Morgan S L, Teyler T J
Department of Neurobiology and Pharmacology, Northeastern Ohio Universities College of Medicine, 4209 State Rt. 44, Rootstown, OH 44272-0095, USA.
J Neurophysiol. 2001 Sep;86(3):1289-96. doi: 10.1152/jn.2001.86.3.1289.
The induction of long-term potentiation (LTP) by high-frequency stimulation is considered an acceptable model for the study of learning and memory. In area CA1 calcium influx through N-methyl-D-aspartate receptors (NMDARs; nmdaLTP) and/or L-type voltage-dependent calcium channels (vdccLTP) results in distinct forms of LTP. In the light of significant accumulation of knowledge about patterns of naturally occurring activity in the intact animal, we examined whether the application of stimuli patterned after natural activity induced nmdaLTP and/or vdccLTP. In rat hippocampal slices we examined LTP induced by three types of patterned stimulation short (S-TBS), long (L-TBS), and high-intensity long theta-patterned stimulation (HL-TBS). The patterns of stimulation were applied in control, nifedipine (blocks vdccLTP), D,L-2-amino-5-phosphonovaleric acid (APV; blocks nmdaLTP), or APV and nifedipine containing media. We found that S-TBS resulted in LTP that was completely attenuated in the presence of APV but was unaffected by nifedipine. Thus S-TBS results in the selective induction of nmdaLTP. L-TBS resulted in LTP that was completely blocked by APV and only partially blocked by nifedipine. Therefore L-TBS results in a compoundLTP consisting of both nmdaLTP and vdccLTP components. In the presence of APV, HL-TBS resulted in vdccLTP, and when APV and nifedipine were both present, LTP was completely blocked. Thus HL-TBS results in a vdccLTP in isolation when APV is present. We also examined saturation of S-TBS-induced LTP (nmdaLTP) by applying S-TBS at short intervals. When nifedipine was present, multiple S-TBS trains resulted in a substantially smaller final LTP as compared with controls. We conclude that multiple bursts of S-TBS eventually summate to result in compoundLTP. Stimuli patterned after innate rhythms in the hippocampus effectively induce nmdaLTP (S-TBS), compoundLTP (L-TBS), or vdccLTP (HL-TBS).
高频刺激诱导的长时程增强 (LTP) 被认为是学习和记忆研究的一个可接受模型。在CA1区，通过N-甲基-D-天冬氨酸受体 (NMDARs；nmdaLTP) 和/或L型电压依赖性钙通道 (vdccLTP) 的钙内流导致不同形式的LTP。鉴于在完整动物中关于自然发生活动模式的知识大量积累，我们研究了模仿自然活动模式施加的刺激是否能诱导nmdaLTP和/或vdccLTP。在大鼠海马切片中，我们研究了由三种模式刺激诱导的LTP：短 (S-TBS)、长 (L-TBS) 和高强度长θ模式刺激 (HL-TBS)。刺激模式在对照、硝苯地平 (阻断vdccLTP)、D,L-2-氨基-5-磷酸缬氨酸 (APV；阻断nmdaLTP) 或含APV和硝苯地平的培养基中施加。我们发现，S-TBS诱导的LTP在存在APV时完全减弱，但不受硝苯地平影响。因此，S-TBS导致nmdaLTP的选择性诱导。L-TBS诱导的LTP被APV完全阻断，仅被硝苯地平部分阻断。因此，L-TBS导致由nmdaLTP和vdccLTP成分组成的复合LTP。在存在APV的情况下，HL-TBS导致vdccLTP，当APV和硝苯地平都存在时，LTP被完全阻断。因此，当存在APV时，HL-TBS单独导致vdccLTP。我们还通过短间隔施加S-TBS来研究S-TBS诱导的LTP (nmdaLTP) 的饱和度。当存在硝苯地平时，与对照相比，多个S-TBS序列导致最终LTP显著减小。我们得出结论，多个S-TBS爆发最终总和导致复合LTP。模仿海马先天节律的刺激有效地诱导nmdaLTP (S-TBS)、复合LTP (L-TBS) 或vdccLTP (HL-TBS)。
