Odor preference learning and memory modify GluA1phosphorylation and GluA1distribution in the neonate rat olfactory bulb: Testing the AMPA receptor hypothesis in an appetitive learning model
Odor preference learning and memory modify GluA1phosphorylation and GluA1distribution in the neonate rat olfactory bulb: Testing the AMPA receptor hypothesis in an appetitive learning model
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DOI：
10.1101/lm.1987711
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发表时间：
2011-05-01
影响因子：
2
通讯作者：
Harley, Carolyn W.
中科院分区：
文献类型：
--
作者：
Cui, Wen;Darby-King, Andrea;Harley, Carolyn W.
假设突触AMPA受体的增加介导学习和记忆。AMPA受体的增加在厌恶学习模型中有报道，尽管还不清楚它们是否与记忆维持有关。在这里，我们研究AMPA受体的变化在cAMP/PKA/CREB依赖的食欲学习模型：气味偏好学习的新生大鼠。大鼠幼鼠给予单一配对的薄荷和2毫克/公斤异丙肾上腺素，这产生了24小时，但不是48小时，薄荷偏好在7天大的大鼠幼鼠。GluA 1 PKA依赖性磷酸化在10分钟训练试验后10分钟达到峰值，并在90分钟内恢复到基线水平。在24小时，GluA 1亚基总体上没有变化，但在突触神经体中显着增加，与膜插入增加一致。免疫组化显示，在嗅球肾小球，嗅觉神经轴突的目标的GluA 1亚基显着增加。肾小球增加被认为是在3和24小时后，气味暴露在训练的小狗，但不是在控制小狗。GluA 1的增加没有看到早在10分钟后的训练，不再观察到48小时后，训练时气味偏好不再表示行为。因此，GluA 1膜表达增加的模式密切遵循记忆时间轴。此外，使用来自GluA 1亚基的羧基尾的干扰肽阻断GluA 1插入抑制了24 h气味偏好记忆，为我们的假设提供了因果支持。PKA介导的GluA 1磷酸化和随后的GluA 1插入可以共同提供增加的AMPA功能，以支持短期和长期的食欲记忆。
An increase in synaptic AMPA receptors is hypothesized to mediate learning and memory. AMPA receptor increases have been reported in aversive learning models, although it is not clear if they are seen with memory maintenance. Here we examine AMPA receptor changes in a cAMP/PKA/CREB-dependent appetitive learning model: odor preference learning in the neonate rat. Rat pups were given a single pairing of peppermint and 2 mg/kg isoproterenol, which produces a 24-h, but not a 48-h, peppermint preference in the 7-d-old rat pup. GluA1 PKA-dependent phosphorylation peaked 10 min after the 10-min training trial and returned to baseline within 90 min. At 24 h, GluA1 subunits did not change overall but were significantly increased in synaptoneurosomes, consistent with increased membrane insertion. Immunohistochemistry revealed a significant increase in GluA1 subunits in olfactory bulb glomeruli, the targets of olfactory nerve axons. Glomerular increases were seen at 3 and 24 h after odor exposure in trained pups, but not in control pups. GluA1 increases were not seen as early as 10 min after training and were no longer observed 48 h after training when odor preference is no longer expressed behaviorally. Thus, the pattern of increased GluA1 membrane expression closely follows the memory timeline. Further, blocking GluA1 insertion using an interference peptide derived from the carboxyl tail of the GluA1 subunit inhibited 24 h odor preference memory providing causative support for our hypothesis. PKA-mediated GluA1 phosphorylation and later GluA1 insertion could, conjointly, provide increased AMPA function to support both shortterm and long-term appetitive memory.