RAB3A IS ESSENTIAL FOR MOSSY FIBER LONG-TERM POTENTIATION IN THE HIPPOCAMPUS

Repetitive activation of excitatory synapses in the central nervous sy stem results in a long-lasting increase in synaptic transmission calle d long-term potentiation (LTP). It is generally believed that this syn aptic plasticity may underlie certain forms of learning and memory. LT P at most synapses involves the activation of the NMDA (N-methyl-D-asp artate) subtype of glutamate receptor, but LTP at hippocampal messy fi bre synapses is independent of NMDA receptors and has a component that is induced and expressed presynaptically(1). It appears to be trigger ed by a rise in presynaptic Ca2+ (refs 2, 3), and requires the activat ion of protein kinase A(4-6), which leads to an increased release of g lutamate(3,7-10). A great deal is known about the biochemical steps in volved in the vesicular release of transmitter(11-13), but none of the se steps has been directly implicated in long-term synaptic plasticity . Here we show that, although a variety of short-term plasticities are normal, LTP at messy fibre synapses is abolished in mice lacking the synaptic vesicle protein Rab3A.