The small GTP-binding protein Rab3A is a Rab family member that is abundant in brain synaptic vesicles. Here we show that mice in which the rab3A gene has been mutated by homologous recombination do not express Rab3A but are viable and fertile. Electrophysiological recordings in hippocampal CA1 pyramidal cells indicate that most of their synaptic parameters are also normal, although synaptic depression after short trains of repetitive stimuli (15-30 stimuli at 14 Hz) is significantly increased. Levels of the Rab3A-binding protein rabphilin are decreased by 70%, but expression of more than 20 other synaptic proteins is unchanged. No compensatory changes were detected in other GTP-binding proteins or in proteins that interact with Rab3. Rab3A thus appears not to be essential for synaptic vesicle exocytosis but to play a role in the recruitment of synaptic vesicles for exocytosis during repetitive stimulation.

Auditory information critical for fear conditioning, a model of emotional learning, is conveyed to the lateral nucleus of the amygdala via two routes: directly from the medial geniculate nucleus and indirectly from the auditory cortex. Here we show in the cortico-amygdala pathway that learned fear occludes electrically induced long-term potentiation (LTP). Quantal analysis of the expression of LTP in this pathway reveals a significant presynaptic component reflected in an increase in probability of transmitter release. Conditioned fear also is accompanied by the enhancement in transmitter release at this cortico-amygdala synapse. These results indicate that the synaptic projections from the auditory cortex to the lateral amygdala are modified during the acquisition and expression of fear to auditory stimulation, thus further strengthening the proposed link between LTP in the auditory pathways to the amygdala and learned fear.

Long-term depression (LTD) is an activity-dependent decrease in synaptic efficacy that together with its counterpart, long-term potentiation, is thought to be an important cellular mechanism for learning and memory in the mammalian brain. The induction of LTD in hippocampal CA1 pyramidal neurons in neonatal rats is shown to depend on postsynaptic calcium ion entry through L-type voltage-gated calcium channels paired with the activation of metabotropic glutamate receptors. Although induced postsynaptically, LTD is due to a long-term decrease in transmitter release from presynaptic terminals. This suggests that LTD is likely to require the production of a retrograde messenger.