Decrease in calbindin content significantly alters LTP but not NMDA receptor and calcium channel properties.
The contribution of the cytosolic calcium binding protein calbindin D(28K) (CaBP) to the synaptic plasticity was investigated in hippocampal CA1 area of wild-type and antisense transgenic CaBP-deficient mice. We showed that long-term potentiation (LTP) induced by tetanic stimulation in CaBP-deficient mice was impaired. The fundamental biophysical properties of NMDA receptors and their number were not modified in CaBP-deficient mice. We also demonstrated that the physiological properties of calcium channels were identical between genotypes. An insufficient Ca(2+) entry through NMDA receptors or calcium channels, or a decrease in NMDA receptor density are unlikely to explain this impairment of LTP. Interestingly, we showed that the loss of LTP was not prevented by glycine but was restored in the presence of a low concentration of the NMDA receptor antagonist D-APV (5 microM) and of the calcium chelator BAPTA-AM (5 microM). Moreover, we observed a loss of LTP in the wild-type mice when the postsynaptic tetanic-induced [Ca(2+)](i) rise is excessively increased. Conversely, a weaker tetanus stimulation allowed LTP induction and maintenance in CaBP-deficient mice. These results suggest that a higher cytosol [Ca(2+)](i), due to the decrease of CaBP expression may impair LTP induction and maintenance mechanisms without affecting the mechanisms of calcium entry. Thus, CaBP plays a critical role in long term synaptic plasticity by limiting the elevation of calcium rise in the cytosol to some appropriate spatio-temporal pattern.
Jouvenceau
A
A
Neurobiologie de la Croissance et de la Sénescence, INSERM U 549, IFR Broca-Sainte Anne, 2ter rue d'Alésia, 75014, Paris, France.
Potier
B
B
Poindessous-Jazat
F
F
Dutar
P
P
Slama
A
A
Epelbaum
J
J
Billard
J-M
JM
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D064026:Calbindins; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D064030:S100 Calcium Binding Protein G / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D064026:Calbindins; D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D064030:S100 Calcium Binding Protein G