The active zone protein RIM1α is required both for maintaining normal probability of neurotransmitter release and for long-term presynaptic potentiation at brain synapses. We now demonstrate that RIM1α -/- mice exhibit normal coordination and anxiety-related behaviors but display severely impaired learning and memory. Mice with a synaptotagmin 1 mutation, which selectively lowers release probability, and mice with Rab3A deletion, which selectively abolishes presynaptic long-term potentiation, do not exhibit this abnormality. Our data suggest that a decrease in release probability or a loss of presynaptic LTP alone is not sufficient to cause major behavioral alterations, but the combination of presynaptic abnormalities in RIM1α-/- mice severely alters learning and memory.
ASJC Scopus subject areas