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Molecular mechanism of intrabulbar plasticity (BDNF-CREB cascade)

球内可塑性的分子机制（BDNF-CREB级联）

基本信息

批准号：
15500216
负责人：
OKUTANI Fumino
金额：
$ 2.37万
依托单位：
Kochi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

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 showed the results that intrabulbar infusion of the GABA receptor antagonist, … More bicuculline facilitates olfactory learning. 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. And we tried to clarify synaptic plasticity in the OB using electrophysiology.1)Only long-term olfactory memory was prevented by CREB antisense infusion, but short-term memory was intact.2)Western blot analysis shows that phosphorylated CREB(pCREB) increases 10 minutes after the training for 2 hours.3)MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase) phosphorylates CREB.4)Long-term potentiation(LTP) was induced in field EPSPs recorded in the granule cell layer in the OB by tetanic stimulation of the lateral olfactory tract.5)In the presence of noradrenaline subthreshold stimulation was capable of inducing LTP.6)Common properties between electrophysiology and behavior pharmacology indicate that synaptic plasticity at the dendrodendritic synapses is a major candidate for neural mechanisms underlying aversive olfactory learning in young rats. Less

在睁眼之前，断奶前的幼鼠依赖于躯体感觉和嗅觉功能生存，因为它们可以学习母鼠的气味，并在没有视觉信息的情况下接近母鼠。为了建立嗅觉学习，气味和体感刺激的配对是至关重要的。体感刺激通过蓝斑的离心去甲肾上腺素能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的树突突触的功效。在树-树相互突触中，颗粒细胞释放的GABA抑制了二尖瓣细胞的活动。LC激活被认为调节颗粒细胞对二尖瓣细胞的GABA能抑制。值得注意的是，僧帽细胞的去抑制是嗅觉记忆形成的关键步骤。我们以前的结果表明，球内注入GABA受体拮抗剂， ...更多信息荷包牡丹碱促进嗅觉学习。这些结果暗示OB作为嗅觉学习的关键站点。由于CREB（环磷酸腺苷反应结合蛋白）已被报道涉及海马的可塑性，我们研究CREB是否参与幼鼠的嗅觉学习。我们试图利用电生理学来阐明OB中的突触可塑性。1）CREB反义输注仅阻止了长时程嗅觉记忆，2）Western blot分析显示，在训练2小时后10分钟，磷酸化CREB（pCREB）表达增加（丝裂原活化蛋白激酶/细胞外信号调节激酶）磷酸化CREB。4）长时程增强（LTP）强直刺激外侧嗅束，在嗅球颗粒细胞层记录到的EPSP中诱发LTP。5）在去甲肾上腺素存在下，阈下刺激能够诱发LTP。6）电生理学和行为药理学之间的共同特性表明，在树-树突触的突触可塑性是一个主要的候选人，在年轻大鼠的厌恶嗅觉学习的神经机制。少