Estrous Cycle-Dependent Phasic Changes in the Stoichiometry of Hippocampal Synaptic AMPA Receptors in Rats.

Estrous Cycle-Dependent Phasic Changes in the Stoichiometry of Hippocampal Synaptic AMPA Receptors in Rats.
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DOI:
10.1371/journal.pone.0131359
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Takahashi T
Takahashi T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tada H;Koide M;Ara W;Shibata Y;Funabashi T;Suyama K;Goto T;Takahashi T

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认知功能会受到发情周期的影响。然而,发情周期对突触功能的影响还知之甚少。在这里,我们证明了在雌性大鼠中,抑制-避免(IA)任务(依赖于海马体的情景恐惧学习任务)在发情周期的所有时期都将缺乏钙离子通透性的AMPA受体(CP-AMPAR)驱动到海马CA3-CA1突触中,除了发情期,此时雌激素水平很高。此外,IA任务只有在雌激素存在的情况下才能将CP-AMPAR驱动到去卵巢大鼠的CA3-CA1突触中。因此,学习过程中AMPA受体化学计量的变化取决于雌激素水平。此外,在发情前期,IA任务后长时程增强(LTP)的诱导被阻止,而在发情周期的其他时期,IA任务后仍有完整的LTP表达。与这一发现一致的是,在发情期,接受IA训练的大鼠未能获得依赖海马体的Y迷宫任务。另一方面,在其他发情期,大鼠在IA条件反射后能够学习Y迷宫任务。这些结果表明,高雌激素水平阻止了IA学习诱导的CP-AMPAR传递到海马CA3-CA1突触,并限制了IA任务后突触的可塑性,从而阻止了额外学习的获得。
Cognitive function can be affected by the estrous cycle. However, the effect of the estrous cycle on synaptic functions is poorly understood. Here we show that in female rats, inhibitory-avoidance (IA) task (hippocampus-dependent contextual fear-learning task) drives GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs) into the hippocampal CA3-CA1 synapses during all periods of the estrous cycle except the proestrous period, when estrogen levels are high. In addition, IA task failed to drive CP-AMPARs into the CA3-CA1 synapses of ovariectomized rats only when estrogen was present. Thus, changes in the stoichiometry of AMPA receptors during learning depend on estrogen levels. Furthermore, the induction of long-term potentiation (LTP) after IA task was prevented during the proestrous period, while intact LTP is still expressed after IA task during other period of the estrous cycle. Consistent with this finding, rats conditioned by IA training failed to acquire hippocampus-dependent Y-maze task during the proestrous period. On the other hand, during other estrous period, rats were able to learn Y-maze task after IA conditioning. These results suggest that high estrogen levels prevent the IA learning-induced delivery of CP-AMPARs into hippocampal CA3-CA1 synapses and limit synaptic plasticity after IA task, thus preventing the acquisition of additional learning.
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