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Abstract
mGluR8 is a G-protein coupled metabotropic glutamate receptor expressed in the mammalian
brain. Members of the mGluR family have been shown to be modulators of neural plasticity
and learning and memory. Here we analyze the consequences of a null mutation at the
mGluR8 gene locus generated using homologous recombination in embryonic stem cells
by comparing the learning performance of the mutants with that of wild type controls
in the Morris water maze (MWM) and the context and cue dependent fear conditioning
(CFC). Our results revealed robust performance deficits associated with the genetic
background, the ICR outbred strain, in both mGluR8 null mutant and the wild type control
mice. Mice of this strain origin suffered from impaired vision as compared to CD1
or C57BL/6 mice, a significant impediment in MWM, a visuo-spatial learning task. The
CFC task, being less dependent on visual cues, allowed us to reveal subtle performance
deficits in the mGluR8 mutants: novelty induced hyperactivity and temporally delayed
and blunted responding to shocks and temporally delayed responding to contextual stimuli
were detected. The role of mGluR8 as a presynaptic autoreceptor and its contribution
to cognitive processes are hypothesized and the utility of gene targeting as compared
to pharmacological methods is discussed.