layer III and relatively low tangle density in layers V-VI. Interestingly, in both conditions, the hippocampal pyramidal layer showed a comparable degree of degeneration. Moreover no amyloid deposits and neuritic plaques were observed in the Guam brains, whereas they were frequent in the Alzheimer's disease cases. Previous studies have suggested that the clinical symptomatology observed in patients suffering from Alzheimer's disease is related to the dramatic loss of specific corticocortically projecting neurons in the neocortex. The present data on Guam parkinsonism-dementia further support this hypothesis, although the set of corticocortical connections affected in Guam cases might differ from that observed in Alzheimer's disease, which may contribute to some extent to the different clinical symptoms of the dementia observed in Guamanian patients.

Aged↗

PubMed1991

Parvalbumin in the monkey striate cortex: a quantitative immunoelectron-microscopy study.

Parvalbumin (PV) is present in a subpopulation of interneurons in the visual cortex, and also in thalamic afferents to the neocortex of primates. The object of this study is to confirm by immunoelectron-microscopy the presence of intrinsic and extrinsic connections containing parvalbumin in the monkey visual cortex, by the demonstration of parvalbumin-immunoreactivity in symmetric and asymmetric synapses. We analyzed the distribution of parvalbumin-immunoreactive profiles at the ultrastructural level in the primary visual cortex of old world monkeys (Macaca fascicularis). It has been shown by others that parvalbumin-immunoreactive cells resemble non-spiny stellate cells, double-bouquet cells, chandelier and basket cells. These neurons are known to be inhibitory and to form symmetric synapses. In fact, we observed that the vast majority of parvalbumin-immunoreactive synaptic contacts in the primary visual cortex of Macaca fascicularis are of the symmetric type (81.7%). Since parvalbumin-positive asymmetric contacts are also present (18.3%) and occur mostly in the thalamic recipient layers, 4C and 4A (9.9%), these afferents probably derive from parvalbumin-immunoreactive neurons located in the dorsal lateral geniculate nucleus of the thalamus.

Animals↗

PubMed1991

A subpopulation of primate corticocortical neurons is distinguished by somatodendritic distribution of neurofilament protein.

In recent immunohistochemical studies of human and monkey neocortex we observed that the somatodendritic distribution of neurofilament protein appears to be restricted to a subpopulation of pyramidal neurons. To further characterize this apparent specificity in cytoskeletal organization, combined retrograde tract tracing and immunohistochemical methods were used to examine the extent to which neurons from different cortical areas providing a projection to prefrontal cortex have a somatodendritic distribution of neurofilament proteins. These studies revealed that the proportion of neurons providing a projection from different cortical areas to prefrontal cortex varied from nearly 30% to 90%, and appeared to be related to the functional nature of the projection.

Amidines↗

PubMed1991

Neocortical neuronal subpopulations labeled by a monoclonal antibody to calbindin exhibit differential vulnerability in Alzheimer's disease.

Numerous studies have demonstrated that specific neuronal subtypes display a differential vulnerability to the pathological process in Alzheimer's disease. Large pyramidal neurons are likely to be highly vulnerable, whereas smaller neurons are more resistant to pathology. Using a monoclonal antibody to the calcium-binding protein calbindin, we observed in the human prefrontal cortex distinct populations of labeled cells. First, a subset of heavily stained interneurons was located in layers II and superficial III and in layers V-VI. Second, a subpopulation of pyramidal neurons in the mid and deep parts of layer III displayed a less intense, punctate staining pattern. The interneurons in the superficial layers were unaffected in the Alzheimer's disease cases. Interestingly, in layers V-VI, there was significant cell loss in the interneuron population, but only in the Alzheimer's disease cases with high neurofibrillary tangle densities. The calbindin-immunoreactive pyramidal neurons of layer III were dramatically affected in the disease. Moreover, there was a strong correlation between the extent of the loss of these cells and neurofibrillary tangle counts. These data suggest that calbindin is present in multiple neuronal subpopulations that exhibit a differential vulnerability in Alzheimer's disease and support the hypothesis that the degenerative process involves specific neuronal subsets with particular anatomical and molecular profiles.

Aged↗

PubMed1991

Parvalbumin-immunoreactive neurons in the neocortex are resistant to degeneration in Alzheimer's disease.

Recent studies have stressed the fact that specific neuronal subtypes may display a differential sensitivity to degeneration in Alzheimer's disease. For example, large pyramidal neurons have been shown to be vulnerable, whereas smaller neurons are resistant to pathology. Using a monoclonal antibody against the calcium-binding protein parvalbumin, we investigated the possible changes in a subpopulation of interneurons in two cortical areas known to be strongly damaged in Alzheimer's disease. In the prefrontal cortex as well as in the inferior temporal cortex, we observed no differences in parvalbumin-immunoreactive cell counts or cell size in Alzheimer's disease brains as compared to control cases. Moreover, the general cellular morphology of these neurons was preserved in the Alzheimer's disease cases, in that their perikarya and dendritic arborizations were intact. These results suggest that paravalbumin-immunoreactive cells represent a neuronal subset resistant to degeneration, and further support the hypothesis that the pathological process in Alzheimer's disease involves specific neuronal subtypes with particular morphological and molecular characteristics.

Aged↗

PubMed1991

An anatomic substrate for visual disconnection in Alzheimer's disease.

During a recent clinical and neuropathologic evaluation of a large population of brains collected at autopsy, attention was drawn to a subset of Alzheimer's disease (AD) patients presenting with prominent visual symptomatology as the first sign of the disease. In this population, a shift in the distribution of pathologic profiles had occurred such that the primary visual areas and the visual association areas had an increased number of lesions, whereas the prefrontal cortex had fewer lesions than usually observed in AD. Previous quantitative analyses have shown that generally in AD, primary sensory cortical areas are less damaged than association areas of the frontal and temporal lobes, as demonstrated by the laminar and regional distribution of two neuropathologic hallmarks of the disease, neurofibrillary tangles and neuritic plaques. Furthermore, the distribution of pathologic lesions in the AD cases with visual symptomatology revealed the disruption of specific visual association pathways, which are normally affected to a lesser degree in AD. These data suggest that in some cases of AD, the particular psychologic and neurologic symptomatology may be caused by the selective loss of specific corticocortical systems, as reflected by a differential distribution of the neuropathologic markers of the disease.

Alzheimer Disease↗

PubMed1990

Distribution of parvalbumin immunoreactivity in the visual cortex of Old World monkeys and humans.

The macaque visual system has been frequently used as a model for understanding functional aspects of human vision. There are, however, few studies directly comparing biochemically defined neuronal populations in the visual cortex of the two species. In this study we compared the distribution and morphological features of the parvalbumin-immunoreactive neuronal subpopulation within humans and Old World monkeys (Macaca fascicularis and Macaca mulatta) by using monoclonal antibodies against the Ca2(+)-binding protein parvalbumin (PV), a neuronal marker in the vertebrate cerebral cortex. Characteristic laminar density and distribution of PV is observed, matching that seen with cytochrome C-oxidase and gamma-aminobutyric acid (GABA) immunoreactivity. Thus, parvalbumin is prominent in the layers receiving afferents from the dorsal lateral geniculate nucleus. Terminal fields are rich in layer IVA and IVC and moderate in the blob-region of layer II-III of the monkey cortex. In the human visual cortex only layer IVC displays rich terminal fields. Parvalbumin is present in neurons within all layers of the cortex except layer I. Parvalbumin-immunoreactive (PV-ir) axons occur in different lamellae of the white matter containing axons belonging to association or projection neurons. The estimation of PV-ir neurons, determined for 50 microns-wide columns through the thickness of area 17, shows that the percentage of the total neuron number in area 17 of humans containing PV is 6.8 +/- 2.0%, and in the macaque monkey, 11.5 +/- 2.9%. The perikaryal area of PV-ir neurons varies according to the layer and is comparable in humans (109.3 +/- 40.8 microns2) and monkeys (94.3 +/- 29.5 microns2). However, the relative number of large PV-ir neurons is higher in humans. The immunoreactive product fills the thinnest cell processes and the shape of PV-ir neurons can be easily traced with the aid of a camera lucida. The shape of the neurons is similar in the two species studied, and they probably belong to non-spiny stellate, double-bouquet, chandelier, and basket cell classes. This study shows that parvalbumin acts as a marker for a subpopulation of interneurons in area 17, but it is also present in the geniculocortical as well as in corticocortical pathways. Moreover, the Old World monkey and human visual cortices have a similar, but not identical, distribution of this important calcium-binding protein.

Animals↗

PubMed1990

Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease: I. Superior frontal and inferior temporal cortex.

Various cytoskeletal proteins have been implicated in the cellular pathology of Alzheimer's disease. A monoclonal antibody (SMI32) that recognizes nonphosphorylated epitopes on the medium (168 kDa) and heavy (200 kDa) subunits of neurofilament proteins has been used to label and analyze a specific subpopulation of pyramidal neurons in the prefrontal and inferior temporal cortices of normal and Alzheimer's disease brains. In Alzheimer's disease, the distribution of neuropathological markers predominates in layers III and V in these association areas. In these neocortical regions, SMI32 primarily labels the perikarya and dendrites of large pyramidal neurons, predominantly located within layers III and V. In Alzheimer's disease, a dramatic loss of SMI32-immunoreactive (ir) cells was observed, affecting particularly the largest cells (i.e., cells with a cross-sectional perikaryal area larger than 350 microns 2). The staining intensity of the largest SMI32-ir neurons was significantly reduced in Alzheimer's disease cases, suggesting that an inappropriate phosphorylation of these cytoskeletal proteins may take place in the course of the pathological process. In addition, the SMI32-ir neuron loss and total neuron loss were highly correlated with neurofibrillary tangle counts, whereas such a correlation was not observed with neuritic plaque counts. These quantitative data suggest that SMI32-ir neurons represent a small subset of pyramidal cells that share certain anatomical and molecular characteristics and are highly vulnerable in Alzheimer's disease. Other studies have suggested that SMI32-ir neurons are likely to furnish long corticocortical projections. Thus, their loss would substantially diminish the effectiveness of the distributed processing capacity of the neocortex, resulting in a neocortical isolation syndrome as reflected by the clinical symptomatology observed in these patients. Such correlations between the expression of a selective cellular pathology and specific elements of cortical circuitry will increase our understanding of the molecular and cellular characteristics underlying a given neuronal subclass vulnerability in Alzheimer's disease or other neurodegenerative disorders.

Aged↗

PubMed1990

Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease: II. Primary and secondary visual cortex.

In this study we investigated the primary and secondary visual areas of normal and Alzheimer's disease brains by using the SMI32 antibody. It is known that in Alzheimer's disease primary sensory areas are usually less devastated than association cortices, although visual symptomatology has been documented early in the course of the disease. In area 17, the SMI32 antibody primarily labeled the perikarya and dentritic tree of the large Meynert cells and cells in layer IVB. Smaller neurons in layers III, V, and VI were also immunoreactive (ir). In area 18, very large SMI32-ir pyramidal neurons in layers III and V were observed. In both areas, staining intensity was correlated with cell size, the largest neurons being the most intensely stained. Only a few changes were observed in the Alzheimer's disease cases. The only statistically significant differences in SMI32-ir neuron counts between control and Alzheimer's disease brains occurred in layer IVB cells and Meynert cells in area 17, and in layer III cells in area 18. In contrast with association cortices, there were no changes in staining intensity in the visual areas. There were fewer neurofibrillary tangles and neuritic plaques in these areas than in prefrontal and inferior temporal cortex, and a correlation between neurofibrillary tangle counts and SMI32-ir neuron loss was only observed in layer III of area 18. These observations show that in the primary and secondary visual cortex, SMI32 also labeled a distinct subset of pyramidal cells that are known from data obtained in the monkey brain to furnish long corticocortical as well as subcortical projections. Interestingly, although there is much less cell and/or neurofibrillary tangle formation in these occipital regions than in prefrontal and temporal association areas, there is significant loss within key subsets of pyramidal cells. The selective loss of this particular subpopulation of pyramidal neurons will disrupt association pathways linking primary visual cortex with areas involved in higher level visual processing. The partial disconnection of such pathways may be relevant to the visual symptomatology frequently observed in Alzheimer's disease patients. These data further support the hypothesis that subtypes of pyramidal neurons with specific anatomical and molecular profiles may display a differential vulnerability in Alzheimer's disease.

Aged↗

PubMed1990

Morphology of the cells within the inferior temporal gyrus that project to the prefrontal cortex in the macaque monkey.

The primate neocortex possesses an extraordinary degree of regional specialization. Virtually all cortical functions are dependent upon a complex system of reciprocal connections between related cortical regions that allow for distributed information processing. Although some aspects of the organization of these corticocortical projections are understood, little is known about the morphology and afferents to the cells of origin of long corticocortical projections in primates. We combined intracellular injection of Lucifer Yellow (LY) in fixed tissue with in vivo retrograde transport of fast blue to study the dendritic morphology of neurons within the inferior temporal gyrus (ITG) and the superior temporal sulcus (STS) that furnish corticocortical projections to the prefrontal cortex. The fast blue retrogradely labeled cells formed two clearly defined bands within the inferior temporal cortex: a supragranular band that corresponded to layer III, and an infragranular band that corresponded to layers V and VI. After Lucifer Yellow intracellular filling, these retrogradely labeled cells projecting to the prefrontal cortex were found to be morphologically very heterogeneous. Although all filled cells had spiny dendrites, they presented a wide range of cell body sizes and dendritic tree morphologies. In layer III, the majority of cells were typical pyramids of various sizes. In layers V-VI, numerous typical pyramidal cells were present. In addition, significant numbers of modified pyramidal forms were found, including vertical and horizontal fusiform cells, asymmetrical pyramids and multipolar cells. The entire dendritic arbor of individual subtypes in layers III, V, and VI was restricted to a few cortical layers, but as a group these cells had dendrites spanning the whole cortical depth. We suggest that corticocortically projecting cells are distinct from subcortically projecting cells and consist of a defined set of morphological and functional subgroups, each of which is driven by a distinct set of afferents and likely possesses different response properties.

Animals↗

PubMed1990

Somatostatin immunohistochemistry of hippocampal slices with lucifer yellow-stained pyramidal neurons responding to somatostatin.

We have combined electrophysiology and immunohistochemistry to study the somatostatin (SS) innervation of neurons in the rat hippocampal slice. After recording the intracellular response of a pyramidal CA1 neuron in vitro to SS, Lucifer Yellow was injected into the cell and the slice fixed and processed for immunohistochemical localization of SS in the vicinity of the recorded neuron. Most pyramidal neurons (70%) responded to SS with a hyperpolarization associated with marked slowing of spontaneous discharge and reduced input resistance. SS-containing elements either crossed, ran parallel or seemingly terminated on the Lucifer Yellow-filled SS-responsive cell. These occurrences of close proximity of apparent pre- and postsynaptic elements were observed in all layers of the CA1 region and may represent synaptic terminations of SS elements on a pyramidal neuron that are likely to elicit membrane hyperpolarizations.

Animals↗