Compartmentalized Ca2+ channel regulation at divergent mossy-fiber release sites underlies target cell-dependent plasticity

Compartmentalized Ca2+ channel regulation at divergent mossy-fiber release sites underlies target cell-dependent plasticity
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DOI:
10.1016/j.neuron.2006.08.032
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发表时间:
2006-11-09
期刊:
影响因子:
16.2
通讯作者:
McBain, Chris J.
McBain, Chris J.
中科院分区:
医学1区
文献类型:
--
作者:
Pelkey, Kenneth A.;Topolnik, Lisa;McBain, Chris J.

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海马苔藓纤维(MF)通过解剖学上不同的突触前元件支配CA 3靶:MF终扣(MFB)支配锥体细胞(PYR),而MFB的丝状伪足延伸(Fils)支配灵芝中间神经元(SLIN)。令人惊讶的是,相同的高频刺激(HFS)协议诱导突触前表达的LTP和LTD在PYR和SLIN输入,分别。这种可塑性的差异分布表明,相邻的,功能上不同的突触前元件沿着相同的轴突作为自主的计算元件能够独立地修改释放。事实上,我们报告说,HFS持续抑制电压门控钙通道(VGCC)的功能在FII终端,留下MFB VGCC不变,尽管类似的贡献N-和P/Q-型VGCC传输在每个终端。选择性Fil VGCC抑制是由HFS诱导的mGluR 7活化导致持续的P/Q型VGCC抑制引起的。因此,mGluR 7定位于MF-SLIN末端而不是MFB允许MF-SLIN LTD通过抑制突触前VGCC功能表达,而MF-PYR可塑性独立于VGCC改变进行。
Hippocampal mossy fibers (MFs) innervate CA3 targets via anatomically distinct presynaptic elements: MF boutons (MFBs) innervate pyramidal cells (PYRs), whereas filopodial extensions (Fils) of MFBs innervate st. lucidum interneurons (SLINs). Surprisingly, the same high-frequency stimulation (HFS) protocol induces presynaptically expressed LTP and LTD at PYR and SLIN inputs, respectively. This differential distribution of plasticity indicates that neighboring, functionally divergent presynaptic elements along the same axon serve as autonomous computational elements capable of modifying release independently. Indeed we report that HFS persistently depresses voltage-gated calcium channel (VGCC) function in Fil terminals, leaving MFB VGCCs unchanged despite similar contributions of N- and P/Q-type VGCCs to transmission at each terminal. Selective Fil VGCC depression results from HFS-induced mGluR7 activation leading to persistent P/Q-type VGCC inhibition. Thus, mGluR7 localization to MF-SLIN terminals and not MFBs allows for MF-SLIN LTD expression via depressed presynaptic VGCC function, whereas MF-PYR plasticity proceeds independently of VGCC alterations.