Contextual learning induces an increase in the number of hippocampal CA1 neurons expressing high levels of BDNF

Contextual learning induces an increase in the number of hippocampal CA1 neurons expressing high levels of BDNF
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DOI:
10.1016/j.nlm.2007.07.009
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发表时间:
2007-11-01
影响因子:
2.7
通讯作者:
Yamada, Maki K.
Yamada, Maki K.
中科院分区:
心理学4区
文献类型:
--
作者:
Chen, Jenru;Kitanishi, Takuma;Yamada, Maki K.

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我们研究了行为诱导的海马CA 1区脑源性神经营养因子(BDNF)的表达。Sprague-Dawley大鼠在情境恐惧条件反射(CFC)任务中进行训练,4 h后处死,并对其大脑进行免疫组织化学处理。我们发现,在一个小数目(类似于1%)的CA 1神经元在未经训练的动物的BDNF免疫反应性显着高水平。这些特殊的神经元,在本研究中被鉴定为BDNF(++),在CFC后增加了约3%。这种增加在存在记忆损害剂量的NMDA受体拮抗剂(MK 801 0.3mg/kg,i. p.)训练前30分钟。BDNF(++)神经元中的BDNF信号强度与周围的谷氨酸脱羧酶(GAD)65的信号强度相关。GAD 65和BDNF信号强度之间的这种相关性表明,BDNF上调与通过抑制性GABA能突触增加的信号传导相关,这将进一步减少干预神经元的活动。我们的观察,上调BDNF表达的神经元的学习经验后,丰富的GAD 65富集传入突触表明,这些神经元可能有不同的作用,在记忆巩固。(C)2007年爱思唯尔公司All rights reserved.
We examined behaviorally induced expression of brain-derived neurotrophic factor (BDNF) in area CA1 of the hippocampus. Sprague-Dawley rats were trained in a contextual fear conditioning (CFC) task, sacrificed 4 h later, and their brains were processed for immunohistochemistry. We found distinctively high levels of BDNF immunoreactivity in a small number (similar to 1%) of CA1 neurons in untrained animals. The number of these exceptional neurons, which are identified as BDNF(++) in this study, was increased by up to similar to 3% after CFC. This increase was blocked in the presence of a memory-impairing dose of a NMDA receptor antagonist (MK801 0.3 mg/kg, i.p.) given 30 min prior to training. The BDNF signal intensity in BDNF(++) neurons correlated with that of surrounding glutamic acid decarboxylase (GAD) 65. This correlation between GAD65 and BDNF signal intensities suggests that BDNF upregulation was associated with increased signaling via inhibitory GABAergic synapses that would lessen further intervening neuronal activity. Our observation that neurons which upregulate BDNF expression following a learning experience are rich in GAD65-enriched afferent synapses suggests that these neurons may have distinct roles in memory consolidation. (C) 2007 Elsevier Inc. All rights reserved.