Department of Pharmacology, Physiology and Biotechnology, Carney Institute for Brain Science, Brown University, Providence, Rhode Island 02912.
Department of Pharmacology, Physiology and Biotechnology, Carney Institute for Brain Science, Brown University, Providence, Rhode Island 02912
J Neurosci. 2018 Jun 20;38(25):5750-5758. doi: 10.1523/JNEUROSCI.2772-17.2018. Epub 2018 May 25.
Short-term synaptic plasticity contributes to many computations in the brain and allows synapses to keep a finite record of recent activity. Here we have investigated the mechanisms underlying an intriguing form of short-term plasticity termed labile LTP, at hippocampal and PFC synapses in male rats and male and female mice. In the hippocampus, labile LTP is triggered by high-frequency activation of presynaptic axons and is rapidly discharged with further activation of those axons. However, if the synapses are quiescent, they remain potentiated until further presynaptic activation. To distinguish labile LTP from NMDAR-dependent forms of potentiation, we blocked NMDARs in all experiments. Labile LTP was synapse-specific and was accompanied by a decreased paired pulse ratio, consistent with an increased release probability. Presynaptic Ca and protein kinase activation during the tetanus appeared to be required for its initiation. Labile LTP was not reversed by a PKC inhibitor and did not require either RIM1α or synaptotagmin-7, proteins implicated in other forms of presynaptic short-term plasticity. Similar NMDAR-independent potentiation could be elicited at synapses in mPFC. Labile LTP allows for rapid information storage that is erased under controlled circumstances and could have a role in a variety of hippocampal and prefrontal cortical computations related to short-term memory. Changes in synaptic strength are thought to represent information storage relevant to particular nervous system tasks. A single synapse can exhibit multiple overlapping forms of plasticity that shape information transfer from presynaptic to postsynaptic neurons. Here we investigate the mechanisms underlying labile LTP, an NMDAR-independent form of plasticity induced at hippocampal synapses. The potentiation is maintained for long periods as long as the synapses are infrequently active, but with regular activation, the synapses are depotentiated. Similar NMDAR-independent potentiation can also be induced at L2/3-to-L5 synapses in mPFC. Labile LTP requires a rise in presynaptic Ca and protein kinase activation but is unaffected in RIM1α or synaptotagmin-7 mutant mice. Labile LTP may contribute to short-term or working memory in hippocampus and mPFC.
短期突触可塑性有助于大脑中的许多计算，并使突触能够保持对最近活动的有限记录。在这里，我们研究了在雄性大鼠和雄性和雌性小鼠的海马和 PFC 突触中，一种称为不稳定 LTP 的有趣形式的短期可塑性的机制。在海马体中，不稳定 LTP 是由轴突的高频激活触发的，并随着这些轴突的进一步激活而迅速放电。然而，如果突触处于静止状态，它们会保持增强状态，直到进一步的轴突激活。为了将不稳定 LTP 与 NMDA 受体依赖性的增强形式区分开来，我们在所有实验中都阻断了 NMDA 受体。不稳定 LTP 是突触特异性的，并伴随着配对脉冲比的降低，这与释放概率的增加一致。在强直期间，突触前 Ca 和蛋白激酶的激活似乎是其起始所必需的。不稳定 LTP 不能被 PKC 抑制剂逆转，也不需要 RIM1α 或 synaptotagmin-7，这两种蛋白都与其他形式的突触前短期可塑性有关。在 mPFC 中的突触中也可以引发类似的 NMDA 受体非依赖性增强。不稳定 LTP 允许快速存储信息，在受控条件下可以擦除信息，并可能在与短期记忆相关的各种海马体和前额叶皮层计算中发挥作用。突触强度的变化被认为代表与特定神经系统任务相关的信息存储。单个突触可以表现出多种重叠的可塑性形式，这些形式塑造了从突触前神经元到突触后神经元的信息传递。在这里，我们研究了不稳定 LTP 的机制，这是一种在海马体突触中诱导的 NMDA 受体非依赖性可塑性形式。只要突触很少活动，增强就会持续很长时间，但随着定期激活，突触会去增强。在 mPFC 的 L2/3 到 L5 突触中也可以诱导类似的 NMDA 受体非依赖性增强。不稳定 LTP 需要突触前 Ca 增加和蛋白激酶激活，但在 RIM1α 或 synaptotagmin-7 突变小鼠中不受影响。不稳定 LTP 可能有助于海马体和 mPFC 中的短期或工作记忆。
