FENS Forum of European Neuroscience edition:7 location:Amsterdam date:3 - 7 July 2010
Since the discovery of metabotropic glutamate receptors (mGluRs) some 20 years ago, these modulatory receptors have received much attention as possible drug targets for a variety of neuropathological conditions. Group III mGluRs are expressed in limbic system nuclei and have been associated with inhibition of glutamatergic and/or GABAergic processes. However, it seems that group III subtypes are not evenly distributed throughout the CNS. mGluR4 is highly expressed in cerebellar granule cells, but can also be detected in olfactory bulb, amygdala, striatum. mGluR7 is expressed in very low levels in cerebellum, although it is the most widely distributed subtype of group III. mGluR8 is primarily expressed in olfactory bulb, cerebellum, hippocampus, mammilary body, striatum and lateral nucleus of the thalamus. These different distribution patterns suggest functional differences between the subtypes.
To investigate a possible functional differentiation between three mGluR group III subtypes, mGluR4, mGluR7 and mGluR8 subtype-specific knockout mice (backcrossed to C57BL/6 background) and their respective littermates were tested simultaneously in the same multimetric test battery. This battery included elements of neuromotor performance, exploratory behaviour, and learning and memory ability. In general, the lack of mGluR4, mGluR7 and mGluR8 did not cause any gross alterations in neuromotor and exploratory behaviours. On learning and memory-related tasks, mGluR7 knockout mice showed a reduced behavioural capacity on hippocampus-related tasks. More subtle differences were detected for mGluR4 knockout animals, while we observed no differential behavioural phenotype in mGluR8 deficient mice.
Funding: Fund for Scientific Research Flanders (HG).