β-Adrenergic receptor activation during distinct patterns of stimulation critically modulates the PKA-dependence of LTP in the mouse hippocampus
β-Adrenergic receptor activation during distinct patterns of stimulation critically modulates the PKA-dependence of LTP in the mouse hippocampus
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DOI：
10.1101/lm.829208
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发表时间：
2008-05-01
影响因子：
2
通讯作者：
Nguyen, Peter V.
中科院分区：
文献类型：
--
作者：
Gelinas, Jennifer N.;Tenorio, Gustavo;Nguyen, Peter V.
β-肾上腺素能受体（β-AR）的激活可增强海马记忆巩固和长时程增强（LTP），这是记忆存储的一种可能机制。与 β-AR 激活相关的一种信号传导途径是 cAMP-PKA 途径。 PKA 对于海马长期记忆的巩固和某些形式的持久海马 LTP 的表达至关重要。 β-AR 激活如何影响不同刺激频率引起的 LTP 的 PKA 依赖性和持久性？在这里，我们使用体外电生理学来证明刺激模式决定受 beta-AR 激活影响的 LTP 的时间阶段。此外，只有特定的刺激模式才能在 beta-AR 激活后招募 PKA 依赖性 LTP。由于 PKA 活性的药理学或遗传缺陷而产生的 PKA 依赖性 LTP 维持的损害也可以通过同时激活 β-AR 来消除。总而言之，我们的数据表明，根据突触刺激的模式，β-AR 的激活可以控制 PKA 依赖性和突触可塑性的持久性。我们认为这可能允许神经调节受体微调神经信息处理，以满足众多突触活动概况所施加的要求。这是一种“化塑性”，可以控制海马长期记忆巩固的功效。
Activation of beta-adrenergic receptors (beta-ARs) enhances hippocampal memory consolidation and long-term potentiation (LTP), a likely mechanism for memory storage. One signaling pathway linked to beta-AR activation is the cAMP-PKA pathway. PKA is critical for the consolidation of hippocampal long-term memory and for the expression of some forms of long-lasting hippocampal LTP. How does beta-AR activation affect the PKA-dependence, and persistence, of LTP elicited by distinct stimulation frequencies? Here, we use in vitro electrophysiology to show that patterns of stimulation determine the temporal phase of LTP affected by beta-AR activation. In addition, only specific patterns of stimulation recruit PKA-dependent LTP following beta-AR activation. Impairments of PKA-dependent LTP maintenance generated by pharmacologic or genetic deficiency of PKA activity are also abolished by concurrent activation of beta-ARs. Taken together, our data show that, depending on patterns of synaptic stimulation, activation of beta-ARs can gate the PKA-dependence and persistence of synaptic plasticity. We suggest that this may allow neuromodulatory receptors to fine-tune neural information processing to meet the demands imposed by numerous synaptic activity profiles. This is a form of "metaplasticity" that could control the efficacy of consolidation of hippocampal long-term memories.