Epileptic pilocarpine-treated rats exhibit aberrant hippocampal EPSP-spike potentiation but retain long-term potentiation.
Epileptic pilocarpine-treated rats exhibit aberrant hippocampal EPSP-spike potentiation but retain long-term potentiation.
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DOI：
10.14814/phy2.13490
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发表时间：
2017-11
影响因子：
2.5
通讯作者：
Benveniste M
中科院分区：
文献类型：
--
作者：
Carpenter-Hyland E;Bichler EK;Smith M;Sloviter RS;Benveniste M
海马神经元可塑性与学习、记忆和认知密切相关。除了突触功能和连接的修饰，海马神经元经历可塑性的能力涉及改变非突触兴奋性的能力。这包括改变EPSP产生动作电位的可能性（E-S可塑性）。癫痫是一种常见的神经系统疾病，通常与神经元过度兴奋和认知功能障碍有关。我们在匹鲁卡品诱导癫痫持续状态后3-10周检查了慢性癫痫Sprague-Dawley大鼠的E-S可塑性。采用全细胞电流钳法检测海马脑片CA 1区神经元，以测量Schaffer侧支刺激诱发的EPSP。使用弱的尖峰时间依赖性方案来诱导可塑性，我们在盐水处理的大鼠中发现了强的E-S增强和弱的长时程增强（LTP）。在毛果芸香碱治疗的大鼠中，发现了类似程度的LTP，但ES增强作用降低。此外，E-S增强的程度与两组的LTP程度无关，表明它们独立地促进神经元可塑性。E-S增强也不同于LTP，因为E-S可塑性可以仅由突触后电流注入产生的动作电位诱导。细胞内溶液中的钙螯合剂BAPTA阻断了LTP和E-S增强，揭示了这两个过程的钙依赖性。这些发现表明，LTP和E-S增强具有重叠但不相同的诱导神经元可塑性的机制，可能独立地导致在慢性癫痫状态中观察到的认知障碍。
Hippocampal neuron plasticity is strongly associated with learning, memory, and cognition. In addition to modification of synaptic function and connectivity, the capacity of hippocampal neurons to undergo plasticity involves the ability to change nonsynaptic excitability. This includes altering the probability that EPSPs will generate action potentials (E‐S plasticity). Epilepsy is a prevalent neurological disorder commonly associated with neuronal hyperexcitability and cognitive dysfunction. We examined E‐S plasticity in chronically epileptic Sprague–Dawley rats 3–10 weeks after pilocarpine‐induced status epilepticus. CA1 neurons in hippocampal slices were assayed by whole‐cell current clamp to measure EPSPs evoked by Schaffer collateral stimulation. Using a weak spike‐timing‐dependent protocol to induce plasticity, we found robust E‐S potentiation in conjunction with weak long‐term potentiation (LTP) in saline‐treated rats. In pilocarpine‐treated rats, a similar degree of LTP was found, but E‐S potentiation was reduced. Additionally, the degree of E‐S potentiation was not correlated with the degree of LTP for either group, suggesting that they independently contribute to neuronal plasticity. E‐S potentiation also differed from LTP in that E‐S plasticity could be induced solely from action potentials generated by postsynaptic current injection. The calcium chelating agent BAPTA in the intracellular solution blocked LTP and E‐S potentiation, revealing the calcium dependence of both processes. These findings suggest that LTP and E‐S potentiation have overlapping but nonidentical mechanisms of inducing neuronal plasticity that may independently contribute to cognitive disruptions observed in the chronic epileptic state.