Deficits in memory and motor performance in synaptotagmin IV mutant mice

摘要

Synaptotagmin (Syt) IV is a synaptic vesicle protein. Syt IV expres- sion is induced in the rat hippocampus after systemic kainic acid treatment. To examine the functional role of this protein in vivo, we derived Syt lV null[Syt lv(-/-)] mutant mice. Studies with the rotorod revealed that the Syt IV mutants have impaired motor coordination, a result consistent with constitutive Syt IV expression in the cerebellum. Because Syt IV is thought to modulate synaptic function, we also have examined Syt lV mutant mice in learning and memory tests. Our studies show that the Syt lV mutation disrupts contextual fear conditioning, a learning task sensitive to hippocampal and amygdala lesions. In contrast, cued fear condi- tioning is normal in the Syt lV mutants, suggesting that this mutation did not disrupt amygdala function. Conditioned taste aversion, which also depends on the amygdala. is normal in the Syt IV mutants. Consistent with the idea that the Syt lv mutation preferentially affects hippocampal function. Syt lV mutant mice also display impaired social transmission of food preference. These studies demonstrate that Syt IV is critical for brain function and suggest that the Syt lV mutation affects hippocampal-dependent learning and memory, as well as motor coordination.