Doc2 alpha is an activity-dependent modulator of excitatory synaptic transmission

Doc2 alpha is a synaptic vesicle-associated Ca2+-binding protein. To study the role of Doc2 alpha in synaptic transmission and modulation, we generate d homozygous null Doc2 alpha mutant mice. In the CA1 region of hippocampal slices in the mutant mice, excitatory synaptic responses evoked with prolon ged 5 Hz stimulation showed a significantly larger frequency facilitation f ollowed by a steeper depression than those in wild-type mice, whereas there was no difference in synaptic transmission at lower frequencies or in pair ed-pulse facilitation. These results suggest that Doc2 alpha regulates syna ptic transmission when high Ca2+ concentrations in the presynaptic terminal are sustained. Furthermore, the mutant mice showed impairment in long-term potentiation and passive avoidance task. Thus, Doc2 alpha may regulate tra nsmitter release during repetitive synaptic activation, thereby contributin g to memory formation.