Lu Hui-Chen, Butts Daniel A, Kaeser Pascal S, She Wei-Chi, Janz Roger, Crair Michael C
Department of Neuroscience, Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
J Neurosci. 2006 Mar 8;26(10):2692-703. doi: 10.1523/JNEUROSCI.3956-05.2006.
Cortical maps are remarkably precise, with organized arrays of thalamocortical afferents (TCAs) that project into distinct neuronal modules. Here, we present evidence for the involvement of efficient neurotransmitter release in mouse cortical barrel map development using barrelless mice, a loss-of-function mutant of calcium/calmodulin-activated adenylyl cyclase I (AC1), and mice with a mutation in Rab3-interacting molecule 1alpha (RIM1alpha), an active zone protein that regulates neurotransmitter release. We demonstrate that release efficacy is substantially decreased in barrelless TCAs. We identify RIMs as important phosphorylation targets for AC1 in the presynaptic terminal. We further show that RIM1alpha mutant mice have reduced TCA neurotransmitter release efficacy and barrel map deficits, although not as severe as those found in barrelless mice. This supports the role of RIM proteins in mediating, in part, AC1 signaling in barrel map development. Finally, we present a model to show how inadequacies in presynaptic function can interfere with activity-dependent processes in neuronal circuit formation. These results demonstrate how efficient synaptic transmission mediated by AC1 function contributes to the development of cortical barrel maps.
皮质图谱非常精确，具有有组织排列的丘脑皮质传入纤维（TCA），这些纤维投射到不同的神经元模块中。在此，我们利用无桶小鼠（一种钙/钙调蛋白激活的腺苷酸环化酶I（AC1）功能缺失突变体）以及Rab3相互作用分子1α（RIM1α）发生突变的小鼠（RIM1α是一种调节神经递质释放的活性区蛋白），提供了有效神经递质释放参与小鼠皮质桶状图谱发育的证据。我们证明，在无桶TCA中释放效率显著降低。我们确定RIMs是突触前终末中AC1的重要磷酸化靶点。我们进一步表明，RIM1α突变小鼠的TCA神经递质释放效率降低且桶状图谱存在缺陷，尽管不如在无桶小鼠中发现得那么严重。这支持了RIM蛋白在部分介导桶状图谱发育中的AC1信号传导中的作用。最后，我们提出了一个模型，以展示突触前功能不足如何干扰神经元回路形成中依赖活动的过程。这些结果证明了由AC1功能介导的有效突触传递如何促进皮质桶状图谱的发育。
