Endogenous opioid peptides contribute to associative LTP in the hippocampal CA3 region.
Endogenous opioid peptides contribute to associative LTP in the hippocampal CA3 region.
复制标题
内源性阿片肽有助于海马 CA3 区的联合 LTP。
DOI：
10.1016/j.nlm.2011.04.014
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发表时间：
2011
影响因子：
2.7
通讯作者：
Derrick,BrianE
中科院分区：
文献类型：
--
作者：
Martinez,CarloO;Do,VietH;Derrick,BrianE
向海马CA3区的内侧和外侧穿支路投射分别表现出不同的长时程增强(LTP)诱导、N-甲基-d-天冬氨酸(NMDA)和阿片受体依赖机制。然而，向CA3区的内侧和外侧穿支路径投射显示LTP与共激活有关，这表明尽管它们参与LTP诱导的受体不同，但它们可能具有共同的LTP诱导下游机制。在这里，我们通过评估阿片受体对体内CA3区内侧和外侧穿支路径投射之间联合LTP诱导的贡献来讨论LTP诱导机制的这种相互作用。局部应用阿片受体拮抗剂纳洛酮或Cys2-Tyr3-Orn5-Pen7-酰胺(CTOP)通常可阻断侧支通路-CA3LTP的诱导。然而，这些阿片受体拮抗剂不能阻断外侧穿支通路-CA3突触的关联性LTP，因为它是由表现NMDAR依赖的LTP的内侧穿支通路的强烈共激活诱导的。因此，非阿片能传入的强烈激活可以替代外侧穿支路LTP诱导所需的阿片受体激活。相反，当阿片受体拮抗剂强烈共激活阿片能外侧穿支通路时，内侧穿支通路-CA3相关的LTP被阿片受体拮抗剂阻断。这些数据表明，当阿片能传入系统强烈共激活时，内源性阿片肽参与了共激活突触的关联性LTP。这些数据进一步表明，联合LTP的诱导受到强刺激途径的受体机制的调节。因此，尽管内侧和外侧穿支路突触的LTP诱导机制不同，但这些突触的联合LTP具有共同的下游诱导机制。
The medial and lateral perforant path projections to the hippocampal CA3 region display distinct mechanisms of long-term potentiation (LTP) induction, N-methyl-d-aspartate (NMDA) and opioid receptor dependent, respectively. However, medial and lateral perforant path projections to the CA3 region display associative LTP with coactivation, suggesting that while they differ in receptors involved in LTP induction they may share common downstream mechanisms of LTP induction. Here we address this interaction of LTP induction mechanisms by evaluating the contribution of opioid receptors to the induction of associative LTP among the medial and lateral perforant path projections to the CA3 region in vivo. Local application of the opioid receptor antagonists naloxone or Cys2-Tyr3-Orn5-Pen7-amide (CTOP) normally block induction of lateral perforant path-CA3 LTP. However, these opioid receptor antagonists failed to block associative LTP in lateral perforant path-CA3 synapses when it was induced by strong coactivation of the medial perforant pathway which displays NMDAR-dependent LTP. Thus strong activation of non-opioidergic afferents can substitute for the opioid receptor activation required for lateral perforant path LTP induction. Conversely, medial perforant path-CA3 associative LTP was blocked by opioid receptor antagonists when induced by strong coactivation of the opioidergic lateral perforant path. These data indicate endogenous opioid peptides contribute to associative LTP at coactive synapses when induced by strong coactivation of an opioidergic afferent system. These data further suggest that associative LTP induction is regulated by the receptor mechanisms of the strongly stimulated pathway. Thus, while medial and lateral perforant path synapses differ in their mechanisms of LTP induction, associative LTP at these synapses share common downstream mechanisms of induction.