Doc2α 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 generated homozygous null Doc2 alpha mutant mice. In the CA1 region of hippocampal slices in the mutant mice, excitatory synaptic responses evoked with prolonged 5 Hz stimulation showed a significantly larger frequency facilitation followed by a steeper depression than those in wild-type mice, whereas there was no difference in synaptic transmission at lower frequencies or in paired-pulse facilitation. These results suggest that Doc2 alpha regulates synaptic 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 transmitter release during repetitive synaptic activation, thereby contributing to memory formation.