FACTORS REGULATING THE MAGNITUDE OF LONG-TERM POTENTIATION INDUCED BY THETA PATTERN STIMULATION

FACTORS REGULATING THE MAGNITUDE OF LONG-TERM POTENTIATION INDUCED BY THETA PATTERN STIMULATION
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DOI:
10.1016/0006-8993(92)90181-8
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发表时间:
1992-12-11
期刊:
影响因子:
2.9
通讯作者:
LYNCH, G
LYNCH, G
中科院分区:
医学3区
文献类型:
--
作者:
ARAI, A;LYNCH, G

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在海马Theta节律之后模式化的电刺激产生稳健且稳定的长时程增强(LTP)效应。在本研究中使用的药理学操作,在努力相关的特性,在theta刺激的增强的幅度,随后it.Comparisons使用5个或10个脉冲串的刺激,分别诱导次最大或接近最大程度的LTP。DPCPX是一种通过阻断腺苷A1受体来增加释放的药物,用于增强由个体θ爆发产生的去极化。这导致了由5个θ脉冲串引起的稳定LTP的量显著增加,但不影响由10个θ脉冲串引起的稳定LTP的量。这一发现表明,去极化发生在爆发性反应的影响,每爆发增强,但不是最大LTP的上限。阿尼西坦是一种通过作用于谷氨酸(AMPA)受体来增强反应的促智药物,用于验证这一结论。像DPCPX一样,阿尼西坦增加了爆发反应的大小,并增强了由5个而不是10个θ爆发引起的LTP程度。Forskolin是腺苷酸环化酶的激活剂,用于测试阻断通常存在于θ爆发之间的超极化对LTP诱导的影响。该药物增强了5 θ爆发导致的LTP程度,与DPCPX和阿尼西坦相比,几乎是10次爆发的两倍。因此,药物影响每爆发增强和LTP的上限。这些结果进行了讨论的假设,其中的NMDA受体介导的电流的大小影响的程度,由个人θ突发产生的增强,而电流的持续时间是有关的一系列突发引起的最大LTP的限制。研究结果对学习的可能影响也被考虑。
Electrical stimulation patterned after the hippocampal theta rhythm produces a robust and stable long-term potentiation (LTP) effect. Pharmacological manipulations were used in the present studies in an effort to relate characteristics of the responses occurring during theta stimulation to the magnitude of potentiation which follows it. Comparisons were made using five or ten bursts of stimulation which respectively induce sub-maximal or near maximal degrees of LTP. DPCPX, a drug that increases release by blocking adenosine Al receptors, was used to enhance the depolarization produced by individual theta bursts. This resulted in a marked increase in the amount of stable LTP induced by five theta bursts but did not affect that resulting from ten bursts. This finding suggested that depolarization occurring during a burst response influences per burst potentiation but not the ceiling on maximum LTP. Aniracetam, a nootropic drug that enhances responses via an action on glutamate (AMPA) receptors, was used to test this conclusion. Like DPCPX, aniracetam increased the size of the burst response and enhanced the degree of LTP caused by five but not ten theta bursts. Forskolin, an activator of adenylate cyclase, was used to test the effects of blocking the hyperpolarization normally present between theta bursts on the induction of LTP. The drug augmented the degree of LTP resulting from five theta bursts and, in contrast to DPCPX and aniracetam, nearly doubled that obtained with ten bursts. Thus the drug affected both per burst potentiation and the ceiling on LTP. These results are discussed in terms of an hypothesis in which the magnitude of NMDA receptor mediated currents affects the degree of potentiation produced by individual theta bursts while the duration of the currents is related to the limit on the maximum LTP induced by a series of bursts. The possible implications of the findings for learning are also considered.