Rapl Signaling Prevents L-Type Calcium Channel-Dependent Neurotransmitter Release.

The small GTPase Rapl contributes to fear learning and cortico-amygdala plasticity by inhibiting glutamate release from cortical neu-rons, but mechanisms of this inhibition remain unknown. Conversely, L-type calcium channels (LTCCs) become involved in glutamate release after fear learning and LTP induction. Here, we show that Rapl deletion in mouse primary cortical neurons increases synaptic vesicle exocytosis without altering endocytosis or vesicle pool size in an LTCC-dependent manner. We identify Erkl/2 as the downstream effector of Rapl and show that its inhibition increases plasma membrane expression of LTCCs near presynaptic terminals. We propose that the Rap 1 signaling enables plasticity and fear learning by regulating LTCCs at cortico-amygdala synapses. [ABSTRACT FROM AUTHOR]