THE NEUROBIOLOGY OF EARLY LEARNING

我们建议继续我们的神经生物学的综合研究 早期的嗅觉学习。我们的重点将放在神经递质和 神经营养机制参与脑内神经行为改变 早期嗅觉学习诱导大鼠嗅球形成。 利昂博士将阐述去甲肾上腺素在形成和发展中的作用 判断早期嗅觉学习的表现：反应 嗅球神经元对去甲肾上腺素能的刺激； β-去甲肾上腺素能受体在发育过程中的瞬时表达 去甲肾上腺素能受体在血管紧张素转换酶基因表达中的作用 神经行为反应；球的条件性增加的功能 去甲肾上腺素；终止敏感的 去甲肾上腺素是否为不同疾病的共同危险因素 强化刺激；“过度刺激”是否阻断早期 嗅觉学习是由于去甲肾上腺素能反应的变化。 Gall博士将使用原位杂交技术来确定： 嗅球内即刻和早期的空间定位 对不同刺激条件下出现的气味作出反应的基因； 对嗅觉偏好训练的反应；对小说的双重反应 以及学习到的嗅觉提示；球状反应可能的锐化 在发育过程中；早期嗅觉剥夺对 随后的嗅球反应；是否在即刻早期改变 基因可以与细胞表达的变化联系在一起 前脑啡肽原和酪氨酸羟基酶。 内夫博士将研究GAP-43在早期多巴胺反应中的作用。 鳞茎：分析发育中的鳞茎对GAP-43的表达 和蛋白激酶C，一个潜在的GAP-43稳定因素 确定GAP-43和蛋白激酶C是否发生变化 早期嗅觉学习后，改变GAP-43在大鼠模型中的表达 用重组病毒球茎，然后测定多巴胺的变化 对早期嗅觉偏好训练的反应；构建 携带突变型GAP-43抑制多巴胺的转基因小鼠 然后确定它们对嗅觉偏好的反应 训练。

We propose to continue our integrated investigation of the neurobiology of early olfactory learning. Our focus will be on the neurotransmitter and neurotrophic mechanisms involved in the neurobehavioral changes within the rat olfactory bulb induced by early olfactory learning. Dr. Leon will address the role of noradrenaline in the formation and expression of early olfactory learning by determining: the response of olfactory bulb neurons to noradrenergic stimulation; the possibility of a transient expression of beta noradrenergic receptors in the developing bulb; the role of alpha noradrenergic receptors in the expression of the neurobehavioral response; the function of the conditioned increase in bulb noradrenaline; the mechanism underlying the termination of the sensitive period; whether noradrenaline is a common critical factor for different reinforcing stimulation; whether "overstimulation" blocking of early olfactory learning is due to changes in noradrenergic responses. Dr. Gall will use the in situ hybridization technique to determine: the spatial localization within the olfactory bulb for both immediate early genes in response to odors presented under different stimulus conditions; the response to olfactory preference training; the dual response to novel and learned olfactory cues; the possible sharpening of the bulb response during development; the effects of early olfactory deprivation on subsequent olfactory bulb responses; whether changes in the immediate early genes can be linked to cellular changes in the expression of preproenkephalin and tyrosine hydroxylase. Dr. Neve will examine the role of GAP-43 in the early dopamine response of the bulb by: analyzing developing bulb for the expression of both GAP-43 and protein kinase C, a potential factor in the stabilization of GAP-43 mRNA; determining whether there is a change in GAP-43 and protein kinase C after early olfactory learning; changing the expression of GAP-43 in the bulb with a recombinant virus, then determining the change in dopamine release in response to early olfactory preference training; constructing transgenic mice that have a mutant form of GAP-43 to suppress dopamine release and then determining their response to olfactory preference training.