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Biomedical subjects

A L Leiman

Publications and source records attributed to A L Leiman.

At least 19 recordsLinked to original sources
PubMed1994

Morphological correlates of altered neuronal activity in organotypic cerebellar cultures chronically exposed to anti-GABA agents.

Organotypic cerebellar cultures derived from newborn mice were chronically exposed to medium containing picrotoxin or bicuculline from explanation until they were recorded from extracellularly or fixed for morphological studies. Cultures exposed to anti-GABA agents for 13-18 days in vitro had decreased spontaneous cortical discharge rates when compared with sister control cultures and prolonged inhibitory responses to cortical stimulation. Electron microscopic examination of exposed cultures after 14-16 days in vitro revealed a hyperinnervation of Purkinje cell somata by inhibitory terminals predominantly of basket cell origin. The sprouted terminals penetrated otherwise intact Purkinje cell astrocytic sheaths. These changes represent a departure from the usual developmental pattern, a departure induced by exposure to anti-GABA agents that increased neuronal activity early in the development of the cerebellar circuitry in vitro. The precise signals that initiated the changes are unknown, but the altered development is most likely in response to increased Purkinje cell activity.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

Cytosine arabinoside effects in mouse cerebellar cultures in the presence of astrocytes.

Organotypic cerebellar cultures derived from neonatal mice were exposed to recent preparations of cytosine arabinoside that destroyed oligodendrocytes and drastically reduced granule cells, but did not reduce the astrocyte population. The cultures were analysed by light and electron microscopy, and by extracellular electrophysiological recording. Purkinje cells survived in greater numbers than in untreated explants and sprouted excess recurrent axon collaterals that formed heterotypical synapses with Purkinje cell dendritic spines. These changes were similar to those found in earlier studies with a cytosine arabinoside preparation that did reduce the astrocyte population, in addition to destroying oligodendrocytes and granule cells. Results with recent cytosine arabinoside preparations that differed from those obtained previously included astrocytic ensheathment of Purkinje cells and apposition of many unattached dendritic spines, encasement of heterotypical synapses by astroglial processes, a loss of Purkinje cell somatic spines, and a lack of somatic hyperinnervation of Purkinje cells by sprouted recurrent axon collateral terminals. All of these differences were attributed to the presence of adequate numbers of competent astrocytes. Heterotypical synapses formed by sprouted recurrent axon collateral terminals and Purkinje cell dendritic spines were functional, as indicated by cortical inhibition in response to antidromic Purkinje cell activation in the absence of somatic hyperinnervation. These results give further definition to the role of astrocytes in cerebellar development and plasticity.

Animals↗
PubMed1986

Influence of subcortical neurons on the functional development of cerebral neocortex in tissue culture.

The role of subcortical input and/or output pathways in the development of cortical networks was examined in organotypic tissue cultures derived from neonatal mouse brain. Comparisons were made between cultures of cerebral neocortex grown with large amounts of subcortical tissue and those that were completely isolated or included small amounts of subcortical tissue. Extracellular electrophysiological recordings showed differences in excitability and spatial distribution of responses elicited by electrical stimulation of the dorsal edge of cerebral neocortex. Cultures with proportionately greater amounts of subcortical tissue showed enhanced cortical excitability and also displayed a sharper columnar arrangement than was evident in explants that were completely isolated from subcortical influences. The data suggest that subcortical inputs and/or target fields may provide signals that influence the progressive functional development of cerebral neocortical circuitry.

Animals↗
PubMed1985

Evidence against neurotransmitter mediation of sprouting in granuloprival cerebellar cultures.

Cerebellar cultures derived from neonatal mice undergo a remarkable sprouting of Purkinje cell recurrent axon collaterals after exposure for the 1st 5 days in vitro to cytosine arabinoside to destroy granule cells. Such cultures were simultaneously exposed to large concentrations of the putative neurotransmitters glutamate and GABA, with subsequent continued exposure to the amino acids until the time of fixation at 15 or 16 days in vitro. Axon collateral sprouting was not prevented by glutamate or GABA, suggesting the sprouting is not mediated by the relevant neurotransmitters, but is more likely due to an alteration or lack of development of some trophic interaction between granule cells and their target Purkinje cells.

Animals↗
PubMed1985

Cerebellum plus locus coeruleus in tissue culture: I. Catecholamine histofluorescence and extracellular electrophysiology.

Neonatal mouse cerebellar cultures with incorporated dorsal pons contained groups of catecholamine histofluorescent locus coeruleus neurons that projected axons to cerebellar cortical regions. Electrical stimulation of local areas of the dorsal pontine fragments evoked complex inhibitory extracellular cortical responses that resembled cerebellar cortical responses to locus coeruleus stimulation in vivo. The apparent structural and functional integrity of the coeruleo-cerebellar system in tissue culture indicates that this model might reasonably be used for biochemical studies of catecholamine development and metabolism.

Animals↗
PubMed1983

Climbing fibers in mouse cerebellum co-cultured with inferior olive.

Cerebellar explants derived from neonatal mice were co-cultured with medulla containing inferior olive. The explants exhibited extracellular climbing fiber-like responses to electrical stimulation. On ultrastructural examination, many terminals with a high packing density of round, clear vesicles in a dark filamentous cytoplasm were present. Similar terminals, characteristic of climbing fibers, had not been identified in previous studies with cerebellar explants incorporating dorsal pons, but excluding medulla. The climbing fiber terminals formed appropriate synapses with Purkinje cell dendritic spines. The findings suggest that when climbing fibers are introduced into cerebellar cultures, accurate functional and morphological units are established.

Animals↗
PubMed1983

Reorganization in granuloprival cerebellar cultures after transplantation of granule cells and glia. I. Light microscopic and electrophysiological studies.

Granuloprival cerebellar cultures were transplanted after 9 or 16 days in vitro with cerebellar explants that had been exposed to kainic acid. The latter contained granule cells and differentiated glia, elements lacking in granuloprival cultures. Changes induced by transplantation observed by light microscopy included interposition of granule cells among the large cortical neurons of host explants; a reduction of the excess neurites of the Purkinje cell axon collateral system that is characteristic of granuloprival explants; and the appearance of myelinated fibers in previously unmyelinated cultures. The most notable electrophysiologic consequence of transplantation was the disappearance of inhibition of cortical spontaneous activity in response to antidromic stimulation of Purkinje cell axons, correlating with the disappearance of excess neurites, and suggesting that Purkinje cell recurrent collateral inhibition was no longer the dominant mode of cortical inhibition. Restoration of missing elements in granuloprival cultures incited development of structural and functional characteristics resembling those of normal cerebellar explants.

Animals↗
PubMed1980

Cytosine arabinoside effects on developing cerebellum in tissue culture.

Cerebellar explants derived from neonatal mice were exposed to cytosine arabinoside, an inhibitor of DNA synthesis. Following such exposure, the cortical regions of the explants contained numerous closely packed large neurons with few intervening elements and without lamination. The surviving large cortical neurons included Golgi cells and Purkinje cells, the latter with persistent dendritic spines in the absence of granule cells. A marked increase in density of subcortical and intracortical neurites was evident in fiber stains. The neurites were identified as Purkinje cell axons and axon collaterals by fiber tracing. Myelin failed to form around the axonal elements. Both regular and phasic spontaneous discharges were recorded electrophysiologically. Trains of cortical stimuli elicited both excitatory and inhibitory responses in the absence of parallel fibers. Antidromic stimulation of Purkinje cell axons evoked inhibition of spontaneous cortical discharges. By contrast, antidromic activation of Purkinje cell axons in control cultures had no effect on spontaneous cortical discharges, or provoked a transient increase in discharge rate. These responses were interpreted as consistent with a cortical remodeling in granuloprival cerebellar cultures in which basket-stellate cell inhibition of Purkinje cells was preempted by Purkinje cell recurrent axon collateral inhibition.

Animals↗
PubMed1979

Toxic effects of kainic acid on mouse cerebellum in tissue culture.

Cultures of mouse cerebellum were exposed for various intervals after explantation to kainic acid, a glutamic acid analog. Purkinje cells and intracerebellar nucleus neurons were destroyed and cortical laminar formation was inhibited by exposure to kainic acid, while granule cells were relatively spared. Prolonged kainate treatment also reduced the granule cell population. The destructive effects of kainic acid were evident upon exposure of Purkinje cells prior to the development of parallel fiber-Purkinje cell synapses, the neurotransmitter for which is believed to be glutamic acid. Glutamate application to intracerebellar nucleus neurons in vitro did not evoke extracellularly recorded excitatory effects, suggesting that these kainate-sensitive neurons do not have significant numbers of glutamate receptors. The combination of these observations suggests that neuronal toxic effects of kainic acid are not exclusively mediated by action on glutamate receptors, but involve other, less specific mechanisms as well.

Animals↗
PubMed1976

Neuroelectric blocking factors in multiple sclerosis and normal human sera.

Serum samples from 13 multiple sclerosis (MS) patients and ten normal human serum samples were applied to cerebral neocortex cultures and evaluated for their ability to block evoked electric activity. A high proportion of sera positive for neuroelectric blocking factors was found in both groups, and there was no substantial difference between serum samples from MS patients and those from normal human volunteers. Some of the neuroelectric blocking factors were thermolabile, others were thermostable, and still others may have been complement-dependent. It is concluded that the ability to block evoked electric responses in tissue cultures is a nonspecific serum property, and that it is not specifically related to the pathogenesis of demyelinating disease.

Adult↗
PubMed1975

Myelination inhibiting and neuroelectric blocking factors in experimental allergic encephalomyelitis.

Sensitization of Lewis rats with whole central nervous system tissue or with purified myelin induced both experimental allergic encephalomyelitis (EAE) and a serum factor which inhibited myelin formation in vitro. Sensitization with the encephalitogenic factor, myelin basic protein, induced EAE, but not the myelination inhibition factor. Sensitization with cerebroside induced neither EAE nor myelination inhibition factor. The serums from control animals without EAE as well as from animals sensitized with all of the above antigens blocked evoked electrical responses in vitro.

Animals↗