Hippocalcin-deficient mice display a defect in cAMP response element-binding protein activation associated with impaired spatial and associative memory

摘要: Abstract Hippocalcin is a member of the neuronal calcium sensor (NCS) protein family that highly expressed in hippocampal pyramidal cells and moderately neurons cerebral cortex, cerebellum striatum. Here we examined physiological roles hippocalcin using targeted gene disruption. Hippocalcin-deficient (−/−) mice displayed no obvious structural abnormalities brain including formation at light microscopic level. Deletion did not result up-regulation hippocalcin-related proteins; neural visinin-like Ca 2+ -binding proteins (NVP) 1, 2, 3. The synaptic excitability CA1 appeared to be normal, as estimated by shape field excitatory postsynaptic potentials elicited single- paired-pulse stimuli, tetanic stimulation. However, N -methyl- d -aspartate stimulation- depolarization-induced phosphorylation cAMP-response element-binding (CREB) was significantly attenuated −/− neurons, suggesting an impairment activity-dependent expression cascade. In Morris water maze test, performance comparable wild-type littermates except probe where crossed previous location platform less often than +/+ mice. were also impaired on discrimination learning task which they needed respond lamp illuminated left or right side obtain food reinforcement. No observed motor activity, anxiety behavior, fear learning. These results suggest plays crucial role -signaling pathway underlies long-lasting plasticity leads spatial associative memory.