Learning induces neurotrophin signaling at hippocampal synapses
Learning induces neurotrophin signaling at hippocampal synapses
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DOI：
10.1073/pnas.0912973107
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发表时间：
2010-04-13
影响因子：
11.1
通讯作者：
Gall, Christine M.
中科院分区：
文献类型：
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作者：
Chen, Lulu Y.;Rex, Christopher S.;Gall, Christine M.
学习诱导的营养活动被认为是维持衰老大脑健康的关键。我们在这里报告说，学习，通过一个意想不到的途径，激活突触受体的大脑的主要营养因子之一。无监督的学习，但不是单独的探索活动，强烈增加了与激活（磷酸化）形式的BDNF的TrkB受体在成年大鼠海马突触后密度的数量，这些增加被阻断的NMDA受体拮抗剂。类似地，在学习相关的θ频率下刺激海马切片以NMDA受体依赖的方式增加突触TrkB磷酸化。Theta爆发刺激，这是更有效的，在这方面比其他刺激模式，优先从事NMDA受体，反过来，激活Src激酶。阻断后者，或清除细胞外TrkB配体，阻止θ诱导的TrkB磷酸化。因此，突触TrkB激活依赖于配体呈递和突触后信号级联。这些结果表明，参与记忆编码的传入活动模式和细胞事件通过突触TrkB启动BDNF信号传导，从而确保学习将触发神经营养支持。
Learning-induced trophic activity is thought to be critical for maintaining health of the aging brain. We report here that learning, acting through an unexpected pathway, activates synaptic receptors for one of the brain's primary trophic factors. Unsupervised learning, but not exploratory activity alone, robustly increased the number of postsynaptic densities associated with activated (phosphorylated) forms of BDNF's TrkB receptor in adult rat hippocampus; these increases were blocked by an NMDA receptor antagonist. Similarly, stimulation of hippocampal slices at the learning-related theta frequency increased synaptic TrkB phosphorylation in an NMDA receptor-dependent fashion. Theta burst stimulation, which was more effective in this regard than other stimulation patterns, preferentially engaged NMDA receptors that, in turn, activated Src kinases. Blocking the latter, or scavenging extracellular TrkB ligands, prevented theta-induced TrkB phosphorylation. Thus, synaptic TrkB activation was dependent upon both ligand presentation and postsynaptic signaling cascades. These results show that afferent activity patterns and cellular events involved in memory encoding initiate BDNF signaling through synaptic TrkB, thereby ensuring that learning will trigger neurotrophic support.