Acute and chronic interference with BDNF/TrkB-signaling impair LTP selectively at mossy fiber synapses in the CA3 region of mouse hippocampus
Acute and chronic interference with BDNF/TrkB-signaling impair LTP selectively at mossy fiber synapses in the CA3 region of mouse hippocampus
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DOI：
10.1016/j.neuropharm.2013.03.041
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发表时间：
2013-08-01
影响因子：
4.7
通讯作者：
Edelmann, Elke
中科院分区：
文献类型：
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作者：
Schildt, Sandra;Endres, Thomas;Edelmann, Elke
脑源性神经营养因子（BDNF）通过TrkB信号传导至关重要地调节脑中的突触可塑性。虽然BDNF在海马苔藓纤维（MF）突触中含量丰富，但其在MF突触可塑性（长时程增强，LTP）中的作用仍不清楚。使用场电位记录成年杂合BDNF敲除（ko，BDNF +/-）小鼠的CA3，我们观察到受损的（类似于50%）NMDAR非依赖性MF-LTP。与MF突触相反，LTP在相邻的联合/连合（A/C）纤维突触不受影响。为了排除BDNF +/-小鼠中MF-LTP受损是由于响应于长期降低的BDNF水平的发育变化，并且为了证明BDNF在MF-LTP中的急性可用性的重要性，我们还测试了对BDNF/TrkB信号传导的急性干扰的影响。用k252a或用选择性BDNF清除剂TrkB-Fc抑制TrkB酪氨酸激酶信号传导均抑制MF-LTP至与在BDNF +/-小鼠中观察到的相同程度。基础突触传递，短期可塑性，和突触疲劳在LTP诱导没有显着改变治疗与k252a或TrkB-Fc，或慢性BDNF减少BDNF +/-小鼠。由于对BDNF信号的急性干扰并没有完全阻断MF-LTP，我们的结果提供了证据，证明除了BDNF诱导的TrkB信号外，还有一种额外的机制有助于这种类型的LTP。我们的研究结果首次证明了急性BDNF/TrkB信号传导在成年海马中MF-LTP突触前表达中的机制作用。(C)2013爱思唯尔有限公司保留所有权利。
Brain-derived neurotrophic factor (BDNF) signaling via TrkB crucially regulates synaptic plasticity in the brain. Although BDNF is abundant at hippocampal mossy fiber (MF) synapses, which critically contribute to hippocampus dependent memory, its role in MF synaptic plasticity (long-term potentiation, LTP) remained largely unclear. Using field potential recordings in CA3 of adult heterozygous BDNF knockout (ko, BDNF+/-) mice we observed impaired (similar to 50%) NMDAR-independent MF-LTP. In contrast to MF synapses, LTP at neighboring associative/commissural (A/C) fiber synapses remained unaffected. To exclude that impaired MF-LTP in BDNF+/- mice was due to developmental changes in response to chronically reduced BDNF levels, and to prove the importance of acute availability of BDNF in MF-LTP, we also tested effects of acute interference with BDNF/TrkB signaling. Inhibition of TrkB tyrosine kinase signaling with k252a, or with the selective BDNF scavenger TrkB-Fc, both inhibited MF-LTP to the same extent as observed in BDNF+/- mice. Basal synaptic transmission, short-term plasticity, and synaptic fatigue during LTP induction were not significantly altered by treatment with k252a or TrkB-Fc, or by chronic BDNF reduction in BDNF+/- mice. Since the acute interference with BDNF-signaling did not completely block MF-LTP, our results provide evidence that an additional mechanism besides BDNF induced TrkB signaling contributes to this type of LTP. Our results prove for the first time a mechanistic action of acute BDNF/TrkB signaling in presynaptic expression of MF-LTP in adult hippocampus. (C) 2013 Elsevier Ltd. All rights reserved.