EVIDENCE FOR SILENT SYNAPSES - IMPLICATIONS FOR THE EXPRESSION OF LTP

EVIDENCE FOR SILENT SYNAPSES - IMPLICATIONS FOR THE EXPRESSION OF LTP
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DOI:
10.1016/0896-6273(95)90046-2
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发表时间:
1995-08-01
期刊:
影响因子:
16.2
通讯作者:
MALENKA, RC
MALENKA, RC
中科院分区:
医学1区
文献类型:
--
作者:
ISAAC, JTR;NICOLL, RA;MALENKA, RC

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最近的工作表明,在海马CA1区锥体细胞上表达NMDAR(NMDAR)的兴奋性突触可能不表达功能性AMPA受体(AMPAR),从而使这些突触在静息膜电位下保持沉默。根据这一假设,我们证明了当细胞保持在-60 mV时,可以刺激不产生可检测到的兴奋性突触后电流(EPSCs)的突触;然而,在正保持电位(+30到+60 mV)下,EPSCs可以被NMDAR拮抗剂D-APV完全阻断。当这些功能沉默的突触受到LTP诱导方案的影响时,由AMPAR介导的EPSCs出现并在实验期间保持不变。这种无声突触到功能性突触的转换被D-APV阻断。这些结果表明,LTP可能涉及AMPAR的修饰,在LTP之前,这些AMPAR要么不存在于突触后膜中,要么在电生理上是沉默的。这一机制可能解释了先前归因于突触前量子内容变化的几个实验结果。
Recent work has suggested that same proportion of excitatory synapses on hippocampal CA1 pyramidal cells that express NMDA receptors (NMDARs) may not express functional AMPA receptors (AMPARs), thus making these synapses silent at the resting membrane potential. In agreement with this hypothesis, we demonstrate here that it is possible to stimulate synapses that yield no detectable excitatory postsynaptic currents (EPSCs) when the cell is held at -60 mV; yet at positive holding potentials (+30 to +60 mV), EPSCs can be elicited that are completely blocked by the NMDAR antagonist, D-APV. When these functionally silent synapses are subjected to an LTP induction protocol, EPSCs mediated by AMPARs appear and remain for the duration of the experiment. This conversion of silent synapses to functional synapses is blocked by D-APV. These results suggest that LTP may involve modification of AMPARs that, prior to LTP, were either not present in the postsynaptic membrane or electrophysiologically silent. This mechanism may account for several experimental results previously attributed to presynaptic changes in quantal content.