Recruitment of long-lasting and protein kinase A-dependent long-term potentiation in the CA1 region of hippocampus requires repeated tetanization.
Recruitment of long-lasting and protein kinase A-dependent long-term potentiation in the CA1 region of hippocampus requires repeated tetanization.
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DOI：
10.1101/lm.1.1.74
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发表时间：
1994-05
影响因子：
2
通讯作者：
Yan-You Huang;E. Kandel
中科院分区：
文献类型：
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作者：
Yan-You Huang;E. Kandel
为了研究海马体长时程增强 (LTP) 的晚期阶段是如何产生的，我们通过应用各种条件破伤风检查了所产生的 LTP 的时间过程及其对蛋白质合成和不同第二信使激酶的依赖性。我们发现，一列高频列车 (100 Hz) 会产生一种持续时间超过 1 小时但不到 3 小时的 LTP（LTP 的早期阶段，或 E-LTP）。它被钙/钙调蛋白激酶 II (Cam 激酶 II) 抑制剂阻断，但不受 cAMP 依赖性蛋白激酶抑制剂 [蛋白激酶 A (PKA) 和蛋白质合成抑制剂茴香霉素] 影响，也不受 cAMP 激活剂毛喉素 (forskolin) 阻断。相比之下，当使用三个高频序列时，所产生的增强作用会持续至少 6-10 小时。三个序列诱导的 L-LTP 与 E-LTP 的不同之处在于，它需要新的蛋白质合成，被 cAMP 依赖性蛋白激酶抑制剂阻断，并被毛喉素 (forskolin) 封闭。这些结果表明，两种机制上不同的 LTP 形式，即短暂的早期成分 (E-LTP) 和更持久的形式 (L-LTP)，可以通过改变条件性强直训练的数量来选择性地招募。重复的破伤风会诱导 PKA 和蛋白质合成依赖性晚期成分，从而增加单次破伤风诱导的增强幅度和持续时间。
To study how the late phase of long-term potentiation (LTP) in hippocampus arises, we examined the resulting LTP for its time course and its dependence on protein synthesis and different second-messenger kinases by applying various conditioning tetani. We find that one high-frequency train (100 Hz) produces a form of LTP that lasts longer than 1 hr but less than 3 hr (the early phase of LTP, or E-LTP). It is blocked by inhibitors of calcium/calmodulin kinase II (Cam kinase II) but is not affected by an inhibitor of cAMP-dependent protein kinase [protein kinase A (PKA) and the protein synthesis inhibitor anisomycin] nor is it occluded by the cAMP activator forskolin. In contrast, when three high-frequency trains are used, the resulting potentiation persists for at least 6-10 hr. The L-LTP induced by three trains differs from the E-LTP in that it requires new protein synthesis, is blocked by an inhibitor of cAMP-dependent protein kinase, and is occluded by forskolin. These results indicate that the two mechanistically distinctive forms of LTP, a transient, early component (E-LTP) and a more enduring form (L-LTP), can be recruited selectively by changing the number of conditioning tetanic trains. Repeated tetani induce a PKA and protein synthesis-dependent late component that adds to the amplitude and duration of the potentiation induced by a single tetanus.