McCann Corey M, Tapia Juan Carlos, Kim Han, Coggan Jay S, Lichtman Jeff W
Department of Molecular & Cellular Biology, Harvard University, 7 Divinity Ave., Cambridge, Massachusetts 02138, USA.
Nat Neurosci. 2008 Jul;11(7):807-15. doi: 10.1038/nn.2145. Epub 2008 Jun 22.
Synaptic plasticity underlies the adaptability of the mammalian brain, but has been difficult to study in living animals. Here we imaged the synapses between pre- and postganglionic neurons in the mouse submandibular ganglion in vivo, focusing on the mechanisms that maintain and regulate neurotransmitter receptor density at postsynaptic sites. Normally, synaptic receptor densities were maintained by rapid exchange of receptors with nonsynaptic regions (over minutes) and by continual turnover of cell surface receptors (over hours). However, after ganglion cell axons were crushed, synaptic receptors showed greater lateral mobility and there was a precipitous decline in insertion. These changes led to near-complete loss of synaptic receptors and synaptic depression. Disappearance of postsynaptic spines and presynaptic terminals followed this acute synaptic depression. Therefore, neurotransmitter receptor dynamism associated with rapid changes in synaptic efficacy precedes long-lasting structural changes in synaptic connectivity.
突触可塑性是哺乳动物大脑适应性的基础,但在活体动物中一直难以研究。在这里,我们对小鼠下颌下神经节中节前和节后神经元之间的突触进行了体内成像,重点关注维持和调节突触后位点神经递质受体密度的机制。正常情况下,突触受体密度通过与非突触区域的受体快速交换(在数分钟内)以及细胞表面受体的持续更新(在数小时内)来维持。然而,在神经节细胞轴突被挤压后,突触受体表现出更大的侧向流动性,插入急剧下降。这些变化导致突触受体几乎完全丧失和突触抑制。突触后棘突和突触前终末的消失发生在这种急性突触抑制之后。因此,与突触效能快速变化相关的神经递质受体动态变化先于突触连接的长期结构变化。