Glutamatergic synaptic responses and long-term potentiation are impaired in the CA1 hippocampal area of calbindin D-28K-deficient mice

The contribution of the cytosolic calcium binding protein calbindin D-28K ( CaBP) to glutamatergic neurotransmission and synaptic plasticity was invest igated in hippocampal CA1 area of wild-type and antisense transgenic CaBP-d eficient mice, with the use of extracellular recordings in the ex vivo slic e preparation. The amplitude of non-N-methyl-D-aspartate receptor (non-NMDA r)-mediated extracellular field excitatory postsynaptic potentials (fEPSPs) recorded in control medium was significantly greater in CaBP-deficient mic e, whereas the afferent fiber volley was not affected. In contrast, the amp litude of NMDAr-mediated fEPSPs isolated in a magnesium-free medium after b lockade of non-NMDAr and GABAergic receptors was significantly depressed in these animals. No alteration in the magnitude of paired-pulse facilitation was found, indicating that the presynaptic calcium mechanisms controlling glutamate release were not altered in CaBP-deficient mice. The magnitude an d time course of the short-term potentiation (STP) of fEPSPs induced by a 3 0 Hz conditioning stimulation, which was blocked by the NMDAr antagonist 2- amino-5-phosphonovalerate acid (2-APV), was not impaired in the transgenic mice, whereas long-term potentiation (LTP) induced by a 100 Hz tetanus was not maintained. The long-term. depression (LTD) induced by low-frequency st imulation (1 Hz, 15 min) in the presence of the GABA antagonist bicuculline was not altered. These results argue for a contribution of CaBP to the mec hanisms responsible for the maintenance of long-term synaptic potentiation, at least in part by modulating the activation of NMDA receptors. (C) 1999 Wiley-Liss, Inc.