Department of Physiology and Neuroscience, NYU School of Medicine, New York, NY 10016, USA.
J Mol Neurosci. 2013 Jan;49(1):223-30. doi: 10.1007/s12031-012-9848-8. Epub 2012 Jul 8.
Synaptic plasticity in many regions of the central nervous system leads to the continuous adjustment of synaptic strength, which is essential for learning and memory. In this study, we show by visualizing synaptic vesicle release in mouse hippocampal synaptosomes that presynaptic mitochondria and, specifically, their capacities for ATP production are essential determinants of synaptic vesicle exocytosis and its magnitude. Total internal reflection microscopy of FM1-43 loaded hippocampal synaptosomes showed that inhibition of mitochondrial oxidative phosphorylation reduces evoked synaptic release. This reduction was accompanied by a substantial drop in synaptosomal ATP levels. However, cytosolic calcium influx was not affected. Structural characterization of stimulated hippocampal synaptosomes revealed that higher total presynaptic mitochondrial volumes were consistently associated with higher levels of exocytosis. Thus, synaptic vesicle release is linked to the presynaptic ability to regenerate ATP, which itself is a utility of mitochondrial density and activity.
中枢神经系统许多区域的突触可塑性导致突触强度的持续调整，这对于学习和记忆至关重要。在这项研究中，我们通过可视化小鼠海马突触小体中的突触小泡释放来表明，突触前线粒体及其产生 ATP 的能力是突触小泡胞吐及其幅度的重要决定因素。用 FM1-43 负载的海马突触小体的全内反射显微镜显示，抑制线粒体氧化磷酸化会减少诱发的突触释放。这种减少伴随着突触小体 ATP 水平的大幅下降。然而，胞质钙内流不受影响。对受刺激的海马突触小体的结构特征进行分析发现，较高的总突触前线粒体体积与较高的胞吐水平一致。因此，突触小泡的释放与突触前再生 ATP 的能力有关，而这本身又是线粒体密度和活性的一个用途。
