Dynamics of in vivo dopamine release

描述（由申请人提供）：神经递质由神经元分泌，并以亚秒级的时间尺度将信息传递到靶细胞。这项提议是针对实时监测一种特定的神经递质，多巴胺（DA），在大脑中的行为大鼠。传感技术在碳纤维电极上采用快速扫描循环伏安法。DA是我们的目标，因为它是大脑“奖励”系统的核心角色。它的确切作用尚不清楚，因为直到我们实验室的最新进展，所有神经递质的实时视图都不可用。在这个建议中描述的实验的目标是调查其在行为中的作用，通过直接观察其浓度波动在不同的亚区域内的大脑，特别是在清醒的大鼠执行行为任务，如颅内自我刺激（ICS）的丘脑核（NA）。在ICS期间，动物按下杠杆以提供电刺激来选择大脑通路，这是一种直接激活大脑奖励回路的行为。与所有基于奖励的行为一样，事件发生在亚秒级的时间尺度上，需要高速测量来观察它们。同时，我们将开发新的分析程序，以进一步分析在这些行为中获得的信息。这些实验将阐明神经化学反应，这些反应是基于多种奖励的行为，如喂食，性活动和药物滥用。项目期间的具体目标是开发新技术（目标1和4）和研究行为过程中的神经化学（目标2和3）。分别是：1.使用多个电极在行为期间同时探测大脑的不同子区域，并开发减少背景电流影响的方法。2.研究DA浓度瞬变的起源。DA神经传递的这些动态特征最近才被认识到。瞬变是自发发生的，在对预测奖励可用性的线索做出反应时尤其明显。3.探讨DA在ICS中的具体作用。这种有趣的行为使正常行为短路，并允许直接研究涉及奖励的电路。4.开发和使用用于行为动物的新型NO和pH传感器。这两个目标在大脑中使用DA的区域都有动态的浓度波动，它们的检测将使我们能够更全面地了解与奖励相关的化学变化。

DESCRIPTION (provided by applicant): Neurotransmitters are secreted by neurons and relay messages to target cells on a subsecond time scale. This proposal is directed at real-time monitoring of a specific neurotransmitter, dopamine (DA), in the brain of behaving rats. The sensing technology employs fast-scan cyclic voltammetry at carbon-fiber electrodes. DA is our target because it is a central player in the brain 'reward' system. It precise role is unclear because, until recent developments in our laboratory, a real-time view of all neurotransmitters was unavailable. The goal of the experiments described in this proposal is to investigate its role in behavior by directly observing its concentration fluctuations in distinct subregions within the brain, particularly the nucleus accumbens (NA), in awake rats executing behavioral tasks such as intracranial self-stimulation (ICS). During ICS, animals depress a lever to deliver an electrical stimulation to select brain pathways, a behavior that directly activates the brain reward circuitry. As with all reward-based behaviors, the events occur on a subsecond time scale, requiring high speed measurements for their observation. Simultaneously, we will be developing new analytical procedures that will further the information obtained during these behaviors. These experiments will clarify the neurochemical responses that underlie multiple reward based behaviors such as feeding, sexual activities, and drug abuse. The specific aims for the project period are to develop new technology (Aims 1 and 4) and investigate the neurochemistry during behavior (Aims 2 and 3). They are: 1. To employ multiple electrodes to simultaneously probe different subregions of the brain during behavior and to develop methods to reduce the impact of the background current. 2. To investigate the origin of DA concentration transients. These dynamic features of DA neurotransmission have only been recognized recently. Transients occur spontaneously and are particularly notable in response to cues that predict reward availability. 3. To investigate the specific role of DA during ICS. This intriguing behavior short circuits normal behaviors and allows the the circuitry involved in reward to be directly investigated. 4. To develop and use new sensors for NO and pH for use in behaving animals. Both targets have dynamic concentration fluctuations in regions of the brain that use DA. Their detection will enable a more complete view of the chemical changes associated with reward.