Synergistic activation of dopamine D1 and TrkB receptors mediate gain control of synaptic plasticity in the basolateral amygdala.
Synergistic activation of dopamine D1 and TrkB receptors mediate gain control of synaptic plasticity in the basolateral amygdala.
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DOI：
10.1371/journal.pone.0026065
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Rainnie DG
中科院分区：
文献类型：
--
作者：
Li C;Dabrowska J;Hazra R;Rainnie DG
恐惧记忆的形成被认为需要多巴胺、脑源性神经营养因子（BDNF）和锌在基底外侧杏仁核（BLA）的释放，以及BLA主神经元的长期增强（LTP）的诱导。然而，迄今为止没有研究表明BLA中这些过程之间存在任何关系。在这里，我们使用体外全细胞膜片钳记录BLA主要神经元，研究多巴胺、BDNF和锌释放如何相互作用以调节BLA的LTP诱导。LTP是由θ脉冲刺激（TBS）方案或间隔5倍高频刺激（5xHFS）诱导的。值得注意的是，TBS和5xHFS诱导的LTP均被多巴胺D1受体拮抗剂SCH23390完全阻断。LTP的诱导也被BDNF清除剂TrkB-FC、锌螯合剂DETC以及基质金属蛋白酶（MMPs）抑制剂gallardin阻断。相反，先前应用多巴胺再摄取抑制剂GBR12783或D1受体激动剂SKF39393，在亚阈值HFS方案（2xHFS）下诱导稳健和稳定的LTP，而亚阈值HFS通常不会诱导LTP。同样，用TrkB受体激动剂或BDNF事先激活TrkB受体，也会降低ltp诱导的阈值，这一效应被MEK抑制剂阻断，但不被锌螯合阻断。有趣的是，TrkB受体激动剂诱导的LTP阈值降低被预先应用SCH23390完全阻断，而GBR12783诱导的LTP阈值降低被预先应用TrkB- fc阻断。总之，我们的研究结果提示了一种细胞机制，即在BLA主神经元中LTP诱导的阈值严重依赖于细胞外环境中的多巴胺水平以及突触后D1和TrkB受体的协同激活。此外，TrkB受体的激活似乎依赖于锌的同时释放和MMPs的激活。
Fear memory formation is thought to require dopamine, brain-derived neurotrophic factor (BDNF) and zinc release in the basolateral amygdala (BLA), as well as the induction of long term potentiation (LTP) in BLA principal neurons. However, no study to date has shown any relationship between these processes in the BLA. Here, we have used in vitro whole-cell patch clamp recording from BLA principal neurons to investigate how dopamine, BDNF, and zinc release may interact to modulate the LTP induction in the BLA. LTP was induced by either theta burst stimulation (TBS) protocol or spaced 5 times high frequency stimulation (5xHFS). Significantly, both TBS and 5xHFS induced LTP was fully blocked by the dopamine D1 receptor antagonist, SCH23390. LTP induction was also blocked by the BDNF scavenger, TrkB-FC, the zinc chelator, DETC, as well as by an inhibitor of matrix metalloproteinases (MMPs), gallardin. Conversely, prior application of the dopamine reuptake inhibitor, GBR12783, or the D1 receptor agonist, SKF39393, induced robust and stable LTP in response to a sub-threshold HFS protocol (2xHFS), which does not normally induce LTP. Similarly, prior activation of TrkB receptors with either a TrkB receptor agonist, or BDNF, also reduced the threshold for LTP-induction, an effect that was blocked by the MEK inhibitor, but not by zinc chelation. Intriguingly, the TrkB receptor agonist-induced reduction of LTP threshold was fully blocked by prior application of SCH23390, and the reduction of LTP threshold induced by GBR12783 was blocked by prior application of TrkB-FC. Together, our results suggest a cellular mechanism whereby the threshold for LTP induction in BLA principal neurons is critically dependent on the level of dopamine in the extracellular milieu and the synergistic activation of postsynaptic D1 and TrkB receptors. Moreover, activation of TrkB receptors appears to be dependent on concurrent release of zinc and activation of MMPs.
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影响因子：
4.7
作者：
Huber, KM;Sawtell, NB;Bear, MF
通讯作者：
Bear, MF
DOI：
10.1073/pnas.0912973107
发表时间：
2010-04-13
影响因子：
11.1
作者：
Chen, Lulu Y.;Rex, Christopher S.;Gall, Christine M.
通讯作者：
Gall, Christine M.
影响因子：
1.9
作者：
Greba, Q;Kokkinidis, L
通讯作者：
Kokkinidis, L
影响因子：
11.4
作者：
Hartmann, M;Heumann, R;Lessmann, V
通讯作者：
Lessmann, V
影响因子：
4.7
作者：
Gao, Can;Sun, Xiu;Wolf, Marina E.
通讯作者：
Wolf, Marina E.