Alteration of neuronal firing properties after in vivo experience in a FosGFP transgenic mouse
Alteration of neuronal firing properties after in vivo experience in a FosGFP transgenic mouse
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DOI：
10.1523/jneurosci.4737-03.2004
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发表时间：
2004-07-21
影响因子：
5.3
通讯作者：
Dean, KL
中科院分区：
文献类型：
--
作者：
Barth, AL;Gerkin, RC;Dean, KL
识别感知、行为和学习的基础细胞和回路是当代神经科学的核心目标。虽然诸如病变分析、功能性磁共振成像、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，还没有允许识别和电生理表征与活组织中的特定功能相关的单个神经元的方法。我们开发了一种转基因小鼠品系，其中绿色荧光蛋白（GFP）的表达由活性依赖基因c-fos的启动子控制。这些小鼠能够体内或离体表征通过特定药理学和行为操作激活的细胞和突触。皮质和皮质下的fosGFP的表达可以诱导在特定的激活后的神经元系综的区域限制的方式。使用fosGFP小鼠来识别离散的皮层区域，我们发现感觉保留区域中的神经元快速调节动作电位阈值和尖峰频率以降低兴奋性。这种方法将提高我们的能力，研究神经元网络的激活和改变的经验和药理学操作。此外，由于激活的神经元可以在功能上进行表征，因此该工具可以开发出更好的药物，直接影响疾病状态中涉及的神经元。
Identifying the cells and circuits that underlie perception, behavior, and learning is a central goal of contemporary neuroscience. Although techniques such as lesion analysis, functional magnetic resonance imaging, 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 for the identification and electrophysiological characterization of individual neurons that are associated with a particular function in living tissue. We developed a strain of transgenic mice in which the expression of the green fluorescent protein (GFP) is controlled by the promoter of the activity-dependent gene c-fos. These mice enable an in vivo or ex vivo characterization of the cells and synapses that are activated by particular pharmacological and behavioral manipulations. Cortical and subcortical fosGFP expression could be induced in a regionally restricted manner after specific activation of neuronal ensembles. Using the fosGFP mice to identify discrete cortical areas, we found that neurons in sensory-spared areas rapidly regulate action potential threshold and spike frequency to decrease excitability. This method will enhance our ability to study the way neuronal networks are activated and changed by both experience and pharmacological manipulations. In addition, because activated neurons can be functionally characterized, this tool may enable the development of better pharmaceuticals that directly affect the neurons involved in disease states.