Zakharenko Stanislav S, Patterson Susan L, Dragatsis Ioannis, Zeitlin Scott O, Siegelbaum Steven A, Kandel Eric R, Morozov Alexei
Center for Neurobiology and Behavior, Columbia University, 722 West 168th Street, New York, NY 10032, USA.
Neuron. 2003 Sep 11;39(6):975-90. doi: 10.1016/s0896-6273(03)00543-9.
Brain-derived neurotrophic factor (BDNF) has been implicated in several forms of long-term potentiation (LTP) at different hippocampal synapses. Using two-photon imaging of FM 1-43, a fluorescent marker of synaptic vesicle cycling, we find that BDNF is selectively required for those forms of LTP at Schaffer collateral synapses that recruit a presynaptic component of expression. BDNF-dependent forms of LTP also require activation of L-type voltage-gated calcium channels. One form of LTP with presynaptic expression, theta burst LTP, is thought to be of particular behavioral importance. Using restricted genetic deletion to selectively disrupt BDNF production in either the entire forebrain (CA3 and CA1) or in only the postsynaptic CA1 neuron, we localize the source of BDNF required for LTP to presynaptic neurons. These results suggest that long-term synaptic plasticity has distinct presynaptic and postsynaptic modules. Release of BDNF from CA3 neurons is required to recruit the presynaptic, but not postsynaptic, module of plasticity.
脑源性神经营养因子(BDNF)与不同海马突触处的多种长时程增强(LTP)形式有关。利用FM 1-43(一种突触囊泡循环的荧光标记物)的双光子成像技术,我们发现,在那些募集表达的突触前成分的谢弗侧支突触处的LTP形式中,BDNF是选择性必需的。BDNF依赖的LTP形式也需要L型电压门控钙通道的激活。一种具有突触前表达的LTP形式,即theta爆发LTP,被认为具有特别重要的行为学意义。利用限制性基因缺失技术选择性地破坏整个前脑(CA3和CA1)或仅突触后CA1神经元中的BDNF产生,我们将LTP所需的BDNF来源定位到突触前神经元。这些结果表明,长期突触可塑性具有不同的突触前和突触后模块。需要从CA3神经元释放BDNF来募集可塑性的突触前而非突触后模块。