Abstract
The topographic distribution of dopamine (DA) uptake, choline uptake, choline acetyltransferase (ChAT) activity and GABA uptake within the striata of weaver mutant mice and control mice was determined. Uptake of [3H]dopamine, [3H]choline and [14C]GABA, as well as ChAT activity were determined in samples prepared from the dorsolateral, dorsomedial, ventrolateral and ventromedial portions of the striatum. In 45–60 day old control mice, dopamine uptake was homogeneously distributed throughout the striatum. On the other hand, striata from weaver mice exhibited an uneven distribution with the ventral aspects having greater uptake activity than the dorsal regions. Thus, although the ventral portion of the striatum is less severely affected than the dorsal portion, all areas of the striatum exhibited significantly reduced uptake rates. In 9 and 12 month old mice, choline uptake was higher in lateral than medial zones of the striatum of both genotypes and no differences were observed between genotypes. GABA uptake was higher in the ventral striatum than in the dorsal striatum but again no differences were found between weaver and control mice. The results of this study indicate that the entire weaver striatum is severely deficient in its ability to recapture dopamine and thus is functionally compromised. The results also indicate that the striatal cholinergic and GABAergic interneurons are not directly or indirectly affected by the weaver gene.
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Sidman, R. L., Green, M. C., and Appel, S. H. 1965. Catalog of the neurological mutants of the mouse. Pages 66–67, Harvard University Press, Cambridge, MA.
Lalonde, R. 1986. Acquired immobility response in weaver mutant mice. Exp. Neurol. 94:808–811.
Lalonde, R. 1987. Motor abnormalities in weaver mutant mice. Exp. Brain Res. 65:479–481.
Lalonde, R., and Boetz, M. I. 1986. Navigational deficits in weaver mutant mice. Brain Res. 398:175–177.
Lalonde, R. 1986. Delayed spontaneous alternation in weaver mutant mice. Brain Res. 398:178–180.
Triarhou, L. C., and Ghetti, B. 1987. Neuroanatomical substrate of behavioral impairment in weaver mutant mice. Exp. Brain Res. 68:434–436.
Lane, P. W. 1964, Mouse News Letter 30:32.
Rakic, P., and Sidman, R. L. 1973. Sequence of developmental abnormalities leading to granule cell deficit in cerebellar cortex of weaver mutant mice. J. Comp. Neurol. 152:103–132.
Sidman, R. L. 1968. Development of interneuronal connections in brains of mutant mice. Pages 163–193,in Carlson, F. D. (ed.), Physiological and biochemical aspects of nervous integration. Prentice-Hall, Englewood Cliffs, NJ
Black, I. B. 1976. Abnormal brain catecholamine enzymes in weaver mutant mice. Brain Res. 105:602–605.
Lane, L. D., Nadi, N. S., McBride, W. J., Aprison, M. H., and Kusano, K. 1977. Contents of serotonin, norepinephrine and dopamine in the cerebrum of the ‘staggerer’, ‘weaver’ and ‘nervous’ neurologically mutant mice. J. Neurochem. 29:349–350.
Schmidt, M. J., Sawyer, B. D., Perry, K. W., Fuller, R. W., Foreman, M. M., and Ghetti, B. 1982. Dopamine deficiency in the weaver mutant mouse. J. Neurosci. 2:376–380.
Gupta, M., Felten, D. L. and Ghetti, B. 1987. Selective loss of monoaminergic neurons in weaver mutant mice-an immunocytochemical study. Brain Res. 402:379–382.
Triarhou, L. C., Norton, J., and Ghetti, B. 1988. Mesencephalic dopamine cell decifit involves areas A8, A9 and A10 in weaver mutant mice. Exp. Brain. Res. 70:256–265.
Roffler-Tarlov, S., and Graybiel, A. M. 1984. Weaver mutation has differential effects on the dopamine-containing innervation of the limbic and nonlimbic striatum. Nature (London) 307:62–66.
Kaseda, Y., Ghetti, B., Low, W. C., Richter, J. A., and Simon, J. R. 1987. Dopamine D2 receptors increase in the dorsolateral striatum of weaver mutant mice. Brain Res. 422:178–181.
Pullara, J. M., and Marshall, J. F. 1989. Striatal dopamine innervation and receptor density: regional effects of the weaver mutation. Brain Res. 480:225–233.
Kaseda, Y., Ghetti, B., Low, W. C., Norton, J., Brittain, H., Triarhou, L. C., Richter, J. A., and Simon, J. R. 1990. Agerelated changes in striatal dopamine D2 receptor binding in weaver mice and effects of ventral mesencephalic grafts. Exp. Brain Res. 83:1–8.
Simon, J. R. 1982. Cortical modulation of cholinergic neurons in the striatum. Life Sci. 31:1501–1508.
Fonnum, F. 1969. Radiochemical microassays for the determination of choline acetyltransferase and acetylcholinesterase activities. Biochem. J. 115:465–472.
Lowry, O. H., Rosebrough, N. J., Farr, L., and Randall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–274.
Tassin, J. P., Cheramy, A., Blanc, G., Thierry, A. M., and Glowinski, J. 1976. Topographical distribution of dopaminergic innervation and of dopaminergic receptors in the rat striatum. I. Microestimation of [3H]dopamine uptake and dopamine content in microdiscs. Brain Res. 107:291–301.
Rea, M. A., and Simon, J. R. 1981. Regional distribution of cholinergic parameters within the rat striatum. Brain Res. 219:317–326.
Fonnum, F., Walaas, I., and Iversen, E. 1977. Localization of GABAergic, cholinergic and aminergic structures in the mesolimbic system. J. Neurochem. 29:221–230.
Fonnum, F., Gottesfeld, Z., and Grofova, I. 1978. Distribution of glutamate decarboxylase, choline acetyltransferase and aromatic amino acid decarboxylase in the basal ganglia of normal and operated rats. Evidence for striatopallidal, striatoentopeduncular and striatonigral GABAergic fibers. Brain Res. 143:125–138.
Björklund, A., and Lindvall, O. 1984. Dopamine-containing systems in the CNS. Pages 55–122,in Björkland, A. and Hökfelt, T. (eds.) Handbook of Chemical Neuroanatomy, Vol. 2. Elsevier, Amsterdam.
Roffler-Tarlov, S., Pugatch, D., and Graybiel, A. M. 1990. Patterns of cell and fiber vulnerability in the mesostriatal system of the mutant mouse weaver. II. High affinity uptake sites for dopamine. J. Neurosci. 10:734–740.
Doucet, G., Brundin, P., Seth, S., Murata, Y., Strecker, R. E., Triarhou, L. C., Ghetti, B., and Björklund, A. 1989. Degeneration and graft-induced restoration of dopamine innervation in the weaver mouse neostriatum: a quantitative radioautographic study of [3H]dopamine uptake. Exp. Brain Res. 77:552–568.
Roffler-Tarlov, S., and Graybiel, A. M. 1987. The postnatal development of the dopamine-containing innervation of dorsal and ventral striatum: effects of the weaver gene. J. Neurosci. 7:2364–2372.
McGeer, P. L., McGeer, E. G., Fibiger, H. C., and Wickson, V. 1971. Neostriatal choline acylase and acetylcholinesterase following selective brain lesions. Brain Res. 35:308–314.
Kasa, P. 1986. The cholinergic systems in brain and spinal cord. Progr. in Neurobiol. 26:211–272.
Yu, H., Ghetti, B., and Simon, J. R. 1991. Changes in striatal glutamic acid decarboxylase activity in weaver mutant mice. Society for Neuroscience Abstracts 17:505.
Segovia, J., and Garcia-Munoz, M. 1987. Changes in the activity of GAD in the basal ganglia of the rat after striatal dopaminergic denervation. Neuropharmacology 26:1449–1451.
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Special ïssue dedicated to Dr. Morris H. Aprison
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Simon, J.R., Ghetti, B. Topographic distribution of dopamine uptake, choline uptake, choline acetyltransferase, and GABA uptake in the striata of weaver mutant mice. Neurochem Res 17, 431–436 (1992). https://doi.org/10.1007/BF00969888
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DOI: https://doi.org/10.1007/BF00969888