On the cellular localization of cerebellar muscarinic receptors: an autoradiographic analysis of weaver, reeler, Purkinje cell degeneration and staggerer mice.
Light microscopic autoradiography of [3H]quinuclidinyl benzilate binding sites was used to study the distribution of muscarinic cholinergic receptors in mouse mutants which have abnormalities affecting specific cerebellar cell types. In the normal C57BL/6J mouse, binding sites were distributed throughout the cerebellar cortex, with the highest levels in the granule cell layer and deep cerebellar nuclei. Normal binding site density was observed in the cerebellum of the weaver mutant in which the majority of granule cells had degenerated. The density of [3H]quinuclidinyl benzilate binding sites was elevated in the cortex of the reeler, despite a reduction in the number of granule cells. The concentration of binding sites was also high over the Purkinje cell masses where granule cells were largely absent. No significant reduction in cortical [3H]quinuclidinyl benzilate binding site density was detected in the Purkinje cell degeneration mutant, in which essentially all Purkinje cells had degenerated. In contrast, receptor binding in the deep cerebellar nuclei of this mutant was significantly increased. A substantial increase in labeling was observed in the cortex and deep nuclei of the staggerer cerebellum in which a large fraction of Golgi II cells, Purkinje cells, granule cells and mossy fibers have degenerated. We discuss the possibility that the persistence of [3H]quinuclidinyl benzilate binding sites in all four mutants may imply a non-neuronal localization for a large proportion of muscarinic receptors in the mouse cerebellar cortex.
Neustadt
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Department of Pharmacology, California College of Medicine University of California, Irvine 92717.
Frostholm
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Rotter
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D000818:Animals; D001345:Autoradiography; D002531:Cerebellum / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants / Q000378:metabolism*; D009410:Nerve Degeneration; D011689:Purkinje Cells / Q000502:physiology*; D011813:Quinuclidinyl Benzilate; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014018:Tissue Distribution; D014316:Tritium
D011976:Receptors, Muscarinic; D014316:Tritium; D011813:Quinuclidinyl Benzilate