Functional implications of the radial organization of VIP-containing neurons in the neocortex.
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Animals↗
Biomedical subjects
J H Morrison
Publications and source records attributed to J H Morrison.
A monoclonal antibody to non-phosphorylated neurofilament protein marks the vulnerable cortical neurons in Alzheimer's disease.
Various cytoskeletal proteins have been implicated in the formation of neurofibrillary tangles in Alzheimer's disease. A monoclonal antibody to non-phosphorylated neurofilament protein labels a distinct subset of pyramidal cells in the normal human cortex which have a distribution very similar to that of neurofibrillary tangles in brains from patients with Alzheimer's disease. In addition, regions and layers that normally contain a high density of such cells, in Alzheimer's disease, have large numbers of neurofibrillary tangles and few remaining immunoreactive cells.
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Distribution of choline acetyltransferase-, serotonin-, dopamine-beta-hydroxylase-, tyrosine hydroxylase-immunoreactive fibers in monkey primary auditory cortex.
Immunohistochemical methods were used to visualize choline acetyltransferase (ChAT)-, serotonin-, dopamine-beta-hydroxylase (DBH)-, and tyrosine hydroxylase (TH)-containing fibers in the primary auditory cortex of the cynomolgus monkey (Macaca fascicularis). Each antiserum revealed a subpopulation of axons with a distinct density and laminar distribution. ChAT-immunoreactive fibers were very dense in superficial layers, particularly in layers I, deep III, and IV, and very sparse in layers V and VI. No immunoreactive cell bodies were evident. Serotonin-immunoreactive fibers were very dense in all cortical layers but exhibited some subtle laminar differences in fiber size and orientation. The densities of DBH- and TH-immunoreactive fibers were substantially lower than the densities of both ChAT- and serotonin-immunoreactive fibers, particularly in layer IV. However, there were substantial differences between the distribution of TH-immunoreactive fibers and that of DBH-immunoreactive fibers. For example, the density of TH-immunoreactive fibers was substantially greater than that of DBH-immunoreactive fibers in layer I. In addition, TH-immunoreactive fibers differed from the other three systems in that TH-immunoreactive fibers exhibited a rostral to caudal gradient of decreasing density. This is the first characterization of the innervation of a specific cortical region by all four of these systems and the first detailed description of the cholinergic innervation of a primate neocortical region utilizing a specific anti-ChAT antiserum. These striking differences in density and laminar distribution suggest that the subcortical extrathalamic systems furnishing these axons differ significantly in their modulation of cortical auditory processing. These data extend observations of previous studies which revealed that the expansion and specialization of the primate neocortex is accompanied by a pronounced regional and laminar differentiation in the intracortical distribution of these highly divergent, extrathalamic afferents.
Adrenergic Fibers↗
Localization of amyloid beta protein messenger RNA in brains from patients with Alzheimer's disease.
The distribution of cells containing messenger RNA that encodes amyloid beta protein was determined in hippocampi and in various cortical regions from cynomolgus monkeys, normal humans, and patients with Alzheimer's disease by in situ hybridization. Both 35S-labeled RNA antisense and sense probes to amyloid beta protein messenger RNA were used to ensure specific hybridization. Messenger RNA for amyloid beta protein was expressed in a subset of neurons in the prefrontal cortex from monkeys, normal humans, and patients with Alzheimer's disease. This messenger RNA was also present in the neurons of all the hippocampal fields from monkeys, normal humans and, although to a lesser extent in cornu ammonis 1, patients with Alzheimer's disease. The distribution of amyloid beta protein messenger RNA was similar to that of the neurofibrillary tangles of Alzheimer's disease in some regions, but the messenger RNA was also expressed in other neurons that are not usually involved in the pathology of Alzheimer's disease.
Alzheimer Disease↗
Subtractive cloning of complementary DNAs and analysis of messenger RNAs with regional heterogeneous distributions in primate cortex.
Morphological heterogeneity of individual neurons in the mammalian brain must ultimately result from differences between cells in their profiles of gene expression. However, the degree to which neurons located in different regions of the brain express different sets of genes is not known. Using differential cDNA cloning procedures, including subtractive hybridization and differential colony screening, a quantitative analysis of RNAs with heterogeneous distributions in the telencephalon of the rat and Old World monkey has been performed. The results suggest that no species of RNA exist with a distribution specific to the hippocampus or neocortex of the rat with an abundance greater than 0.05%. Additionally, the results with an abundance of 0.05% or greater which is present in neocortex of the monkey but absent from the cerebellum suggest that only one species of mRNA exists. A Northern blot analysis of cDNA clones representing mRNAs present in the neocortex but absent from the cerebellum of the monkey is presented, establishing the effectiveness of subtractive hybridization between different regions of the brain for cDNA cloning. Also presented is in situ hybridization analysis of the cellular distributions in primate neocortex of two mRNAs. One of these RNAs, detected by clone 1B4 is present in cortical laminae V and VI, and exhibits a high degree of heterogeneity in the overall density of labelled cells.
Animals↗
An immunohistochemical study of pro-somatostatin-derived peptides in the human brain.
The distribution of pro-somatostatin-derived-peptide-positive profiles was examined by indirect immunohistofluorescence in nine post-mortem human brains (age 58-73 years). Three specific antisera were used for this study which recognize, respectively, somatostatin-28, somatostatin-28 (1-12) and somatostatin (1-14). Pro-somatostatin-derived-peptide-positive immunoreactive profiles were observed throughout the neuraxis. Cell bodies were found within archeo-, paleo- and neocortical areas, the subcortical white matter, in the nucleus accumbens, caudate nucleus and putamen, as well as in the hypothalamus, the reticular thalamic nucleus and the reticular formation of the brainstem. Fibers and terminals were seen in the same areas as well as in various thalamic nuclei, in the brainstem and spinal cord. Pro-somatostatin-derived-peptide-positive fibre tracts include the bed nucleus of the stria terminalis, the diagonal band of Broca, the stria medullaris, the inter-thalamic adhesion, the posterior commissure and the spinothalamic tract. Furthermore, differences between human and animal brains were noted and some somatostatin systems reported which may be implicated in certain human neuropathological states.
Aged↗
Development of the noradrenergic, serotonergic, and dopaminergic innervation of neocortex.
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Afferent Pathways↗
Extrathalamic modulation of cortical function.
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Afferent Pathways↗
Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices.
The number of Thioflavine S-positive neurofibrillary tangles (NFT) and neuritic plaques (NP) was determined in visual and auditory cortical regions of 8 patients with Alzheimer's disease. On both a regional and laminar basis, NFT exhibited very distinctive and consistent distribution patterns. The mean (+/- SEM) number of NFT in a 250-micron-wide cortical traverse was very low in area 17, primary visual cortex (0.9 +/- 1.0), increased 20-fold in the immediately adjacent visual association cortex of area 18 (19.7 +/- 3.6), and showed a further doubling in area 20, the higher-order visual association cortex of the inferior temporal gyrus (35.5 +/- 8.8). Similar differences in NFT number were present between primary auditory (1.6 +/- 0.5) and auditory association (18.9 +/- 5.4) regions. On a laminar basis, NFT were predominantly present in layers III and V, although there were striking regional differences in the proportion of NFT in these 2 layers. Layer III contained 79% of the NFT in layers III and V in area 18, 41% in area 20, and only 27% in area 22. In contrast, NP showed different, and less specific, regional and laminar distribution patterns. Total NP number was similar in the 3 visual areas, although there were marked regional differences in the type of NP present. Nearly 80% of the NP in area 17 was of the NPc type (i.e., contained a dense, brightly fluorescent core), whereas over 70% of the NP in both areas 18 and 21 was of the NPnc type (i.e., lacked a dense, brightly fluorescent core). NP were present in every cortical layer but were most numerous in layers III and IV. The distinctive distribution patterns of NFT are very similar to the regional and laminar locations of long corticocortical projection neurons in homologous regions of monkey neocortex. This association suggests that NFT reside in the cell bodies of a subpopulation of pyramidal neurons, namely, those that furnish long corticocortical projections. In contrast, the distribution patterns of NP suggest that multiple neuronal systems contribute to their formation.
Aged↗
The distribution of tyrosine hydroxylase-immunoreactive fibers in primate neocortex is widespread but regionally specific.
An antiserum directed against tyrosine hydroxylase (TH), an enzyme involved in dopamine and norepinephrine synthesis, was used to visualize axons immunohistochemically in monkey neocortex. Labeled fibers were distributed throughout the entire neocortex, but they had striking patterns of regional and laminar specialization. For example, primary motor cortex contained the greatest density of TH-labeled fibers, whereas primary sensory regions were sparsely innervated. Marked heterogeneity of fiber density was also present among the association regions of the frontal, parietal, and temporal lobes. In addition, the laminar pattern of innervation in a given region was correlated with its fiber density. Sparsely innervated regions had labeled fibers only in layer I and sometimes layer VI. In regions of intermediate density, labeled fibers tended to be located in layers I-superficial III and layers V-VI, whereas in densely innervated motor cortex TH-immunoreactive fibers were present in all cortical layers. Comparison of these distribution patterns with those produced by an antiserum directed against dopamine-beta-hydroxylase (DBH), a specific marker of neocortical noradrenergic axons, revealed marked differences. DBH-immunoreactive fibers were observed in some cortical locations where few or no TH-labeled fibers were present. In other regions, the density of TH-immunoreactive processes far exceeded that of DBH-labeled fibers. These findings indicate that nearly all of the immunoreactive fibers revealed by this anti-TH antiserum are dopaminergic. This interpretation was further supported by lesions of the ascending noradrenergic fibers in the brain stem, which reduced DBH immunoreactivity, but not TH immunoreactivity, in neocortex. The distinctive innervation patterns of TH-immunoreactive fibers suggest a functional specialization of the dopaminergic projections to primate neocortex.
Animals↗
Regional heterogeneity in the distribution of somatostatin-28- and somatostatin-28(1-12)-immunoreactive profiles in monkey neocortex.
The distribution of the prosomatostatin-derived peptides (PSDP), somatostatin-28 and somatostatin-28(1-12), in the cynomolgus monkey (Macaca fascicularis) neocortex was characterized in quantitative immunohistochemical studies of 3 visual areas (V1, primary visual cortex; V2, the adjacent visual association area; and AIT, a visual association area in anterior inferior temporal cortex), 2 auditory areas (AI, primary auditory cortex; and T1, an adjacent auditory association area) and anterior cingulate cortex (Area 24). The results of similar quantitative analyses in 3 homologous areas in rat neocortex (primary visual, primary auditory, and anterior cingulate) are also presented. Primate cortical areas differed significantly in both density and laminar distribution of PSDP-immunoreactive profiles. Area 24, the most densely labeled area, had nearly 6 times as many PSDP-immunoreactive neurons as V1. Both auditory areas contained approximately two-thirds the number of PSDP-immunoreactive neurons found in Area 24; however, both had nearly 4 times as many immunoreactive neurons as V1. The 3 visual areas showed incremental increases in the number of PSDP-immunoreactive neurons; V2 contained nearly twice and AIT nearly 3 times the number of immunoreactive neurons present in V1. Both the supra- and infragranular layers were densely labeled in Area 24 and Area T1, however, in AI, V1, V2, and AIT the infragranular layers were relatively sparsely labeled. In contrast to the regional heterogeneity found in the primate neocortex, the distribution of immunoreactive neurons was quite uniform across the 3 rat cortical areas. The rat cortical areas contained substantially fewer immunoreactive neurons than most of the monkey cortical areas, and a majority of these immunoreactive neurons were located in the infragranular layers. These findings suggest that the regional specialization of primate neocortex involves the selective distribution of PSDP-immunoreactive neurons. They also suggest that chemically specified intrinsic organization of neocortex is not likely to be uniform across species or across cortical areas in the primate. The distinctive regional distribution patterns of PSDP-immunoreactive profiles appear to parallel that of the long corticocortical projections (contralateral and distant ipsilateral projections), suggesting an association between these presumed inhibitory interneurons and this important extrinsic system.
Animals↗
An immunohistochemical characterization of somatostatin-28 and somatostatin-281-12 in monkey prefrontal cortex.
The distribution of the prosomatostatin-derived peptides (PSDP) somatostatin-28 (SS-28) and somatostatin-281-12 (SS-281-12) was characterized immunohistochemically in the prefrontal cortical regions of both Old World cynomolgus monkeys (Macaca fascicularis) and New World squirrel monkeys (Saimiri sciureus). Comparison of staining with antisera specific for each peptide revealed that these antigens were segregated within immunoreactive neurons such that SS-28 was largely confined to the perinuclear region of the cell body whereas SS-281-12 was primarily found in axons and dendrites. The laminar pattern of immunoreactive fibers was similar in all areas of the prefrontal cortex. The most dense terminal arborization was in layers I, II, and superficial III. Deep III and IV were traversed by radial fibers that had little arborization. Layers V and VI contained both radial fibers and a moderately dense terminal plexus. Labeled fibers were less numerous in the white matter. There were marked regional differences in fiber density. Areas 12 and 24 had the greatest density of immunoreactive fibers, areas 9, 11, and 25 were of intermediate density, and areas 10 and 46 were the least dense. Most of the immunoreactive cells appeared to be multipolar or bitufted. They were found throughout all cortical layers and the white matter. The largest number were located in layers II, superficial III, and deep V and VI. There were also marked regional differences in cell body density, which paralleled the regional differences in fiber density. Area 24 (anterior cingulate) had the greatest density of immunoreactive cell bodies (148 +/- 14/mm2), area 9 was of intermediate density (109 +/- 13/mm2), and area 46 was the least dense (83 +/- 12/mm2). Our findings indicate that PSDP compose a complex and extensive cortical system that is largely or totally intrinsic. The substantial regional heterogeneity in density exhibited by PSDP-containing neurons has not previously been reported for an intrinsic cortical system. The laminar and regional innervation patterns of these fibers and cell bodies suggest that the PSDP cortical system may play an important role in the polymodal information processing that occurs in association regions of prefrontal cortex.
Animals↗
Noradrenergic and serotoninergic innervation of cortical, thalamic, and tectal visual structures in Old and New World monkeys.
Antisera directed against human dopamine-beta-hydroxylase and against serotonin were used to characterize the noradrenergic (NA) and serotoninergic (5-HT) innervation of several cortical and subcortical visual areas in squirrel monkey (Saimiri sciureus) and cynomolgus monkey (Macaca fascicularis). Few species differences were observed for either monoamine. Cortical areas 17 and 18, as well as visual areas in the temporal and parietal lobe were found to exhibit regional specialization of both 5-HT and NA innervation. Precisely at the border between areas 17 and 18, the laminar innervation patterns and density characteristic of NA fibers in area 17 (Morrison et al., '82a; Kosofsky et al., '84) shift so that layer IV of area 18 contains more fibers than layer IV of area 17, and the overall density of fibers in area 18 is higher. For 5-HT, the highly laminated patterns characteristic of area 17 (Morrison et al., '82a; Kosofsky et al., '84) also observe this cytoarchitectonic boundary. Fibers in area 18 are more evenly distributed across laminae, and the overall density of fibers decreases. The visual region of the inferotemporal cortex was found to be very lightly innervated by NA fibers and very densely innervated by 5-HT fibers. Area 7 of the parietal lobule was more densely innervated by NA fibers, and less densely innervated by 5-HT fibers, than any other visual cortical region examined. The visual thalamic nuclei exhibited even greater regional differences in the density of NA innervation. The lateral geniculate nucleus was found to be virtually devoid of NA fibers, while the pulvinar-lateral posterior complex was densely innervated. The density of 5-HT fibers was more uniform across thalamic visual nuclei. The lateral geniculate, pulvinar, and lateral posterior nuclei all exhibit a moderate to high density of immunoreactive fibers. In the mesencephalon, the superficial layers of the superior colliculus were found to be densely innervated by NA fibers, whereas 5-HT fibers were most dense in the intermediate layers. These patterns of innervation indicate that, in these primate species, functionally related visual regions share common and distinguishable densities of NA innervation. Specifically, tecto-pulvinar-juxtastriate structures are more densely innervated than geniculo-striate and inferotemporal structures. These relationships suggest that, within the visual system, NA fibers preferentially innervate the regions involved in spatial analysis and visuomotor response rather than those involved in feature extraction and pattern analysis.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
An immunohistochemical study of six biologically active peptides in the human brain.
The morphological characteristics and distribution patterns of neurons immunoreactive for antisera against six biologically active peptides were examined by indirect immunofluorescence in the human brain. The peptides studied were: met-enkephalin, leu-enkephalin, substance P, somatostatin, cholecystokinin and vasoactive intestinal peptide. The tissue samples for this study were removed, dissected and placed into fixative within 4 h post-mortem. Regional differences throughout the entire neuraxis were observed in the localization of cell bodies, fibers and terminals for the various peptides. The observations reported in this article demonstrate certain distribution patterns for peptide immunoreactivities that appear to be specific to the human brain when compared to other species. These morphologic studies establish a valuable framework for the further analysis of the role of peptide-containing neuronal circuits in normal and diseased human brain.
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An experimental analysis of the origins of somatostatin-like immunoreactivity in the dentate gyrus of the rat.
In previous studies, fibers demonstrating somatostatin-like immunoreactivity were observed in the outer half of the molecular layer of the dentate gyrus in the rat and monkey. They occupy the same region as those of the perforant pathway that originates in the entorhinal cortex. Numerous somatostatin immunoreactive neuronal cell bodies were also observed in the hilar region, though stained axonal profiles could not be followed from these cells into the molecular layer. In the present study, several experimental procedures were employed to determine the origin of the somatostatin-positive fibers in the molecular layer. Transection of the perforant path fibers resulted in such characteristic changes as shrinkage of the molecular layer and sprouting of AChE-positive fibers. There was no apparent decrease, however, in the density of somatostatin-positive fibers. In fact, since the stained fibers occupied a narrower band in the shrunken molecular layer, their density appeared greater. Injections of kainic acid into the hilar region produced a lesion of hilar neurons, including those positive for somatostatin. In the region of cell loss, there was a marked reduction of somatostatin-immunoreactive fibers in the ipsilateral molecular layer, with no detectable changes in the homotopic contralateral molecular layer. The distribution of AChE fibers, which presumably have an extrinsic origin, was not altered by the treatment. In a final series of experiments, the retrograde tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into the hilar region and sections were prepared for the simultaneous demonstration of the tracer and of somatostatin-like immunoreactivity. Somatostatin-positive neurons demonstrating WGA-HRP reaction product were observed primarily in the ipsilateral hilar region, but a few double-labeled cells were also seen in the same area of the contralateral side. These studies indicate that a population of intrinsic neurons located in the polymorphic layer of the dentate gyrus projects to the outer half of the ipsilateral molecular layer. A similar, but very much smaller, projection also extends to the contralateral dentate gyrus. Taken together, these projections appear to account for much of the somatostatin-like immunoreactivity in the molecular layer of the dentate gyrus.
Animals↗
The monoaminergic innervation of primate neocortex.
In brain, the monoamines, dopamine, norepinephrine, and serotonin, are confined to anatomically distinct neuronal systems, each of which furnishes widespread projections to neocortex. In primate, but not in rat, the terminal patterns of each of these systems have a high degree of regional and laminar specificity. These findings suggest that there are different sites of action and possibly different functional roles for each of the monoamines. This type of precise anatomic information is essential to our understanding of the possible involvement of monoamines in human disease states.
Animals↗
The distribution of somatostatin-like immunoreactivity in the monkey hippocampal formation.
The distribution of somatostatin-like immunoreactivity was studied in the hippocampal formation of the Old World (Macaca fascicularis) and New World (Saimiri sciureus) monkeys. Series of coronal sections were processed by the unlabeled second antiserum method using primary antisera which recognize somatostatin-28 (S309) or somatostatin-28(1-12) (S320). Neuronal cell bodies were more readily stained with antiserum S309 and were observed throughout the hippocampal formation. The most prominent accumulations of stained neurons occur in the hilar region of the dentate gyrus, in strata oriens and pyramidale of regio inferior of the hippocampus, and in the deep layers of the entorhinal cortex. Both antisera demonstrated extensive fiber systems which varied in density regionally in the hippocampal formation. Stained fibers were most prominent in the outer two-thirds of the molecular layer of the dentate gyrus, in stratum lacunosum-moleculare of the hippocampus, in layer I of the presubiculum and in layers I, III, and V of the entorhinal cortex.
Animals↗
Somatostatin-28 [1-12]-like peptides.
The search for a peptide corresponding to the NH2-terminus of somatostatin-28 (SS-28) in tissues has led to the isolation and characterization of somatostatin-28[1-12] from pancreas and hypothalamus. Somatostatin-28[1-12]-like immunoreactivity [SS-28 [1-12]-LI] is widely distributed throughout the central nervous system and the digestive system of rodents and primates, reaching levels comparable to those of somatostatin-14 (SS-14). Antibodies directed against the C-terminal end of the dodecapeptide are more specific and constitute excellent markers for the "prosomatostatin" system in mammalian tissues. In rat brain, SS-28[1-12]-LI material is highly concentrated in nerve fibres and terminals, especially in the median eminence, layer I of neocortex, the outer molecular layer of the dentate gyrus and the striatum. Additionally, immunoreactivity is observed in large multipolar or occasionally pyramidal-like neurons of the neocortex. SS-28[1-12] is secreted from hypothalamus and amygdala by a calcium dependent mechanism. No biological role is presently known for the dodecapeptide. Two other peptides of Mr = 8000 (8 K) and Mr = 5000 (5 K) which contain SS-28[1-12] at their carboxy-termini are present in acid extracts from rat pancreas, brain and spinal cord. These two peptides were isolated from an acid extract of rat brains using ion-exchange chromatography, gel permeation chromatography and reverse-phase HPLC. Results from amino acid analysis and partial sequencing were compared to the sequence of the cDNA encoding rat pre-prosomatostatin (prepro-SS) and revealed that the 8 K peptide is a 76 amino acid molecule corresponding to prepro-SS[25-100] and that the 5K peptide, which contains 44 amino acids, corresponds to prepro-SS [57-100]. The 5 K peptide was generated after cleavage of a Leu-Leu bond at position 56-57 of prepro-SS. The four most predominant peptides of the "prosomatostatin system" presently characterized are: SS-14, SS-28[1-12], SS-28 and prepro-SS[25-100]. Studies on pooled perfusates from rat hypothalamic tissue show that prepro-SS[25-100] is released with SS-28[1-12] in vitro and accounts for 22% of the total SS-28[1-12]-like immunoreactive material released during depolarization. The 5 K peptide is apparently not secreted. The presence of prepro-SS[25-100] in brain implies that, first, prosomatostatin can serve as an immediate precursor for SS-14 without going through SS-28 as an intermediate step and second, other peptides could conceivably be derived from the cryptic portion of the precursor.
Amygdala↗