Correlated quantitative studies of the neostriatum, nucleus accumbens, substantia nigra, and ventral tegmental area in normal and weaver mutant mice

Bayer, Shirley A.; Triarhou, Lazaros C.; Thomas, James; Ghetti, Bernardino

doi:10.1523/jneurosci.14-11-06901.1994

Cited by 23 publications

(8 citation statements)

References 38 publications

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“…2B) is easily observed when it is compared to the + / + SN ( Fig. 2A), confirming earlier quantitative studies (1,7). What is different in this report is that after [3H]thymidine injections begin on E12, many TH-immunoreactive neurons are still labeled with [3H]thymidine in the +/+ SN (Fig.…”

Section: Resultssupporting

confidence: 89%

Selective vulnerability of late-generated dopaminergic neurons of the substantia nigra in weaver mutant mice.

Bayer

Wills

Triarhou

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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In homozygous weaver (wv/wv) mutant mice, MATERIALS AND METHODSDeterminations of the Total Number of Dopaminergic Neurons in the Ventral Midbrain at Birth. The large breeding colony of mice carrying the weaver gene (wv) at Indiana University School of Medicine is maintained on a B6CBA-AWJ/A hybrid stock background and occasionally produces homozygous weaver males that are fertile. A fertile homozygous male was successfully paired with a homozygous female, and the three pups that were the offspring of this mating were killed on the day of birth by perfusion through the heart with 10% neutral buffered formalin. A litter of three wild-type (+/+) control pups was also killed on the day of birth in the same manner. The brains of both groups were cryoprotected in graded sucrose solutions (5%-30%) in phosphate buffer and were flash-frozen in isopentane cooled to -70°C in a dry-ice bath after they were positioned on microtome chucks on a pillow of cryostat mounting medium. Coronally cut serial sections (20 gm) were thaw-mounted on chrome alum/gelatincoated slides and were thoroughly dried at room temperature before immunocytochemistry for TH was performed as described (1).Neurons that were stained positively for the presence of TH in the ventral midbrain indicated those that were dopaminergic. The determination of the total numbers of dopaminergic neurons involved three steps in each of the 6 animals. First, all TH stained neurons were counted unilaterally in the retrorubral field/SN pars compacta continuum, and the ventral tegmental area/interfascicular nucleus continuum. Second, the area of nuclear profiles in TH stained neurons was determined with a Quantimet 570 (Leica, Cambridge, U.K.) image-processing and -analysis system that is fitted to an Aristoplan microscope. Control of the image-analysis system and the automated microscope is achieved with the standard Quantimet 570 QUIC and QBASIC software written in the QBASIC language. Immunopositive structures were detected in a binary plane with Quantimet's gray-scale detection function. After performing minor corrections, the areas of randomly selected nuclear profiles were measured automatically (150 nuclei for the retrorubral field/SN pars compacta continuum and 100 nuclei for the ventral tegmental area/interfascicular nucleus continuum). The areas were converted to square microns, and nuclear diameters were calculated in micrometers. Third, the total number of dopaminergic neurons in each continuum was determined from the cell-count data and the nuclear-area data by using a modification of the Abercrombie method (1). The grand total of all dopaminergic neurons in the ventral midbrain (Table 1) tTo whom reprint requests should be addressed at:

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Section: Resultssupporting

confidence: 89%

Selective vulnerability of late-generated dopaminergic neurons of the substantia nigra in weaver mutant mice.

Bayer

Wills

Triarhou

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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“…The interest in devising restorative therapies for patients suffering from these diseases in part motivates elucidation of the cues involved in the formation of this pathway. The MTp originates in DA neurons in the ventral mesencephalon (VM) whose axons grow rostrally to traverse the diencephalon in a large but well-defined pathway, the medial forebrain bundle (MFB), and reach the telencephalon to synapse on neurons in the nucleus accumbens (mesolimbic pathway) and the striatum (mesostriatal pathway) (Altman and Bayer, 1981; Bayer et al, 1994; Bayer et al, 1995; Voorn et al, 1988). A much smaller group of DA axons originates in rostral cells of the VM, branches off the MFB at the mesencephalon-diencephalon boundary and gives rise to the meso-habenular pathway (MHp) whose axons run along the fasciculus retroflexus and synapse on the lateral habenula (Phillipson and Griffith, 1980; Skagerberg et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Expression by midbrain dopamine neurons of Sema3A and 3F receptors is associated with chemorepulsion in vitro but a mild in vivo phenotype

Torre

Gutekunst

Gross

2010

Molecular and Cellular Neuroscience

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Here we explore the role of semaphorin 3A and 3F (Sema3A, Sema3F) in the formation of the mesotelencephalic pathway. We show that Sema3A and 3F are expressed in the ventral mesencephalon (VM) of E13.5 rat embryos; the receptors Neuropilin 1 and Neuropilin 2, and coreceptors L1CAM, NrCAM, and Plexins A1 and A3 but not A4 are expressed by VM dopaminergic neurons; these neurons bind Sema3A and 3F in vitro which induces collapse of their growth cones and elicits, with different potencies, a repulsive response; and this response is absent in axons from Nrp1 and Nrp2 null embryos. Despite these in vitro effects, only very mild anatomical defects were detected in the organization of the mesotelencephalic pathway in embryonic and adult Nrp1 or Nrp2 null mice. However, the dopaminergic meso-habenular pathway and catecholaminergic neurons in the parafascicular and paraventricular nuclei of the thalamus were significantly affected in Nrp2 null mice. These data are consistent with a model whereby Sema3A and 3F, in combination with other guidance molecules, contributes to the navigation of DA axons to their final synaptic targets.

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“…Homozygous weaver mice (wv/wv) have a severe reduction in the dopamine (DA) content and tyrosine hydroxylase (TH) activity of the neostriatum which are associated with reduction of TH-positive neurons in the substantia nigra (SN), retrorubral nucleus (RRN), and ventral tegmental area (VTA) (Schmidt et al 1982;Roffler-Tarlov and Graybiel 1984;Triarhou et al 1986Triarhou et al , 1988Gupta et al 1987;Triarhou 1987;Roffier-Tarlov et al 1990;Richter et al 1992;Bayer et al 1994). The number of mesencephalic TH-positive cells in wv/wv appears normal at birth, becomes progressively lower postnatally, and, particularly in the SN, decreases by 85% by 2 years of age (Triarhou et al 1988;Triarhou 1990, 1992a,b,c;Bayer et al 1994Bayer et al , 1995Verney et al 1995). In the SN of wv/wv, the neurons that are immunopositive for both TH and calbindin-D28 k appear selectively spared (Gaspar et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Atrophy and loss of dopaminergic mesencephalic neurons in heterozygous weaver mice

et al. 1997

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The phenotypic effect of the weaver mutation in the ventral midbrain of homozygous mutants is associated with the progressive loss of dopaminergic neurons. To discover whether the number of mesencephalic dopaminergic cells is altered in weaver heterozygotes (wv/+), we studied mice between 20 and 365 days of age. We counted tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra (SN), retrorubral nucleus (RRN), and ventral tegmental area (VTA), and measured cross-sectional areas of neuronal somata in the SN of wv/+ and age-matched wild-type controls (+/+). The number of TH-positive cells in the wv/+ ventral midbrain was on average 13% lower than normal. Cell loss was detected selectively in the SN (12%) and VTA (23%). The areas of somatic profiles in the wv/+ nigral neurons were on average reduced by 9.8%. The neuronal losses in the SN and VTA correlated with a 13.8% reduction in dopamine level in the ventral striatum in wv/+ mice at 14-16 months of age. Our findings imply that a single dose of the weaver gene in the mouse is associated with cellular damage leading to a chronic deficiency in the mesostriatal dopaminergic system.

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Correlated quantitative studies of the neostriatum, nucleus accumbens, substantia nigra, and ventral tegmental area in normal and weaver mutant mice

Cited by 23 publications

References 38 publications

Selective vulnerability of late-generated dopaminergic neurons of the substantia nigra in weaver mutant mice.

Selective vulnerability of late-generated dopaminergic neurons of the substantia nigra in weaver mutant mice.

Expression by midbrain dopamine neurons of Sema3A and 3F receptors is associated with chemorepulsion in vitro but a mild in vivo phenotype

Atrophy and loss of dopaminergic mesencephalic neurons in heterozygous weaver mice

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