Glutamatergic synaptic responses and long-term potentiation are impaired in the CA1 hippocampal area of calbindin D28k-deficient mice

Abstract

The contribution of the cytosolic calcium binding protein calbindin D(28K) (CaBP) to glutamatergic neurotransmission and synaptic plasticity was investigated in hippocampal CA1 area of wild-type and antisense transgenic CaBP-deficient mice, with the use of extracellular recordings in the ex vivo slice preparation. The amplitude of non-N-methyl-D-aspartate receptor (non-NMDAr)-mediated extracellular field excitatory postsynaptic potentials (fEPSPs) recorded in control medium was significantly greater in CaBP-deficient mice, whereas the afferent fiber volley was not affected. In contrast, the amplitude of NMDAr-mediated fEPSPs isolated in a magnesium-free medium after blockade 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 and time course of the short-term potentiation (STP) of fEPSPs induced by a 30 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 stimulation (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 mechanisms responsible for the maintenance of long-term synaptic potentiation, at least in part by modulating the activation of NMDA receptors.

Ontogeny of calbindin immunoreactivity in the human hippocampal formation with a special emphasis on granule cells of the dentate gyrus

“…In addition to other studies, our previous results showed that the maturity of mossy fibers in the rat, revealed with immunohistochemistry against a calcium‐binding protein, calbindin D‐28K (CB), correlates well with the functional maturation of the hippocampal formation (Baimbridge and Miller, 1982; Nadel and Willner, 1989; Sloviter, 1989; Celio, 1990; Ábrahám et al, 2007a). This correlation supports the suggested neuromodulatory role of CB, which was established using transgenic animals with reduced CB expression (Molinari et al, 1996; Jouvenceau et al, 1999). These mice show selective impairments in spatial learning paradigms, and fail to maintain long‐term potentiation, indicating that CB is necessary for LTP, synaptic plasticity and memory functions.…”

Expression of 5-HT7 receptor mRNA in the hamster brain: Effect of aging and association with calbindin-D28K expression

“…It is interesting to note that immunohistochemical studies have shown that another serotonin receptor subtype, the 5-HT 1A receptor, is co-localized with calbindin in several rat brain regions, including the hippocampus, the thalamus and the septum (Aznar et al, 2003). As well as modulating photic phase shifts (Hamada et al, 2003), as described above, calbindin has been implicated in several other functions, including spatial memory, long-term potentiation in the hippocampus, synaptic plasticity, and either neuroprotection or enhanced vulnerability to neurodegeneration (Jouvenceau et al, 1999;Chard et al, 1995;Molinari et al, 1996;Nagerl et al, 2000). Some of these functions, such as memory, long-term potentiation, and synaptic plasticity are also modulated by 5-HT 7 receptors (Perez-Garcia et al, 2006;PerezGarcia and Meneses, 2005;Roberts et al, 2004;Kvachnina et al, 2005).…”

Presenilin-1 mutation impairs cholinergic modulation of synaptic plasticity and suppresses NMDA currents in hippocampus slices

“…Consistent with a loss-offunction mechanism, cells lacking PS1 exhibit impaired Ca 2+ responses to glutamate (Yang and Cook, 2004). Considerable evidence suggests that there is an optimal level of postsynaptic Ca 2+ elevation required for LTP and memory, and that a further increase in the Ca 2+ level can impair LTP and memory ( (Jouvenceau et al, 1999;Price et al, 1999;Tonkikh et al, 2006). Excessive Ca 2+ release in response to muscarinic receptor activation could explain the impairment of LTP caused by carbachol and PT in neurons expressing mutant PS1.…”