Huang Y Y, Kandel E R
Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York, New York, USA.
Learn Mem. 1994 May-Jun;1(1):74-82.
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.
为了研究海马体中长时程增强（LTP）的晚期阶段是如何产生的，我们通过施加各种条件性强直刺激，检查了由此产生的LTP的时间进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，一次高频刺激（100Hz）会产生一种形式的LTP，其持续时间超过1小时但少于3小时（LTP的早期阶段，即E-LTP）。它被钙/钙调蛋白激酶II（钙调蛋白激酶II）抑制剂阻断，但不受cAMP依赖性蛋白激酶[蛋白激酶A（PKA）和蛋白质合成抑制剂茴香霉素]抑制剂的影响，也不会被cAMP激活剂福司可林封闭。相比之下，当使用三次高频刺激时，产生的增强作用持续至少6-10小时。三次刺激诱导的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，并被福司可林封闭。这些结果表明，通过改变条件性强直刺激的次数，可以选择性地募集两种机制上不同的LTP形式，一种短暂的早期成分（E-LTP）和一种更持久的形式（L-LTP）。重复强直刺激会诱导一种PKA和蛋白质合成依赖性的晚期成分，该成分会增加单次强直刺激诱导的增强作用的幅度和持续时间。
