Unit on Behavioral Genetics, Laboratory of Molecular Pathophysiology, National Institute of Mental Health and Microscopy and Imaging Core, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Neurosci. 2013 Apr 24;33(17):7245-52. doi: 10.1523/JNEUROSCI.5963-11.2013.
The small GTPase Rap1 contributes to fear learning and cortico-amygdala plasticity by inhibiting glutamate release from cortical neurons, 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 Rap1 deletion in mouse primary cortical neurons increases synaptic vesicle exocytosis without altering endocytosis or vesicle pool size in an LTCC-dependent manner. We identify Erk1/2 as the downstream effector of Rap1 and show that its inhibition increases plasma membrane expression of LTCCs near presynaptic terminals. We propose that the Rap1 signaling enables plasticity and fear learning by regulating LTCCs at cortico-amygdala synapses.
小分子 GTP 酶 Rap1 通过抑制皮质神经元释放谷氨酸来促进恐惧学习和皮质-杏仁核可塑性，但这种抑制的机制尚不清楚。相反，L 型钙通道 (LTCC) 在恐惧学习和 LTP 诱导后参与谷氨酸的释放。在这里，我们发现，在小鼠原代皮质神经元中敲除 Rap1 以 LTCC 依赖性的方式增加突触囊泡胞吐作用，而不改变内吞或囊泡库大小。我们确定 Erk1/2 是 Rap1 的下游效应物，并表明其抑制作用增加了 LTCC 在突触前末梢附近的质膜表达。我们提出，Rap1 信号通过调节皮质-杏仁核突触处的 LTCC 来实现可塑性和恐惧学习。
