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  • Society for Neuroscience  (5)
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  • Society for Neuroscience  (5)
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  • 1
    Online Resource
    Online Resource
    Society for Neuroscience ; 1990
    In:  The Journal of Neuroscience Vol. 10, No. 3 ( 1990-03-01), p. 734-740
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 10, No. 3 ( 1990-03-01), p. 734-740
    Abstract: Weaver (gene symbol wv) is an autosomal recessive mutation in the mouse that causes the death of neurons in the cerebellum and of dopamine- containing neurons in the mid-brain. In the accompanying paper and in previous reports, the selective nature of the deficit produced by the gene in the dopamine-containing systems has been described after analysis of the patterns of the residual innervation in the striatum and the patterns of cell death in the midbrain. In the present report, we describe deficits in the terminals of the mesostriatal system occurring prior to a detectable dopamine deficiency in the striatum and prior to the onset of cell death in the mesencephalic dopamine- containing neurons during development. We have also found deficits in the remaining terminals of the adult weaver's striatum after the weaver pattern of innervation has been permanently established. Axonal terminals in the caudoputamen are impaired in weaver mice at postnatal day 7, before the onset of dopamine depletion in the caudoputamen and cell death in the midbrain. The impairment was revealed by a markedly deficient high-affinity uptake for 3H-dopamine by synaptosomes prepared from the caudoputamen. Throughout the remainder of development and in adulthood, the extent of the deficit in 3H-dopamine uptake was always greater than that for dopamine content. No striatal region was completely spared the effects of the gene. In the nucleus accumbens of the weavers, where dopamine content is normal, 3H-dopamine uptake was reduced by 35% in the synaptosomal preparations. In the olfactory tubercle, dopamine levels were reduced by 44% but 3H-dopamine uptake was reduced by 60%.(ABSTRACT TRUNCATED AT 250 WORDS)
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 1990
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Society for Neuroscience ; 1990
    In:  The Journal of Neuroscience Vol. 10, No. 3 ( 1990-03-01), p. 720-733
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 10, No. 3 ( 1990-03-01), p. 720-733
    Abstract: In mice carrying the autosomal recessive gene weaver, there is a massive postnatal loss of dopamine in the caudoputamen, the target of the nigrostriatal system, with relative (though not complete) preservation of dopamine in the ventral striatum, a target of the mesolimbic system. There is concomitant death of catecholaminergic neurons in the substantia nigra, with much less cell death in the limbic midbrain area. In the study reported here, we have reexamined the mesostriatal system of weaver mice by means of tyrosine hydroxylase (TH) immunohistochemistry in order to determine the local architecture of the defect within the striatum and substantia nigra. For the dorsal striatum, the most striking finding was the appearance in the weaver caudoputamen of small pockets of especially weak immunostaining within a larger dorsal zone of generally reduced TH-positive neuropil. These pockets were identified as striosomes by calbindin28k and met- enkephalin immunohistochemistry carried out on adjacent sections. In dorsal, central, and caudal sectors of the caudoputamen, there was also more generalized depletion of TH-immunoreactive neuropil. In the mid- brains of the mutants, the patterns of loss of TH-positive neurons appeared to correspond to these distributions of reduced immunostaining in the striatum. In the substantia nigra pars compacta, ventrally situated TH-positive neurons were especially affected, suggesting preferential depletion of TH-positive neurons projecting to striosomes. In addition, there was a central sector of nearly complete loss of TH- positive neurons in the substantia nigra para compacta and a marked depletion of TH-positive neurons in cell group A8 that, together, may have accounted for the diminution of TH-positive innervation of the striatal matrix. We conclude that the effects of the weaver gene discriminate among mesostriatal subsystems not only according to the regional affiliations of these subsystems within the dorsal and ventral striatum, but also according to the preferential association of the subsystems for the striosomal and matrical compartments of the caudoputamen. The depletion of TH-positive innervation was not confined to the dorsal striatum proper. The defect extended into the adjoining nucleus accumbens, where it appeared to affect the lateral “core” division, and included also a lateral part of the olfactory tubercle. Thus, as in the dorsal striatum, the defect in the TH-positive innervation of the ventral striatum closely follows the local architecture of this striatal region. Neuronal loss in the ventral tegmental area was not evident on qualitative analysis, but at the border between lateral cell group A 10 and medial cell group A9 there was obvious loss of immunostained neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 1990
    detail.hit.zdb_id: 1475274-8
    SSG: 12
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    Society for Neuroscience ; 1984
    In:  The Journal of Neuroscience Vol. 4, No. 5 ( 1984-05-01), p. 1343-1353
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 4, No. 5 ( 1984-05-01), p. 1343-1353
    Abstract: gamma-Aminobutyric acid (GABA) is the proposed neurotransmitter for four types of cerebellar neurons-Purkinje, Golgi, basket, and stellate neurons. With this investigation we have begun studies to establish when these neurons acquire their neurotransmitter “identification.” Autoradiographic studies of both cultured embryonic (embryonic day 13) cerebellar cells and of intact embryonic cerebellum (embryonic day 13) were conducted with tritiated GABA. Two to 5% of the embryonic cerebellar cells accumulated [3H]GABA in vitro. By morphological and immunocytochemical criteria, labeled cells were large neurons with either a thick, apical process, a multipolar shape, or were bipolar with longer processes. The identification of cells which accumulated [3H] GABA as neuronal precursors was supported by the differential sensitivity to drugs that preferentially inhibit accumulation of [3H]GABA by neurons and glia. The results of the in vitro experiments were confirmed and extended with in vivo experiments. When intact cerebellar tissue was removed at embryonic day 13, stripped of meninges and choroid plexus, exposed to low concentrations of [3H] GABA, and processed for light microscopic autoradiography, heavily labeled cells were seen in the middle of the cerebellar anlage. Labeled cells were not seen in the ventricular zone of proliferating neuroblasts lining the fourth ventricle or in the external granular layer emerging at the lateral aspect of the pial surface. The accumulation of [3H]GABA by these cells also showed the pharmacological characteristics of uptake by neurons. This study shows that among migrating, immature forms of the larger neurons of the embryonic cerebellum, there is a select group which accumulates [3H] GABA and other classes of cells which do not. These results indicate very early acquisition of transmitter expression by cerebellar neurons, far in advance of their final positioning and establishment of synapses.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 1984
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Society for Neuroscience ; 1996
    In:  The Journal of Neuroscience Vol. 16, No. 5 ( 1996-03-01), p. 1819-1826
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 16, No. 5 ( 1996-03-01), p. 1819-1826
    Abstract: The midbrain of the adult homozygous weaver (wv/wv) mouse is notable for a reduction in the numbers of dopamine-containing cells in the substantia nigra (A9) and the retrorubral nucleus (A8). We have determined that the reduction in tyrosine hydroxylase (TH)-positive neurons in the ventral midbrain of the weaver is attributable to the loss of neurons after postnatal day 7 (P7). Because the number and spatial distribution of TH-positive mesencephalic neurons in wv/wv, heterozygous weavers (+/wv), and wild-type mice are not significantly different on P7, we conclude that the early developmental steps of proliferation and migration have taken place normally in the mutant. Although numbers and distribution of cells are normal in the wv/wv on P7, the appearance of the TH-stained ventral midbrain is abnormal because of the paucity of TH-stained dendritic processes. The ventrally extending TH-positive dendrites are largely absent in the young wv/wv. The wv/wv also can be distinguished from both homozygous normal (+/+) and wv/wv littermates on P7 based on the appearance of dendrites that are more numerous than in the wv/wv but thin, disorganized, and sparse compared with +/+. Most cell death seems to take place in wv/wv before P21. However, at least one subset of dopamine-containing neurons disappears later. The zone of densely packed TH-positive neurons in the substantia nigra that is likely to be the origin of innervation to striosomes in the caudoputamen disappears between P21 and adulthood. Despite the early pathology evident in the mesencephalic dopamine- producing neurons of the +/wv, no evidence for cell death was observed there even in the oldest +/wv weavers studied.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 1996
    detail.hit.zdb_id: 1475274-8
    SSG: 12
    Location Call Number Limitation Availability
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  • 5
    Online Resource
    Online Resource
    Society for Neuroscience ; 1986
    In:  The Journal of Neuroscience Vol. 6, No. 11 ( 1986-11-01), p. 3319-3330
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 6, No. 11 ( 1986-11-01), p. 3319-3330
    Abstract: In an earlier report we presented evidence pointing to a differential effect of the mutant gene weaver on the dopamine-containing fiber systems innervating the striatum. In mice homozygous for the weaver mutation, there is a severe loss of dopamine in the caudoputamen, the main target of the nigrostriatal system. By contrast, dopamine is entirely conserved in the nucleus accumbens, a target of the mesolimbic system, and is moderately affected in the olfactory tubercle. The present study shows that these defects in dopamine are gene dose- dependent, that they are established by the end of the first month of life, and that the losses are permanent and not progressive. As in homozygous weavers, the greatest defects in striatal dopamine in heterozygous weavers occur in the dorsolateral caudoputamen and the lateral olfactory tubercle. The abnormalities in the striatal dopamine content of weaver mice are not accompanied by abnormalities in the turnover of dopamine, judging from measurements of the dopamine metabolite dihydroxyphenylacetic acid. Norepinephrine content is also normal in each striatal region. No deficits in striatal dopamine occur in mice homozygous for the mutant genes staggerer and Purkinje cell degeneration, which, like the weaver mutation, result in ataxia and cerebellar pathology. A survey of nonstriatal regions in the weaver mice showed that the effects of the weaver gene on the dopamine- containing innervation of the forebrain are not confined to striatal targets but also extend to the septum and the hypothalamus. By contrast, dopamine in the frontal cortex, the amygdala, the olfactory bulb, and the retina is entirely spared. The pattern and extent of loss of dopamine in the weaver forebrain is thus region- and system- specific. In confirmation of our initial findings, a ca. 30% depletion of dopamine occurs in the weaver midbrain, the region containing the cell bodies of origin of the mesostriatal dopamine systems. A comparison of histofluorescent sections through weaver and control midbrains revealed a reduction of catecholamine-containing neurons in the pars compacta of the weaver animals. These results point to a subpopulation of dopamine-containing neurons as primary targets of the weaver gene or as being closely associated with such primary targets. As a gene-dose effect has also been shown for the cerebellar granule cell loss in the weaver, the mutant gene must have at least 2 cellular targets. We suggest that the cerebellar and mesostriatal pathologies may be linked by a common molecular mechanism.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 1986
    detail.hit.zdb_id: 1475274-8
    SSG: 12
    Location Call Number Limitation Availability
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