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M W Vogel

Publications and source records attributed to M W Vogel.

27 records · Page 2Linked to original sources
PubMed1996

CGP 39653 binding in the chick CNS after NMDA receptor antagonist treatment.

To analyze the affect of blocking neuronal activity on NMDA receptor levels during development, we have injected chick embryos with the competitive NMDA receptor antagonist NPC 12626 from E17 to E19. Brains from drug-treated (n = 7) and control (n = 6) embryos (E20) were processed for receptor autoradiography using the NMDA competitive antagonist [3H]CGP 39653. NPC 12626 treatment caused a significant 24 to 46% increase in [3H]CGP 39653 binding in both the forebrain and cerebellar cortex. The results support the hypothesis that NMDA receptor levels are regulated by activity-dependent mechanisms.

2-Amino-5-phosphonovalerate↗
PubMed1995

Purkinje cell dendritic arbors in chick embryos following chronic treatment with an N-methyl-D-aspartate receptor antagonist.

The normal development of Purkinje cell dendrites is dependent on afferent innervation. To investigate the role of neuronal activity in Purkinje cell dendritic development, chick embryos were chronically treated with a potent, selective, and systemically active competitive N-methyl-D-aspartate (NMDA) receptor antagonist, NPC 12626. The NMDA receptor was chosen as a target for pharmacological blockade because of the importance of the NMDA receptor in synaptic plasticity and stabilization in development. Chick embryos were given daily injections of NPC 12626 (25 to 100 mg/kg) from embryonic day 14 (E14) to E17. The initial injections of NPC 12626 dramatically blocked embryo movements, but activity levels partially recovered following subsequent injections. Embryo movements were reduced by 24% at the end of the experiment. Embryos were killed on E18, and their brains processed for Golgi-Cox staining. The morphology of Golgi-stained Purkinje cells in drug-treated embryos was similar to control embryos. Morphometric analysis showed, however, that chronic treatment with NPC 12626 resulted in a 19% reduction in Purkinje cell dendritic tree area and a 13% reduction in the number of dendritic branch points. The overall width and height of the drug-treated dendritic trees were not significantly different from controls, suggesting that NPC 12626 reduced Purkinje cell dendritic area by interfering with branch formation. The volume of the granule cell layer and the heights of the molecular and external granule cell layers was not reduced, suggesting that NPC 12626 treatment did not simply delay development. These results suggest that activation of the NMDA receptor may mediate the afferent-target interactions in the cerebellum that regulate the elaboration of Purkinje cell dendrites.

Amino Acids↗
PubMed1994

Topographic spinocerebellar mossy fiber projections are maintained in the lurcher mutant.

A variety of recent studies of cerebellar development have focused attention on the role of Purkinje cells as organizing elements for the topography of afferent fiber connectivity in the cerebellum. We have investigated the involvement of Purkinje and granule cells in the maintenance of topographic spinocerebellar mossy fiber projections by analyzing the distribution of spinocerebellar mossy fiber terminals in lurcher (+/Lc) mutant mice. Purkinje cells in the +/Lc mutant degenerate starting after the first week of postnatal development because of an intrinsic genetic defect. The loss of their Purkinje cell targets also results in the death of 90% of the granule cells. We examined the distribution of spinocerebellar mossy fiber terminals in the juvenile and adult +/Lc mutant to determine how the pattern of afferent projections is affected by the loss of Purkinje cells shortly after innervation of the cerebellum. Labeling of spinocerebellar mossy fiber terminals with WGA-HRP in the P38 and adult +/Lc mutant showed that, despite the loss of almost all Purkinje cells and 90% of the granule cells, spinocerebellar mossy fibers project to the appropriate folia and segregate into relatively normal parasagittal bands. While we cannot rule out the possibility that Purkinje cells may be involved in the initial establishment of topographic maps, our results indicate that Purkinje cells are not necessary for the maintenance of the normal spinocerebellar mossy fiber topographic map.

Animals↗
PubMed1993

A theoretical and experimental examination of cell lineage relationships among cerebellar Purkinje cells in the mouse.

In this paper, we continue our examination of the role of cell lineage in the development of the cerebellar Purkinje cell population of the mouse. The analysis of Purkinje cell lineage is based on counts of the number of wild-type Purkinje cells in +/Lc<==>wild-type chimeras. +/Lc Purkinje cells undergo a cell autonomous degeneration early in postnatal development leaving variable numbers of wild-type Purkinje cells in chimeric animals. Using theoretical, statistical, and experimental approaches, we have tested various developmental models to account for the numerical development of Purkinje cell numbers in the +/Lc<==>wild-type chimeras. We have analyzed models based on the assumption that cell lineages are irrelevant to Purkinje cell development, as well as our own previous hypothesis that Purkinje cells descend from a small number of progenitor cells selected during the early stages of neurogenesis. The theoretical approach calculates the distributions of Purkinje cell numbers in hypothetical +/Lc<==>wild-type chimeras and inbred mice based on both clonal and nonclonal hypotheses of neuronal development. Variations of the model are compared with published cell counts from +/Lc<==>C3H/HeJ, +/Lc<==>C57BL/6J, +/Lc<==>AKR/J chimeras, and C3H/HeJ inbred mice. The statistical approach assesses the significance of the fits of the observed data with different variations of the model by Monte Carlo simulation techniques. The results of the comparison suggest that our observed data is more likely to be explained by a clonal model of development than by alternate models in which cell lineages play a minor role. Our experimental approach describes a new +/Lc<==>C3H/HeJ chimera in which all of the Purkinje cells (> 7900) are found on one side of the brain. We have analyzed this chimera with respect to clonal and nonclonal models of Purkinje cell development. The extreme asymmetric distribution of Purkinje cells provides added support to the hypothesis that there is a small number of progenitor cells that generate Purkinje cells. Our findings lead to the conclusion that while not all alternate models of mammalian CNS development can be completely excluded, the early progenitor hypothesis is the most probable model of Purkinje cell development.

Animals↗
PubMed1991

Cerebellar Purkinje cells provide target support over a limited spatial range: evidence from lurcher chimeric mice.

The distribution of Purkinje cells, granule cells, and olivary neurons was quantitatively analyzed in a lurcher +/Lc in equilibrium C3H/HeJ chimera in which the surviving wild type Purkinje cells were unilaterally distributed in the left hemicerebella. The left hemisphere of this mouse contains 7600 Purkinje cells, approximately 10% of the number of Purkinje cells in inbred C3H/HeJ mice. The right hemisphere contains 300 Purkinje cells, all of which are found within 200 microns of the midline. As in other +/Lc in equilibrium wild type chimeras, the ratio of granule cells to Purkinje cells is increased in the left hemisphere, reflecting increased granule cell survival. In the right hemisphere, however, the number of granule cells is reduced to that found in +/Lc mutants. In the inferior olive, almost twice as many neurons are found in the right nucleus as opposed to the left nucleus. As the projections of olivary neurons are crossed, the number of olivary neurons is increased in the nuclei that project to the cerebellar hemisphere containing Purkinje cells compared to the olivary nuclei that project to the cerebellar hemisphere with almost no Purkinje cells. The preferential survival of granule cells and olivary neurons that either occupy or project to the hemicerebellum containing Purkinje cells suggests that the availability of trophic support from target Purkinje cell neurons is spatially restricted.

Animals↗
PubMed1989

Numerical matching in the mammalian CNS: lack of a competitive advantage of early over late-generated cerebellar granule cells.

In this report we use postnatal 3H-thymidine injections to test whether granule cells that are generated early in postnatal cerebellar development and whose axons have access to their Purkinje cell target beginning in the first postnatal week have an advantage over granule cells generated 9 days later in the competition for target-related stabilization. In the wild-type mouse, 3-5% of the adult granule cell population is labeled by injection of 3H-thymidine at either postnatal day 4 (P4) or P13. In the lurcher mutant, however, over 40% of the surviving granule cells are labeled by P4 injection while less than 1% are labeled after a P13 injection. Together, these results suggest that time of target contact is a critical factor in the competition for neuronal survival. The results from the lurcher chimeras, however, reveal that the situation is likely to be more complicated. In all chimeras examined, with target sizes ranging from 3 to 108% of wild type, equivalent numbers of granule cells were labeled at P4 and P13. These data lead to the contradictory conclusion that, in this experimental situation, early generated granule cells do not have a competitive advantage over later-generated granule cells. The results are discussed in terms of various models of target stabilization. We propose that, of the various hypotheses, our results are best explained by postulating two distinct mechanisms for developmental cell death. Supporting evidence for this hypothesis from other neuronal systems is also briefly reviewed.

Animals↗
PubMed1989

Numerical matching between granule and Purkinje cells in lurcher chimeric mice: a hypothesis for the trophic rescue of granule cells from target-related cell death.

Previous studies of wild-type mice or mutant-wild-type mouse chimeras using the neurological mutant staggerer have supported a numerical matching hypothesis for target-related cell death. However, analyses of chimeras of a second neurological mutant, lurcher, have suggested that there may be significant flexibility in the relationship between the numbers of pre- and postsynaptic neurons. Whereas in staggerer chimeras there is a strict proportionality between the number of cerebellar granule cells and their postsynaptic target, the Purkinje cells, in lurcher chimeras, Wetts and Herrup (1983) report a relative increase in granule cell survival. We have reexamined the numerical matching between Purkinje and granule cells in an additional 5 lurcher----wild-type and 4 wild-type----wild-type chimerase. Our findings confirm and extend the results of the previous study to show that there is a close correlation between the number of granule and Purkinje cells in +/Lc chimeras, but for any given number of Purkinje cells in the +/Lc chimeras, more granule cells survive than in staggerer chimeras or inbred mouse strains. Whereas the ratio of granule to Purkinje cells in staggerer chimeras or inbred mouse strains is constant across all target sizes, in +/Lc chimeras the ratio of granule cells to Purkinje cells increases as the number of target neurons decreases. It seems likely that the increased granule cell survival is somehow related to the delayed degeneration of the +/Lc fraction of target cells in the +/Lc chimeras. Among the possible explanations for the observed results, we favor the hypothesis that a trophic factor is produced in +/Lc chimeras in response to the deafferentation of Purkinje cells that is capable of rescuing granule cells from target-related cell death. Our preference is based, in part, on observations of the state of the dendritic tree of the wild-type Purkinje cells that survive in +/Lc chimeras (Caddy et al., 1986).

Animals↗
PubMed1987

Activation patterns of embryonic chick lumbosacral motoneurones following large spinal cord reversals.

1. Embryonic chick motoneurones were caused to innervate inappropriate hindlimb muscles by rotating the presumptive lumbosacral region of the neural tube in stage 15-16 embryos which is prior to the outgrowth of motoneurone axons. 2. The activation patterns of motoneurones in control and spinal cord reversal embryos were analysed from electromyographic (e.m.g.) recordings of stage 36 limb muscles during evoked movement sequences in an isolated spinal cord-limb preparation. Histograms representing the frequency of activation were constructed for each muscle. The muscle's pattern of activation was classified as flexor-like or extensor-like and compared to the activation patterns of control muscles. 3. A series of control operations was performed in which the prospective lumbosacral region of the neural tube was removed and replaced in its original orientation. Muscles in these embryos were innervated by their normal motoneurone pools and they were activated normally, indicating that the neural tube operation per se does not alter the activation pattern of motoneurones. Furthermore, some muscles (twelve out of sixty-one) in spinal cord reversal embryos had normal activation patterns and appeared to be innervated by their original motoneurones. Based on these results and the result of a previous study (Landmesser & O'Donovan, 1984 b), it is concluded that motoneurones in reversed spinal cords are activated in a manner appropriate for their original identity. 4. The majority of muscles (thirty-three out of sixty-one) in large spinal cord reversal embryos were activated during an appropriate phase of the kicking cycle. Of the remaining muscles, 16% were activated inappropriately (i.e. extensor muscles were activated as flexors, and vice versa), and 30% had a novel 'mixed' flexor- and extensor-like activation pattern. However, the activation pattern of most muscles differed markedly from that of any other control muscles regardless of whether the muscle was activated appropriately or inappropriately as a flexor or extensor. The abnormal activation patterns are a likely consequence of the diffuse distribution of inappropriate motoneurones projecting to foreign muscles in embryos with large spinal cord reversals. Since it is likely that motoneurones are still activated according to their original identity, the activation patterns of individual foreign motor units projecting to a muscle sum in e.m.g. recordings to produce a novel abnormal activation pattern.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗