Experience Dependent Plasticity in a fosGFP Mouse

描述(由申请人提供)： 识别构成感知、行为和学习的细胞和回路是当代神经科学的中心目标。虽然损伤分析、功能磁共振成像、2-脱氧葡萄糖研究和基因表达诱导等技术有助于确定负责特定功能的大脑区域，但这些方法在技术上是有限的。目前，还没有一种方法可以识别与活组织中特定功能相关的单个神经元。我们开发了一种转基因小鼠，其中绿色荧光蛋白(GFP)的表达受活性依赖基因c-fos启动子的调控。皮层和皮质下fosGFP的表达可以在神经元团的特异性激活后以区域受限的方式被诱导。这项建议旨在进一步确定fosGFP转基因小鼠的特征，并验证该工具作为一种对活体经验激活的神经元亚群进行解剖和电生理分析的方法。在经验依赖的可塑性过程中，单一晶须刺激诱导皮质晶须桶中c-fos和fosGFP的表达。为了更好地了解激活的神经元亚群中神经元基因的表达如何导致备用感觉输入的感受野扩大，将以fosGFP荧光神经元为靶点进行全细胞记录。FosGFP小鼠将被用来理解经验依赖性可塑性背后的解剖学和突触变化。这些小鼠能够在体内或体外表征由特定药物和行为操作激活的细胞和突触。这种方法将增强我们研究神经网络被经验和药物操纵激活和改变的方式的能力。

DESCRIPTION (provided by applicant): Identifying the cells and circuits that underlie perception, behavior, and learning is a central goal of contemporary neuroscience. Although techniques such as lesion analysis, fMRI, 2-deoxyglucose studies, and induction of gene expression have been helpful in determining the brain areas responsible for particular functions, these methods are technically limited. Currently there is no method that allows the identification of individual neurons that are associated with a particular function in living tissue. We have developed a strain of transgenic mice in which the expression of green fluorescent protein (GFP) is controlled by the promoter of the activity-dependent gene c-fos. Cortical and subcortical fosGFP expression could be induced in a regionally restricted fashion following specific activation of neuronal ensembles. This proposal seeks to further characterize the fosGFP transgenic mouse and validate this tool as a method for anatomical and electrophysiological analysis of neuronal subsets activated by in vivo experience. Single whisker stimulation induces c-fos and fosGFP expression in a cortical whisker barrel during experience-dependent plasticity. In order to better understand how neuronal gene expression in activated subsets of neurons leads to expansion of receptive fields for spared sensory inputs, fosGFP fluorescent neurons will be targeted for whole-cell recording. The fosGFP mice will be used to understand the anatomical and synaptic changes that underlie experience-dependent plasticity. These mice enable an in vivo or ex vivo characterization of the cells and synapses activated by particular pharmacological and behavioral manipulations. This method will enhance our ability to study the way neuronal networks are activated and changed by both experience and pharmacological manipulations.