Department of Surgery, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Dr. Mail Code 7737, San Antonio, TX 78229-3900, USA.
Neurobiol Learn Mem. 2011 Sep;96(2):207-17. doi: 10.1016/j.nlm.2011.04.014. Epub 2011 May 6.
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.
内侧和外侧穿通路径向海马 CA3 区的投射显示出不同的长时程增强（LTP）诱导机制，分别依赖于 N-甲基-D-天冬氨酸（NMDA）和阿片受体。然而，内侧和外侧穿通路径向 CA3 区的投射具有共同激活的联想 LTP，这表明尽管它们在参与 LTP 诱导的受体上有所不同，但它们可能共享 LTP 诱导的共同下游机制。在这里，我们通过评估阿片受体在体内对内侧和外侧穿通路径向 CA3 区的联想 LTP 诱导的贡献来解决这种 LTP 诱导机制的相互作用。阿片受体拮抗剂纳洛酮或 Cys2-Tyr3-Orn5-Pen7-amide（CTOP）的局部应用通常会阻断外侧穿通路径-CA3 LTP 的诱导。然而，当通过强烈激活显示 NMDA 受体依赖性 LTP 的内侧穿通路径来诱导外侧穿通路径-CA3 突触的联想 LTP 时，这些阿片受体拮抗剂未能阻断其诱导。因此，非阿片能传入纤维的强烈激活可以替代外侧穿通路径 LTP 诱导所需的阿片受体激活。相反，当通过强烈激活阿片能外侧穿通路径来诱导内侧穿通路径-CA3 的联想 LTP 时，阿片受体拮抗剂会阻断其诱导。这些数据表明，当通过强烈激活阿片能传入系统来诱导时，内源性阿片肽有助于共同激活突触处的联想 LTP。这些数据进一步表明，联想 LTP 诱导受强烈刺激通路的受体机制调节。因此，尽管内侧和外侧穿通路径突触在 LTP 诱导机制上有所不同，但这些突触处的联想 LTP 具有共同的诱导下游机制。
