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Role of intrabulbar CREB synthesis in olfactory learning

球内 CREB 合成在嗅觉学习中的作用

基本信息

批准号：
12680777
负责人：
OKUTANI Fumino
金额：
$ 2.3万
依托单位：
Kochi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680777/
关键词：
Behavioral pharmacology CREB (cyclic AMP response binding protein)Learning Olfaction Synaptic plasticity Western blotting Young rats

项目摘要

Preweanling young rats prior to eye opening are dependent on somatosensory and olfactory function for survival, as they can learn their dam's odor and approach her without visual information. In order to establish olfactory learning, the pairing of odor and somatosensory stimulation is crucial. Centrifugal noradrenergic activation through the locus coeruleus by a somatosensory stimulus is implicated in olfactory learning. Within the olfactory bulb (OB), the noradrenergic innervation modulates the efficacy of dendrodendritic synapses between the mitral and granule cells. At the dendrodendritic reciprocal synapses, mitral cell activity is inhibited by GABA released from the granule cells. LC activation is thought to modulate GABAergic inhibition of the mitral cells by the granule cells. It is noteworthy that disinhibition of the mitral cells is a crucial step in the formation of an olfactory memory.We previously demonstrated that GABAergic mechanisms in the OB are involved in the control of olfactory learning in young rats. After intrabulbar infusion of bicuculline in the presence of an odor, animals show an aversion to or reference for the neutral odor. On post-natal day 12, young rats show an aversion to an odor to which they had been exposed along with presentations of foot shock on post-natal day 11. These results implicate the OB as a critical site for olfactory learning. Since it has been reported CREB(cyclic AMP response binding protein) involves plasticity in the hippocampus, we examined whether CREB is involved in olfactory learning in young rats.1) CREB antisense infusion blocks olfactory learning.2) Western blot analysis shows that phosphorylated CREB (p CREB) increases 10 minutes after the training for 2 hours.3) Inhibitors of enzymes involved in CREB phosphrylation prevent olfactory learning, and concomitantly result in no increase of pCREB in Western blot.

在睁开眼睛之前断奶的幼鼠依赖体感和嗅觉功能生存，因为它们可以在没有视觉信息的情况下学习它们的气味并接近它们。为了建立嗅觉学习，气味和体感刺激的搭配是至关重要的。躯体感觉刺激通过蓝斑的去甲肾上腺素能离心性激活与嗅觉学习有关。在嗅球(OB)内，去甲肾上腺素能神经支配调节二尖瓣和颗粒细胞之间树-树突触的效能。在树-树相互突触，二尖瓣细胞的活动受到颗粒细胞释放的GABA的抑制。LC的激活被认为调节颗粒细胞对二尖瓣细胞的GABA能抑制作用。值得注意的是，二尖瓣细胞的解除抑制是形成嗅觉记忆的关键步骤。我们以前证明了OB区的GABA能机制参与了幼鼠嗅觉学习的控制。在有气味的情况下球内注射荷包牡丹碱后，动物表现出对中性气味的厌恶或参照。在出生后第12天，幼鼠表现出对它们所接触到的气味的厌恶，并在出生后第11天出现脚部电击。这些结果表明OB是嗅觉学习的关键场所。由于已有报道CREB(环磷酸腺苷反应结合蛋白)参与了年轻大鼠的嗅觉学习，我们探讨了CREB是否参与了年轻大鼠的嗅觉学习。1)CREB反义输注阻断了嗅觉学习。2)Western印迹分析显示，训练2小时后10分钟，磷酸化的CREB(P CREB)增加。3)CREB磷酸化参与的酶的抑制剂阻止了嗅觉学习，同时导致Western印迹中的pCREB没有增加。