Aging differentially alters forms of long-term potentiation in rat hippocampal area CA1
Aging differentially alters forms of long-term potentiation in rat hippocampal area CA1
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DOI：
10.1152/jn.1998.79.1.334
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发表时间：
1998-01-01
影响因子：
2.5
通讯作者：
Robbins, N
中科院分区：
文献类型：
--
作者：
Shankar, S;Teyler, TJ;Robbins, N
衰老对大鼠海马区长时程增强形式的不同影响。J.神经生理素。79：334-341,1998。海马区Schaffer侧支/连合传入的长时程增强(LTP)包括N-甲基-D-天冬氨酸受体(NMDAR)和电压依赖性钙通道(VDCC)两种依赖形式。本研究以青年(2mo)和老年(24mo)Fischer 344大鼠为研究对象，研究了这两种形式的LTP在体外培养的大鼠海马脑片中的相对作用。用细胞外记录方法记录了4列200-Hz0.5-S强直刺激前后的兴奋性突触后电位，其中S各5列。在对照条件下，在幼年和老年动物中均可诱导出由两种形式组成的复合LTP，并且在时间进程和大小上都相似。应用10 mU M硝苯地平(一种电压依赖性钙通道阻滞剂)分离的NMDAR依赖性LTP(NmdaLTP)在老年动物中的幅度显著降低。在老年动物中，应用L-2-氨基-5-磷酸戊酸(APV)分离的VDCC依赖形式(VdccLTP)显著大于老年动物。虽然幼年动物在破伤风后40-60分钟这两种LTP形式均达到稳定值，但老年动物在此期间vdccLTP增加，nmdaLTP减少。在幼年和老年动物中，这两种分离的LTP形式的总和接近于复合LTP的大小，APV和硝苯地平或Genstein(一种酪氨酸激酶抑制剂)的应用共同阻断了增强作用。这些结果表明，衰老导致突触可塑性从依赖NMDAR的机制转变为依赖VDCC的机制。这些数据与前人关于老年CA1细胞L型钙电流增加和NMDAR数量减少的发现一致，并可能有助于解释与年龄相关的学习记忆障碍。
Aging differentially alters forms of long-term potentiation in rat hippocampal area CAl. J. Neurophysiol. 79: 334-341, 1998. Long-term potentiation (LTP) of the Schaffer collateral/commissural inputs to CAI in the hippocampus was shown to consist of N-methyl-D-aspartate receptor (NMDAR) and voltage-dependent calcium channel (VDCC) dependent forms. In this study, the relative contributions of these two forms of LTP in in vitro hippocampal slices from young (2 mo) and old (24 mo) Fischer 344 rats were examined. Excitatory postsynaptic potentials (EPSP) were recorded extracellularly from stratum radiat-um before and after II tetanic stimulus consisting of four 200-Hz, 0.5-s trains given 5 s apart. Under control conditions, a compound LTP consisting of both forms was induced and was similar, in both time course and magnitude, in young and old animals. NMDAR-dependent LTP (nmdaLTP), isolated by the application of 10 mu M nifedipine (a voltage-dependent calcium channel blocker), was significantly reduced in magnitude in aged animals. The VDCC dependent form (vdccLTP), isolated by the application of 50 mu M D,L-2-amino-5-phosphonvalerate (APV), was significantly larger in aged animals. Although both LTP forms reached stable values 40-60 min posttetanus in young animals, in aged animals vdccLTP increased and nmdaLTP decreased during this time. In both young and old animals, the sum of the two isolated LTP forms approximated the magnitude of the compound LTP, and application of APV and nifedipine or genestein (a tyrosine kinase inhibitor) together blocked potentiation. These results suggest that aging causes a shift in synaptic plasticity from NMDAR-dependent mechanisms to VDCC-dependent mechanisms. The data are consistent with previous findings of increased L-type calcium current and decreased NMDAR number In aged CAI cells and may help explain age-related deficits in learning and memory.