Topology of ionotropic glutamate receptors in brains of heterozygous and homozygous weaver mutant mice.
In weaver mice, mutation of a G-protein inwardly rectifying K(+) channel leads to a cerebellar developmental anomaly characterized by granule and Purkinje cell loss and, in addition, degeneration of dopaminergic neurons. To evaluate other deficits, ionotropic glutamate receptors sensitive to N-methyl-D-aspartate (NMDA), amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and kainic acid (KA) were examined by autoradiography with [(3)H]MK-801, [(3)H]AMPA, and [(3)H]KA. These surveys were carried out in selected areas of cerebral cortex, hippocampus and related limbic regions, basal ganglia, thalamus, hypothalamus, brainstem, and cerebellum from heterozygous (wv/+) and homozygous (wv/wv) weaver mutants, and compared to wild-type (+/+) mice. In wv/+ and wv/wv mutants, NMDA receptor levels were lower in cortical areas, septum, hippocampus, subiculum, neostriatum, nucleus accumbens, superior colliculus, and in the cerebellar granular layer. Densities of KA receptors were lower in cortical areas, hippocampus, limbic system structures, neostriatum, nucleus accumbens, thalamus and hypothalamus, superior and inferior colliculi, and cerebellar cortex of wv/wv mutants. Levels of AMPA receptors in the weaver were higher than in +/+ mice, particularly in somatosensory and piriform cortices and periaqueductal gray of wv/+, and in somatosensory cortex, CA1 field of Ammon's horn and cerebellar granular layer of wv/wv. Abnormal developmental signals, aberrant cellular responses, or a distorted balance between neurotransmitter interactions may underlie such widespread and reciprocal glutamate receptor alterations, while in the case of cerebellar cortex, NMDA receptors are lacking due to a massive disappearance of cerebellar granule cells and some loss of Purkinje neurons.
Reader
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Centre de recherche en sciences neurologiques, Département de physiologie, Faculté de médecine, Université de Montréal, Montréal, Quebec, H3C 3J7 Canada. tomas.a.reader@umontreal.ca
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D000818:Animals; D001921:Brain / Q000378:metabolism*; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000235:genetics / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014018:Tissue Distribution
D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate