Role of intrabulbar CREB synthesis in olfactory learning

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，二尖瓣细胞的去抑制是嗅觉记忆形成的关键步骤，我们以前证明，在OB的GABA能机制参与控制的嗅觉学习在年轻的大鼠。在存在气味的情况下眼球内输注荷包牡丹碱后，动物表现出对中性气味的厌恶或参照。在出生后第12天，幼鼠表现出厌恶气味，它们沿着出生后第11天的足部电击。这些结果暗示OB作为嗅觉学习的关键站点。据报道，（cAMP反应结合蛋白）参与海马的可塑性，我们研究了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印迹分析显示磷酸化CREB（p CREB）在训练2小时后10分钟增加。3）CREB磷酸化相关酶的抑制剂阻止了嗅觉学习，Western blot检测pCREB表达无明显增加。

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.