Impaired long-term potentiation induction in dentate gyrus of calretinin-deficient mice

Abstract

Calretinin (Cr) is a Ca 2؉ binding protein present in various populations of neurons distributed in the central and peripheral nervous systems. We have generated Cr-deficient (Cr ؊/؊ ) mice by gene targeting and have investigated the associated phenotype. Cr ؊/؊ mice were viable, and a large number of morphological, biochemical, and behavioral parameters were found unaffected. In the normal mouse hippocampus, Cr is expressed in a widely distributed subset of GABAergic interneurons and in hilar mossy cells of the dentate gyrus. Because both types of cells are part of local pathways innervating dentate granule cells and͞or pyramidal neurons, we have explored in Cr ؊/؊ mice the synaptic transmission between the perforant pathway and granule cells and at the Schaffer commissural input to CA1 pyramidal neurons. Cr ؊/؊ mice showed no alteration 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 that in Cr ؊/؊ dentate gyrus an excess of ␥-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. These 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 memory.

Cytosolic Ca2+ Buffers

“…For more details, see Schwaller 2009. CR 2/2 mice show impaired long-term potentiation (LTP) in the hippocampus (Gurden et al 1998;Schurmans et al 1997). While the effect on hippocampal LTP is indirect, the uniform expression of CR in cerebellar granule cells, together with the stereotypic cerebellar organization, has allowed for a detailed investigation of CR in vivo.…”

Perturbed dentate gyrus function in serotonin 5-HT 2C receptor mutant mice

“…In two recent reports, mutant mice lacking the neuronal glycoprotein Thy-1 and the Ca 2ϩ -binding protein calretinin had normal MWM performance despite partial deficits in perforant-path LTP, leading to the suggestion of a dissociation between LTP and MWM performance (41,42). However, these deficits both were demonstrated to result from enhanced GABAergic inhibition in the dentate gyrus of these mutants; when inhibition was blocked by using bicuculline, normal LTP was observed, indicating that the LTP mechanism itself was intact in these animals.…”

Calretinin Interneurons are Early Targets of Extracellular Amyloid-β Pathology in PS1/AβPP Alzheimer Mice Hippocampus

“…Therefore, the aim of the current study was to extend our previous results about interneuron vulnerability in AD by evaluating if calretinin interneurons were also affected in the hippocampal formation of our PS1/AβPP model at early stages of Aβ pathology. This CR-positive GABAergic subpopulation plays a crucial role in the hippocampal activity by controlling other interneurons terminating on different dendritic and somatic compartments of principal cells [18][19][20]. Here, we have quantitatively determined, by immunohistochemistry and stereological approaches, the number of CR immunoreactive interneurons in CA1 and CA2/3 subfields of 2, 4, 6, and 12 month-old PS1/AβPP mice hippocampus compared to wild type (WT) and single transgenic PS1 littermates.…”