Moulder Krista L, Jiang Xiaoping, Taylor Amanda A, Olney John W, Mennerick Steven
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Neurosci. 2006 Jun 14;26(24):6618-26. doi: 10.1523/JNEUROSCI.5498-05.2006.
Neurons engage compensatory, homeostatic synaptic changes to maintain their overall firing rate. We examined the induction and expression of a persistent presynaptic adaptation. We explored the effect of mild extracellular potassium elevation to increase hippocampal pyramidal neuron spiking over a physiological range. With several days of mild depolarization, glutamate release adapted, as revealed by an increased mismatch between the number of active, FM1-43-positive, glutamatergic synapses and the total number of synapses defined by vesicular glutamate transporter-1 antibody staining. Surprisingly, the adaptation of glutamate terminals was all-or-none; recycling vesicle pool size at remaining active synapses was not significantly altered by the adaptation. Tetrodotoxin (TTX), but not postsynaptic receptor blockade, reversed depolarization-induced adaptation, and TTX added to normal incubation medium increased the number of active synapses, suggesting that normal spiking activity sustains a steady-state percentage of inactive terminals. Chronic mild depolarization depressed EPSCs and decreased the size of the readily releasable pool of vesicles (RRP). Several hours of 10 Hz electrical stimulation also depressed the RRP size, confirming that spiking alone induces adaptation and that strong stimulation induces more rapid presynaptic adaptation. Despite the importance of RRP alteration to the adaptation, ultrastructural experiments revealed no changes in docked or total synaptic vesicle numbers. Furthermore, alpha-latrotoxin induced vesicle release at adapted synapses, consistent with the idea that adaptation resulted from changes in vesicle priming. These results show that glutamatergic neurotransmission persistently adapts to changes in electrical activity over a wide physiological range.
神经元会进行代偿性的、稳态性的突触变化以维持其总体放电率。我们研究了一种持续性突触前适应的诱导和表达。我们探讨了轻度细胞外钾离子升高在生理范围内增加海马锥体神经元放电的作用。经过几天的轻度去极化后，谷氨酸释放出现了适应性变化，这通过活性的、FM1-43阳性的谷氨酸能突触数量与由囊泡谷氨酸转运体-1抗体染色定义的突触总数之间增加的不匹配得以揭示。令人惊讶的是，谷氨酸能终末的适应是全或无的；剩余活性突触处的循环囊泡池大小并未因适应而发生显著改变。河豚毒素（TTX）而非突触后受体阻断可逆转去极化诱导的适应，并且添加到正常孵育培养基中的TTX增加了活性突触的数量，这表明正常的放电活动维持了一定比例的非活性终末的稳态。慢性轻度去极化会抑制兴奋性突触后电流（EPSCs）并减小囊泡的易释放池（RRP）的大小。10赫兹电刺激数小时也会减小RRP的大小，证实仅放电就能诱导适应，且强刺激会诱导更快的突触前适应。尽管RRP改变对适应很重要，但超微结构实验显示停靠或总的突触囊泡数量没有变化。此外，α-银环蛇毒素可诱导适应突触处的囊泡释放，这与适应是由囊泡引发的变化所致的观点一致。这些结果表明，谷氨酸能神经传递在广泛的生理范围内会持续适应电活动的变化。
