Cellular Mechanisms of Intrinsic and Extrinsic Sensitization

内在和外在致敏的细胞机制

• 批准号: 0432683
• 负责人: Brian Burrell
• 金额: $ 12.06万
• 依托单位: University of South Dakota Main Campus
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0432683&HistoricalAwards=false
• 关键词: Cellular; Mechanisms; Intrinsic; Extrinsic; Sensitization

Burrell, Brian0213458Sensitization is a simple form of learning in which an animal's responses to environmental stimuli are enhanced. This form of behavioral plasticity is important because it contributes to processes of attention and arousal, as well as to more complex forms of learning such as classical (i.e. Pavlovian) conditioning. Typically, sensitization is induced by the delivery of a particularly strong or salient stimulus. This stimulus activates neurons that release modulatory neurotranmitters, which alter the neural circuit mediating the test behavior. Because the modulatory neurons are distinct from the neurons that mediate the test behavior, this process is referred to as extrinsic sensitization. However, there are many examples where sensitization is induced by a stimulus that is similar or identical to the stimulus that elicits the test behavior. In such situations, modulatory neurotransmitters are released by neurons within the circuit that mediates the test behavior. This is referred to as intrinsic or wind-up sensitization. Using the medicinal leech, the distinct physiological and cellular mechanisms of intrinsic and extrinsic sensitization will be examined. These experiments will combine electrophysiological recordings from single neurons with simultaneous monitoring of sensitization-induced changes in a defensive withdrawal reflex (shortening). Both forms of sensitization are observed in the leech shortening reflex and the leech nervous system is extremely well characterized, making it possible to record from single, identifiable neurons that are known to mediate this behavior.

敏化是一种简单的学习形式，动物对环境刺激的反应得到增强。这种形式的行为可塑性很重要，因为它有助于注意力和唤醒的过程，以及更复杂的学习形式，如经典（即巴甫洛夫）条件反射。通常，致敏是由一个特别强烈或显著的刺激引起的。这种刺激会激活神经元，释放调节性神经递质，从而改变调节测试行为的神经回路。因为调节神经元与调节测试行为的神经元不同，这个过程被称为外在敏化。然而，在许多例子中，敏化是由与引起测试行为的刺激相似或相同的刺激引起的。在这种情况下，调节神经递质被神经回路内的神经元释放，介导测试行为。这被称为内在敏化或发条敏化。利用药用水蛭，不同的生理和细胞机制的内在和外在的敏化将被检查。这些实验将结合单个神经元的电生理记录，同时监测致敏诱导的防御性退缩反射（缩短）的变化。在水蛭缩短反射中观察到两种形式的致敏，水蛭神经系统的特征非常明显，这使得从已知的介导这种行为的单个可识别的神经元中进行记录成为可能。