Distribution of glutamate receptors of the NMDA subtype in brains of heterozygous and homozygous weaver mutant mice

In weaver mice, mutation of an G-protein inwardly rectifying K+ channel lea ds to a cerebellar developmental anomaly characterized by granule and Purki nje cell loss and. in addition, degeneration of dopaminergic neurons. To ev aluate other deficits, glutamate receptors sensitive to N-methyl-D-aspartat e (NMDA) were examined by autoradiography with [H-3]MK-801 in 36 brain regi ons from heterozygous (wv/+) and homozygous (wv/wv) weaver mutants, and com pared to wild type (+/+) mice. In wv/+ and wv/wv mutants labelling decrease d in cortical regions, septum, hippocampus, subiculum. neostriatum, nucleus accumbens, superior colliculus and in the cerebellar granular layer, The r eductions in [H-3]MK-801 binding were particularly specific in the cerebell ar granular layer of wv/wv mutants, but an ubiquitous altered NMDA receptor topology was revealed in other brain regions. Abnormal developmental signa ls, or aberrant cellular responses, may underlie widespread NMDA receptor r eductions, while in cerebellar cortex they could be lacking due to the mass ive loss of cerebellar granule cells.