Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
PLoS One. 2012;7(8):e42143. doi: 10.1371/journal.pone.0042143. Epub 2012 Aug 10.
Glucocorticoid hormones, in interaction with noradrenaline, enable the consolidation of emotionally arousing and stressful experiences in rodents and humans. Such interaction is thought to occur at least partly in the basolateral nucleus of the amygdala (BLA) which is crucially involved in emotional memory formation. Extensive evidence points to long-term synaptic potentiation (LTP) as a mechanism contributing to memory formation. Here we determined in adolescent C57/Bl6 mice the effects of stress on LTP in the LA-BLA pathway and the specific roles of corticosteroid and β-adrenergic receptor activation in this process.
Exposure to 20 min of restraint stress (compared to control treatment) prior to slice preparation enhanced subsequent LTP induction in vitro, without affecting baseline fEPSP responses. The role of glucocorticoid receptors, mineralocorticoid receptors and β2-adrenoceptors in the effects of stress was studied by treating mice with the antagonists mifepristone, spironolactone or propranolol respectively (or the corresponding vehicles) prior to stress or control treatment. In undisturbed controls, mifepristone and propranolol administration in vivo did not influence LTP induced in vitro. By contrast, spironolactone caused a gradually attenuating form of LTP, both in unstressed and stressed mice. Mifepristone treatment prior to stress strongly reduced the ability to induce LTP in vitro. Propranolol normalized the stress-induced enhancement of LTP to control levels during the first 10 min after high frequency stimulation, after which synaptic responses further declined.
Acute stress changes BLA electrical properties such that subsequent LTP induction is facilitated. Both β-adrenergic and glucocorticoid receptors are involved in the development of these changes. Mineralocorticoid receptors are important for the maintenance of LTP in the BLA, irrespective of stress-induced changes in the circuit. The prolonged changes in BLA network function after stress may contribute to effective memory formation of emotional and stressful events.
糖皮质激素与去甲肾上腺素相互作用，使动物和人类能够巩固情绪激动和压力相关的经验。这种相互作用至少部分发生在杏仁核基底外侧核（BLA）中，该核在情绪记忆形成中起着至关重要的作用。大量证据表明，长时程突触增强（LTP）是促进记忆形成的机制之一。在这里，我们在青春期 C57/Bl6 小鼠中确定了应激对 LA-BLA 通路中 LTP 的影响，以及糖皮质激素和β-肾上腺素受体激活在该过程中的特定作用。
与对照处理相比，在切片制备前暴露于 20 分钟的束缚应激（与对照处理相比）增强了体外随后的 LTP 诱导，而不影响基线 fEPSP 反应。通过分别用米非司酮、螺内酯或普萘洛尔（或相应的载体）处理小鼠，然后进行应激或对照处理，研究了糖皮质激素受体、盐皮质激素受体和β2-肾上腺素受体在应激作用中的作用。在未受干扰的对照中，米非司酮和普萘洛尔的体内给药不会影响体外诱导的 LTP。相比之下，螺内酯在未受应激和应激的小鼠中均引起逐渐减弱的 LTP 形式。应激前用米非司酮处理强烈降低了体外诱导 LTP 的能力。普萘洛尔在高频刺激后 10 分钟内使应激诱导的 LTP 增强正常化至对照水平，之后突触反应进一步下降。
急性应激改变 BLA 的电生理特性，从而促进随后的 LTP 诱导。β-肾上腺素能和糖皮质激素受体都参与了这些变化的发展。盐皮质激素受体对于 BLA 中 LTP 的维持很重要，无论应激是否改变了回路。应激后 BLA 网络功能的长期变化可能有助于对情绪和压力相关事件的有效记忆形成。
