LONG-TERM POTENTIATION AND N-METHYL-D-ASPARTATE RECEPTORS IN THE VISUAL-CORTEX OF YOUNG-RATS

LONG-TERM POTENTIATION AND N-METHYL-D-ASPARTATE RECEPTORS IN THE VISUAL-CORTEX OF YOUNG-RATS
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DOI:
10.1113/jphysiol.1989.sp017680
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发表时间:
1989-07-01
影响因子:
5.5
通讯作者:
TSUMOTO, T
TSUMOTO, T
中科院分区:
医学1区
文献类型:
--
作者:
KIMURA, F;NISHIGORI, A;TSUMOTO, T

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1.用记录21~40日龄幼鼠视皮层脑片II/III层细胞外突触电位的方法,研究了强直刺激白色物质后突触传递的长时程增强(LTP)。2.以0.1 Hz的频率对白色物质进行单次电击,作为测试刺激,引起由初级和次级分量组成的场电位。从灌流液中去除Ca2+离子,可以识别出次级成分为突触后起源,初级成分为反映逆向和突触后电位的混合物。3.以5 Hz频率刺激白色物质60 s,观察破伤风后20 min~9 h的场电位。LTP被定义为存在时,反应显示超过20%的增加幅度的Ca 2 +-敏感的组件20分钟后破伤风。在23个切片中的12个切片中诱导了LTP,并且这种增强作用在整个观察期间持续。增强的平均幅度为147.8.+-。12个切片的对照值的28.4%。4.给药的D,L-2-氨基-5-膦酰基戊酸(APV),N-甲基-D-天冬氨酸(NMDA)-偏好受体的选择性拮抗剂,稍微降低场电位的Ca 2+敏感成分的幅度。平均减少幅度为80.2 ±。药物前对照值的15.3%。在APV的存在下,LTP仅在12个测试切片中的一个切片中诱导。5.从第II/III层的23个细胞中获得稳定的细胞内记录。刺激白色物质诱发的兴奋性突触后电位(EPSP)的平均起始时间和峰值潜伏期分别为4.1和11.3 ms。在某些细胞中,这些快速的EPSP之后是另一个慢的EPSP,具有更长的潜伏期和更高的振幅。APV的应用进一步揭示了快速EPSP由两个成分组成,即早期和晚期成分。6.白色物质的Tetanization在12个测试细胞中的8个中诱导了EPSP的持久增强。在这8个细胞中的5个中,快EPSP的幅度增强,在其余3个细胞中,慢EPSP在破伤风后重新出现。7. APV降低快EPSP的振幅,如果存在,则消除慢EPSP。快速EPSP的平均减少幅度为65.6 ±。15.1%,这一减少主要是由于消除了后期部分。该成分具有异常的电压依赖性:即去极化增强和超极化减少。然而,在不含Mg 2+的介质中,这种电压关系变得相反和常规。这些结果被认为是证据的建议,晚成分是通过NMDA受体介导的。8.在存在APV的情况下,强直刺激未能在所有测试的细胞中诱导EPSP的显著增强,但有一个(n = 11)。提示发育中大鼠视皮质LTP的诱导过程中,NMDA受体的激活起着关键作用。
1. Long-term potentiation (LTP) of synaptic transmission following tetanic stimulation of the white matter was studied by recording extracellular synaptic potentials from layer II/III of visual cortical slices from young rats ranging in age from 21 to 40 days. 2. Single shocks applied to the white matter at 0.1 Hz, used as test stimuli, elicited field potentials that consisted of primary and secondary components. The removal of Ca2+ ions from the perfusate allowed identification of the secondary component as originating postsynaptically and the primary one as reflecting a mixture of antidromic and postsynaptic potentials. 3. Tetranic stimulation at 5 Hz for 60 s was delivered to the white matter and field potentials were observed for 20 min to 9 h after the tetanus. LTP was defined as being present when the response displayed more than a 20% increase in amplitude of the Ca2+-sensitive components 20 min after the tetanus. LTP was induced in twelve of twenty-three slices tested, and this potentiation lasted throughout the period of observation. The average magnitude of potentiation was 147.8 .+-. 28.4% of the control value for the twelve slices. 4. Administration of D,L-2-amino-5-phosphonovalerate (APV), an antagonist selective for N-methyl-D-aspartate (NMDA)-preferring receptors, slightly reduced the amplitudes of Ca2+-sensitive components of the field potentials. The average magnitude of reduction was 80.2 .+-. 15.3% of the pre-drug control values. In the presence of APV, LTP was induced in only one slice of twelve tested. 5. Stable intracellular recordings were obtained from twenty-three cells from layer II/III. Excitatory postsynaptic potentials (EPSPs) evoked by white matter stimulation had mean onset and peak latencies of 4.1 and 11.3 ms, respectively. In some cells these fast EPSPs were followed by another slow EPSP with a much longer latency and higher amplitude. Administration of APV revealed further that the fast EPSPs consisted of two components, i.e. early and late components. 6. Tetanization of the white matter induced long-lasting enhancement of EPSPs in eight of twelve cells tested. In five of these eight cells, fast EPSPs were enhanced in amplitude and in the remaining three cells, slow EPSPs appeared de novo after the tetanus. 7. APV reduced the amplitudes of the fast EPSPs and abolished the slow EPSPs if present. The average magnitude of reduction for the fast EPSPs was 65.6 .+-. 15.1% and this reduction was due mainly to an elimination of the late component. This component had the anomalous voltage-dependent properties: i.e. an enhancement with depolarization and reduction with hyperpolarization. In Mg2+-free media, however, this voltage relation became reversed and conventional. These results are taken as evidence for the suggestion that the late component is mediated through NMDA receptors. 8. In the presence of APV, tetanic stimulation failed to induce significant potentiation of EPSPs in all cells tested but one (n = 11). It is suggested that the actviation of NMDA receptors plays a crucial role in the induction of LTP in the developing rat visual cortex.