IMPAIRED LONG-TERM POTENTIATION INDUCTION IN DENTATE GYRUS OF CALRETININ-DEFICIENT MICE

Calretinin (Cr) is a Ca2+ binding protein present in various populatio ns of neurons distributed in the central and peripheral nervous system s, We have generated Cr-deficient (Cr-/-) mice by gene targeting and h ave investigated the associated phenotype. Cr-/- mice were viable, and a large number of morphological, biochemical, and behavioral paramete rs were found unaffected. In the normal mouse hippocampus, Cr is expre ssed in a widely distributed subset of GABAergic interneurons and in h ilar messy cells of the dentate gyrus, Because both types of cells are part of local pathways innervating dentate granule cells and/or pyram idal neurons, we have explored in Cr-/- mice the synaptic transmission between the perforant pathway and granule cells and at the Schaffer c ommissural input to CA1 pyramidal neurons, Cr-/- mice showed no altera tion in basal synaptic transmission, but long-term potentiation (LTP) was impaired in the dentate gyrus. Normal LTP could be restored in the presence of the GABA(A) receptor antagonist bicuculline, suggesting t hat in Cr-/- dentate gyrus an excess of gamma-aminobutyric acid (GABA) release interferes with LTP induction, Synaptic transmission and LTP were normal in CA1 area, which contains only few Cr-positive GABAergic interneurons, Cr-/- mice performed normally in spatial memory task. T hese results suggest that expression of Cr contributes to the control of synaptic plasticity in mouse dentate gyrus by indirectly regulating the activity of GABAergic interneurons, and that Cr-/- mice represent a useful tool to understand the role of dentate LTP in learning and m emory.