Homer 1a gates the induction mechanism for endocannabinoid-mediated synaptic plasticity.
Homer 1a gates the induction mechanism for endocannabinoid-mediated synaptic plasticity.
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Homer 1a 控制内源性大麻素介导的突触可塑性的诱导机制。
DOI：
10.1523/jneurosci.4603-09.2010
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发表时间：
2010-02-24
期刊：
影响因子：
--
通讯作者：
Thayer SA
中科院分区：
文献类型：
--
作者：
Roloff AM;Anderson GR;Martemyanov KA;Thayer SA
在海马兴奋性突触，内源性大麻素（eCBs）介导两种形式的逆行突触抑制，这种抑制是由突触后去极化或代谢性谷氨酸受体（mGluRs）的激活引起的。分子支架家族提供空间组织来调节突触后信号级联，包括那些由mGluRs激活的信号级联。荷马1a （H1a）即时早期基因的表达产生一个短荷马蛋白，缺乏荷马寡聚化所需的结构域，使其能够解耦荷马组装。在这里，我们报道了H1a差异调节两种形式的ecb介导的突触可塑性，去极化诱导的兴奋抑制（DSE）和代谢抑制兴奋（MSE）。记录培养海马神经元的兴奋性突触后电流，15 s去极化至0 mV诱发的DSE和I型mGluR激动剂诱发的MSE。在同一突触，H1a的表达增强了DSE，抑制了MSE。许多生理上重要的刺激启动H1a表达，包括脑源性神经营养因子（BDNF）。用BDNF处理海马培养物可增加H1a和解偶联homer1c-GFP簇的转录。BDNF抑制MSE，增强DSE。因此，H1a表达的生理变化通过将mGluR与eCB的产生解偶联而开启了eCB介导的突触可塑性的诱导途径。
At hippocampal excitatory synapses, endocannabinoids (eCBs) mediate two forms of retrograde synaptic inhibition that are induced by postsynaptic depolarization or activation of metabotropic glutamate receptors (mGluRs). The homer family of molecular scaffolds provides spatial organization to regulate postsynaptic signaling cascades, including those activated by mGluRs. Expression of the homer 1a (H1a) immediate early gene produces a short homer protein that lacks the domain required for homer oligomerization, enabling it to uncouple homer assemblies. Here, we report that H1a differentially modulates two forms of eCB-mediated synaptic plasticity, depolarization-induced suppression of excitation (DSE) and metabotropic suppression of excitation (MSE). Excitatory postsynaptic currents were recorded from cultured hippocampal neurons and DSE evoked by a 15 s depolarization to 0 mV and MSE evoked by a type I mGluR agonist. Expression of H1a enhanced DSE and inhibited MSE at the same synapse. Many physiologically important stimuli initiate H1a expression including brain derived neurotrophic factor (BDNF). Treating hippocampal cultures with BDNF increased transcription of H1a and uncoupled homer1c-GFP clusters. BDNF treatment blocked MSE and enhanced DSE. Thus, physiological changes in H1a expression gate the induction pathway for eCB-mediated synaptic plasticity by uncoupling mGluR from eCB production.