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PubMed2000

Spinal cord glioneuronal tumor with "rosetted" neuropil islands and meningeal dissemination: a case report.

Distinctive glioneuronal tumors arising within the cerebrum and displaying neuropil-like islands and tumor cells immunoreactive for neuronal and glial antigens have recently been described. We report a similar tumor in the cervico-thoracic region of the spinal cord in a 44-year-old woman that recurred 1 year later with dissemination to the lumbar dura and cauda equina. The tumor was composed of "rosetted" neuropil islands displaying immunoreactivity for synaptophysin, whereas the intervening tumor cells were more fibrillar and immunoreactive for GFAP. The tumor cell nuclei immediately surrounding these neuropil islands were immunoreactive to the newly characterized neuronal marker, anti-Hu. While several cases of neurocytomas have been described in the spinal cord, to the best of our knowledge, this is the first example of a glioneuronal tumor with "rosetted" neuropil islands to be reported in the spinal cord.

Adult↗
PubMed2005

Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates.

We report seven patients, six from a single institution, who developed subacute limbic encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [(18)F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50% of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal teratoma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigens concentrated in areas of high dendritic density or synaptic-enriched regions of the hippocampus or cerebellum. Preliminary characterization of these antigens indicates that they are diverse and expressed on the neuronal cell membrane and dendrites; they do not co-localize with VGKCs, but partially co-localize with spinophilin. A target autoantigen in one of the patients co-localizes with a cell surface protein involved in hippocampal dendritic development. All patients except the one with antibodies to intracellular antigens had dramatic clinical and neuroimaging responses to immunotherapy or tumour resection; two patients had neurological relapse and improved with immunotherapy. Overall, the phenotype associated with the novel neuropil antibodies includes dominant behavioural and psychiatric symptoms and seizures that often interfere with the evaluation of cognition and memory, and brain MRI or FDG-PET abnormalities less frequently restricted to the medial temporal lobes than in patients with classical paraneoplastic or VGKC antibodies. When compared with patients with VGKC antibodies, patients with these novel antibodies are more likely to have CSF inflammatory abnormalities and systemic tumours (teratoma and thymoma), and they do not develop SIADH-like hyponatraemia. Although most autoantigens await characterization, all share intense expression by the neuropil of hippocampus, with patterns of immunolabelling characteristic enough to suggest the diagnosis of these disorders and predict response to treatment.

Adult↗
PubMed1999

Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice.

How aggregates of polyglutamine proteins are involved in the neurological symptoms of glutamine repeat diseases is unknown. We show that huntingtin aggregates are present in the neuronal processes of transgenic mice that express exon 1 of the Huntington's disease (HD) gene. Unlike aggregates in the nucleus, these neuropil aggregates are usually smaller and are not ubiquitinated. Electron microscopy reveals many neuropil aggregates in axons and axon terminals. Huntingtin aggregates in the axon terminal are co-localized with some synaptic vesicles, implying that they may affect synaptic transmission and neuronal communication. The formation of neuropil aggregates is highly correlated with the development of neurological symptoms. The present study raises the possibility that neuropil aggregates may cause a dysfunction in neuronal communication and con-tribute to the neurological symptoms of HD.

Animals↗
PubMed2004

Comparative morphology of central neuropils in the brain of arthropods and its evolutionary and functional implications.

Most insects and decapod crustaceans possess an assemblage of midline neuropils, the central complex. Recent phylogenetic studies show a sister-group relationship between hexapods and decapods, suggesting that central complexes in both groups are homologous structures derived from a basal ancestral neuropil. This ancestral archetype of the central complex (lacking the protocerebral bridge) might be represented in the chilopods. Until recently, diplopods were regarded as closely related to chilopods and united within the taxon "Myriapoda". The entire lack of a midline neuropil in diplopods, however, renders the monophyletic origin of the class Myriapoda unlikely. In this study we used a palette of immunocytochemical and neuroanatomical methods to investigate mid-line neuropils in hitherto poorly examined arthropod groups. Of special interest for resolving arthropod phylogeny are onychophorans, who are believed to be an evolutionary ancient group that resembles the ancestors of modern arthropods. Striking similarities in central brain neuroarchitecture of the onychophoran Euperipatoides rowellii and of a chelicerate species, however, suggest a close phylogenetic relationship between these two groups. Our findings imply that onychophorans either represent the oldest form of the chelicerates or that extant onychophorans have developed from chelicerate-like ancestors by neoteny.

Animals↗
PubMed1999

Genetic analysis of the Drosophila ellipsoid body neuropil: organization and development of the central complex.

The central complex is an important center for higher-order brain function in insects. It is an intricate neuropil composed of four substructures. Each substructure contains repeated neuronal elements which are connected by processes such that topography is maintained. Although the neuronal architecture has been described in several insects and the behavioral role investigated in various experiments, the exact function of this neuropil has proven elusive. To describe the architecture of the central complex, we study 15 enhancer-trap lines that label various ellipsoid body neuron types. We find evidence for restriction of gene expression that is correlated with specific neuronal types: such correlations suggest functional classifications as well. We show that some enhancer-trap patterns reveal a single ellipsoid body neuron type, while others label multiple types. We describe the development of the ellipsoid body neuropil in wild-type animals and propose developmental mechanisms based on animals displaying structural mutations of this neuropil. The experiments performed here demonstrate the degree of resolution possible from the analysis of enhancer-trap lines and form a useful library of tools for future structure/function studies of the ellipsoid body.

Animal Structures↗
PubMed1996

Leech photoreceptors project their galectin-containing processes into the optic neuropils where they contact AP cells.

We characterized a subset of leech sensory afferents, the photoreceptors, in terms of their molecular composition, anatomical distribution, and candidate postsynaptic partners. For reagents, we used an antiserum generated against purified LL35, a 35 kD leech lactose-binding protein (galectin); monoclonal antibody (mAb) Lan3-2, which is specific for a mannose-containing epitope common to the full set of sensory afferents; and dye injections. Photoreceptors differ from other types of sensory afferents by their abundant expression of galectin. However, photoreceptors share in common with other sensory modalities the mannose-containing epitope recognized by mAb Lan3-2. Photoreceptors from a given segment project their axons directly into the CNS ganglion innervating the same segment. They assemble in a target region, the optic neuropil, which is separate from the target regions of other sensory modalities. They also extend their axons as an optic tract into the connective to innervate optic neuropils of other CNS ganglia, thereby providing extensive intersegmental innervation for the 33 CNS ganglia comprising the leech nerve cord. Because of its intimate contact with the optic neuropil, a central neuron, the AP effector cell, is a strong candidate second order visual neuron. In confocal images, the AP cell projects its primary axon for about 100 microns alongside the optic neuropil. In electron micrographs, spines emanating from the axon of the AP cell make contact with vesicle laden nerve terminals of photoreceptors. Leech photoreceptors and their second order visual neurons represent a simple visual system for studying the mechanisms of axonal targeting.

Animals↗
PubMed1997

Genetic influences on cellular reactions to CNS injury: the reactive response of astrocytes in denervated neuropil regions in mice carrying a mutation (Wld(S)) that causes delayed Wallerian degeneration.

This study compares the reactive changes in astrocytes in denervated neuropil regions in normal mice and in mice carrying the Wld(S) mutation which leads to delayed Wallerian degeneration. In situ hybridization and immunocytochemical techniques were used to define the time course of changes in the levels of glial fibrillary acidic protein (GFAP) and GFAP mRNA in the denervated neuropil of the hippocampus after unilateral aspiration lesions of the entorhinal cortex. In control mice, GFAP mRNA levels increased rapidly in the denervated neuropil to a peak that was about tenfold higher than control at 2-4 days, decreased between 6 and 8 days postlesion, and then increased again to a second peak at 10 days postlesion. Increases in immunostaining for GFAP were evident by 2 days, remained elevated until 12 days postlesion and then decreased slowly. In mice carrying the Wld(S) mutation, the upregulation of GFAP mRNA levels in the denervated laminae was substantially delayed. Strikingly absent was the dramatic increase in labeling at 2-4 days postlesion which was such a prominent feature of the response in control animals. Peak labeling in the denervated laminae was not seen until 10-12 days postlesion. The development of a well-defined band of intensely immunostained and hypertrophied astrocytes in the denervated zone was also delayed in the Wld(S) animals, although there were modest increases in immunostaining as early as 2 days postlesion that were seen throughout the hippocampus ipsilateral to the lesion. These results suggest that degenerative changes in axons and synaptic terminals are the principal trigger for upregulating GFAP expression in the denervated neuropil, although other signals also play a role in the early postlesion response.

Animals↗
PubMed1978

Regional variations in glia and neuropil within the hypothalamic ventromedial nucleus.

The normal fine structure of glia and neuropil in the various regional subdivisions of the hypothalamic ventromedial nucleus in the adult male albino rat is described in this report. Although most HVM astrocytes throughout the nucleus appear ordinary in cytology, certain astrocytes found in the posterior ventrolateral subdivision of the nucleus appear somewhat reactive, in that they contain numerous thick fascicles of gliofibrils and pleomorphic dense bodies. The processes of these reactive astrocytes elaborate multiple, concentric lamellae which encapsulate small, round, pyknotic masses (probably degenerate axonal elements). These degenerate profiles, which are greatly outnumbered by normal HVM boutons, may represent synaptic contacts that deteriorate spontaneously in the normal adult HVM. Other signs of spontaneous degeneration occurring within this neuropil include the occasional presence of large masses of necrotic debris which appear engulfed by microglia. These findings suggest the presence in the normal adult HVM neuropil of a low-grade degenerative process with attendant gliosis, which is topographically centered about the posterior ventrolateral region of the nucleus. Regions of neuropil containing degenerate boutons also contain altered neuronal processes, some of which may be growth cones. The topographic proximity of the degenerating boutons to possible signs of axonal or dendritic regeneration indicates that certain synaptic circuits in the normal adult HVM may be plastic, and subject to spontaneous remodelling.

Animals↗
PubMed1990

Histaminelike immunoreactive neurons innervating putative neurohaemal areas and central neuropil in the thoraco-abdominal ganglia of the flies Drosophila and Calliphora.

The fused thoraco-abdominal ganglia of the flies Calliphora vomitoria and Drosophila melanogaster were investigated immunocytochemically with antisera against histamine. In both insect species, 18 histaminelike immunoreactive (HA-IR) neurons were resolved in these ganglia. Six of these neurons have cell bodies in the thoracic neuromeres and 12 in the fused abdominal neuromeres. All cell bodies are situated ventrally. In Calliphora all cell bodies are arranged in a segmental pattern. In Drosophila only the thoracic cell bodies have a segmental arrangement, whereas the abdominal ones are clustered anteriorly close to the last thoracic neuromere. In both species the six thoracic neurons supply processes to the synaptic neuropil in the thoracic neuromeres and to the dorsal neural sheath. The processes in the neural sheath run anteriorly in the lateral portions of the ganglion into the cervical connective. In a few regions laterally arborizing terminals are found in putative neurohaemal areas. These areas were investigated by electron microscopic immunocytochemistry in Calliphora. The HA-IR terminals (containing small granular vesicles) were found outside the "blood-brain barrier" below the acellular basal lamina of the neural sheath. Release of histamine into the circulation is therefore theoretically possible. The central processes of the six thoracic HA-IR neurons may interact synaptically with large numbers of other neurons in the neuropil, and the peripheral varicose fibers from the same HA-IR neurons possibly are neurohaemal release sites. The abdominal HA-IR neurons, in contrast, form extensive arborizations within the synaptic neuropil only. Both thoracic and abdominal neurons have ipsilateral and contralateral branches as well as processes that invade more than one neuromere. A single HA-IR neuron thus invades large volumes of synaptic neuropil. Histamine may be used by neurons of the ventral ganglia both as neurotransmitter (or neuromodulator) and as a circulating neurohormone released from the neural sheath.

Animals↗
PubMed1993

Two visual systems in one brain: neuropils serving the secondary eyes of the spider Cupiennius salei.

Like other araneans, the wandering spider Cupiennius salei is equipped with one pair of principal eyes and three pairs of secondary eyes. Primary and secondary eyes serve two distinct sets of visual neuropils in the brain. This paper describes cellular organization in neuropils supplied by the secondary eyes, which individually send axons into three laminas resembling their namesakes serving insect superposition eyes. Secondary eye photoreceptors send axons to small-field projection neurons (L-cells) which extend from each lamina to supply three separate medullas. Each medulla is a vault of neuropil comprising only a few morphological types of neurons. These can be compared to a subset of retinotopic neurons in the medullas of calliphorid Diptera supplying giant motion-sensitive neurons in the lobula plate. In Cupiennius, neurons from secondary eye medullas converge at a single target neuropil called the "mushroom body." This region contains giant output neurons which, like their counterparts in the calliphorid lobula plate, lead to descending pathways that supply thoracic motor circuits. It is suggested that the cellular arrangements serving Cupiennius's secondary eyes are color independent pathways specialized for detecting horizontal motion. The present results do not support the classical view that the spider "mushroom body" is phylogenetically homologous or functionally analogous to its namesake in insects.

Animals↗
PubMed1995

Ca2+ influx into leech neuropile glial cells mediated by nicotinic acetylcholine receptors.

The effect of cholinergic agonists and antagonists on the intracellular free Ca2+ concentration ([Ca2+]i) of leech neuropile glial cells was investigated by use of iontophoretically injected fura-2. In neuropile glial cells, cholinergic agonists induced a marked increase in [Ca2+]i that was inhibited by d-tubocurarine, alpha-bungarotoxin, strychnine, and atropine. The efficacy of the various agonists and antagonists indicates that the [Ca2+]i increase is mediated by the nicotinic acetylcholine (ACh) receptors that have been characterized previously in these cells by using electrophysiological methods. In the presence of high agonist concentrations, [Ca2+]i partly recovered, suggesting that the ACh receptors desensitize. The [Ca2+]i increase induced by cholinergic agonists was abolished in Ca2(+)-free solution, which indicates that it is caused by Ca2+ influx from the external medium. The agonist-induced [Ca2+]i increase was partly preserved in Na(+)-free solution, whereas the agonist-induced membrane depolarization was strongly suppressed. The agonist-induced [Ca2+]i increase was also partly preserved in the presence of 5 mM Ni2+, which almost abolished the K(+)-induced [Ca2+]i increase mediated by voltage-dependent Ca2+ channels. It is concluded that at low agonist concentrations the [Ca2+]i increase in leech neuropile glial cells is mediated exclusively by the ion channels associated with the nicotinic ACh receptors. At high agonist concentrations, voltage-dependent [Ca2+]i increase in leech neuropile glial cells is mediated exclusively by the ion channels associated with the nicotinic ACh receptors. At high agonist concentrations, voltage-dependent Ca2+ channels activated by the concomitant membrane depolarization also contribute to the agonist-induced Ca2+ influx.

Animals↗
PubMed1976

Organization of crustacean neuropil. II. Distribution of synaptic contacts on identified motor neurons in lobster stomatogastric ganglion.

Identified neurons in the stomatogastric ganglion of the lobster were examined and reconstructed by serial section electron microscopy. Each motor neuron consists of a soma, a primary process leading directly from the soma to the motor axon which leaves the ganglion, and a group of secondary processes which branch from the primary process and ramify within the neuropil. Synapses are found only on small processes in the synaptic neuropil, never on the primary processes or on larger secondary processes in the coarse neuropil. Nearly every secondary process of every neuron examined makes both pre- and postsynaptic contacts. Hence these neurons are not polarized into distinct pre- and postsynaptic regions but have both input and output distributed over each of the secondary processes in the neuropil. The conncetion between a specific pair of neurons is also distributed over several branches of both the pre- and the postsynaptic neurons. The restriction of synapses to the more distal portions of the secondary processes suggests that no single contact or localized group of contacts can exert an overrriding influence on the neuron by virtue of an especially advantageous position. The close proximity of input and output on most secondary processes suggests that synaptic input may be capable of directly influencing output without the intervention of action potentials. The distribution of specific synapses over several branches of both pre- and postsynaptic neurons suggests that each neuron functions as a whole without differentiation into specialized branches.

Animals↗
PubMed1985

Varicosity-associated antigens define neuropile subfields in the leech central nervous system.

A panel of twelve monoclonal antibodies raised against homogenates of leech nerve cords and four polyclonal antisera raised against purified neurotransmitters were used to label varicosities immunocytologically in the central neuropile of leech segmental ganglia. These immunoreactive varicosities occur in distinct patterns, some of which have a simple geometry. Three antibodies label immunoreactive varicosities distributed in a single dorsoventrally-oriented plane, two label varicosities distributed in lateral hemi-neuropiles (leaving void a central cephalocaudal passageway), and five label varicosities distributed throughout the neuropile. Six antibodies tested label varicosities across leech species, and five of these varicosity populations are distributed in patterns conserved across leech species. Immunocytologically-defined neuropile subfields do not correspond with previously identified histological and ultrastructural features of leech segmental ganglia. Analysis of immunocytologically-defined subfields is extended to include identification of sets of neurons which appear to project into these subfields, and to include an intracellular characterization of one of these neuron sets.

Animals↗
PubMed1980

Membrane specializations in the first optic neuropil of the housefly, Musca domestica L. I. Junctions between neurons.

Thin section and freeze-fracture replicas of the first optic neuropil (lamina ganglionaris) of the fly Musca were studied to determine the types, extent and location of membrane specializations between neurons. Five junctional types are found, exclusive of chemical synapses. These are gap, tight and septate junctions, close appositions between retinular (R) axons and capitate projections (in which an epithelial glial cell invaginates into an R axon). Junctional types and their cellular associations follow: gap junctions, between lamina (L) interneurons, L1-L2; tight junctions, between L1-L2; L3-L4; L4-epithelial glial cell; and R7-R8. Septate junctions, between L1-L2, L3-L4, L3-beta, L4-beta, alpha-beta, and an unidentified fibre making septate junctions with L1 and L2. Close appositions are found between R axons in the distal portion of the optic cartridges of this neuropil prior to extensive R chemical synapses with L1, L2. These loci (seen in freeze-fracture replicas) have rhomboidal patches of hexagonally arrayed P face particles. Intermembranous clefts between R axons are about 50 A and are invariably electron lucent. These points of near contact between R terminals are probably the sites of low electrical resistance measured by Shaw (1979). Capitate projections are for the first time revealed in freeze fracture surfaces. Here epithelial glia send many, short, mushroom-shaped processes invaginating into R axons forming a tenacious structural bond. All four membrane leaflets (P and E faces of R axon and glial membrane) in the capitate projection possess particles in higher densities than in the surrounding nonspecialized regions. The known, general functions of each membrane specialization were correlated with the functional capacities of those lamina neurons possessing them in an effort to interpret better the integrative capacity of this neuropil. These data provide some fine structural bases for a putative 'blood-brain' barrier between lamina and haemolymph, between lamina and peripheral retina, and possibly between lamina and second optic neuropil.

Animals↗
PubMed1981

The fine structure of the submucous plexus of the guinea-pig ileum. I. The ganglia, neurons, Schwann cells and neuropil.

A fine structural study was made of the ganglia, neurons, Schwann cells and neuropil of the submucous plexus of the guinea-pig ileum. The arrangement of the plexus as seen by light microscopy is briefly described. Submucous ganglia are small, containing an average of eight neurons per ganglion (compared with 43 in myenteric ganglia) and are connected with each other by fine nerve strands. The cell bodies of neurons and Schwann cells and a neuropil consisting of neuronal and Schwann cell processes from the ganglia. No other cell types or blood vessels are found within the ganglia. Ganglia are surrounded by a continuous basal lamina but lack a well-defined connective tissue investment. The glial investment of neurons is incomplete: many neurons lie directly beneath the basal lamina with no intervening Schwann cell processes, and the plasma membranes of adjacent neurons are often directly apposed over large areas. Other areas of apposition occur between the cell bodies and processes of neurons and Schwann cells. Desmosome-like membrane specializations may be seen between neurons and other neurons or Schwann cells. Submucous neurons could not be categorized according to size, shape, organelle content or types of processes. Processes emerging from nerve-cell bodies were placed into four broad categories on the basis of shape and microtubule content. Many bundles of closely apposed small nerve profiles lacking intervening Schwann processes are found in the neuropil in addition to a large number of vesiculated varicosities, some of which are directly apposed to the plasma membranes of nerve-cell bodies. A small proportion of vesiculated profiles from synapses with nerve cell bodies, their processes and profiles in the neuropil. From their structure, submucous neurons appear to form a more homogeneous population than myenteric neurons. Because of their incomplete investment they are more likely to be freely exposed to substances diffusing in the extraganglionic tissue than are neurons of sympathetic ganglia.

Animals↗
PubMed1976

Relative cerebral glucose uptake of neuronal perikarya and neuropil determined with 2-deoxyglucose in resting and swimming rat.

An autoradiographic method using tracer amounts of [14C]-2-deoxy-D-glucose (2-DG) was used to detect areas of the brain in which glucose consumption was altered in swimming as compared to resting rats. Areas in which changes occurred in the swimming rat were widespread in gray matter, being greatest in the cerebellar vermis and least in portions of the cerebellar hemispheres and the inferior colliculi. Improved resolution was obtained with an autoradiographic method for [3H]-2-DG. The number of grains per unit area over neuronal perikarya was either slightly greater or equal to that over the immediately surrounding neuropil in both resting and swimming rats. This indicated that the glucose consumption of neuronal perikarya and the immediately surrounding neuropil per unit volume were similar. Since gray matter is composed predominantly of neuropil, the present results indicate that the bulk of the total brain gray matter glucose consumption is accounted for by neuropil in both the resting and swimming states.

Animals↗
PubMed1988

Transplanted astrocytes reduce synaptic density in the neuropil of cerebellar cultures.

Cytosine arabinoside-treated neonatal mouse cerebellar cultures, devoid of granule cells and mature glia, demonstrate heterologous synapses between sprouted Purkinje cell recurrent axon collaterals and dendritic spines in the neuropil. Such cultures were transplanted with optic nerve as a source of glia, and the effect on neuropil synapses was investigated. There was a significant reduction in the number of synapses in the neuropil and an increase in the number of free dendritic spines. Many of these spines occurred in clusters, unapposed by glial processes. The effect on the synapse density was not due to a comparable increase in the area occupied by the added astrocytes or an increase in nerve terminal diameter. The results suggest that astrocytes alter the density of neuropil synapses and may also induce the sprouting of dendritic spines.

Animals↗
PubMed1982

Age-related changes in the neuropil in the rat inferior olive nucleus: quantitative electron microscopic study.

Age-related ultrastructural changes in the neuropil in the rat inferior olive nucleus were examined at 3, 6, 12, 18, 24 and 30 months old. The profiles of axon terminals, dendrites and astroglial processes from random samplings within the neuropil were traced. Subsequently, the percentages of these profiled areas in relation to the area of neuropil (relative volume fraction) were examined using the image analyzer system. The relative volume fractions of both axon terminals and dendrites in relation to the neuropil were found to have decreased in the aged rats, while the relative volume fraction of astroglial processes had progressively increased with aging.

Aging↗