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给目标细胞。该提案旨在实时监测行为老鼠大脑中的特定神经递质多巴胺（DA）。该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最近取得进展之前，还无法实时查看所有神经递质。该提案中描述的实验的目标是通过直接观察执行颅内自我刺激（ICS）等行为任务的清醒大鼠大脑内不同子区域（特别是伏隔核（NA））的浓度波动来研究其在行为中的作用。在 ICS 过程中，动物按下杠杆以向选择的大脑通路提供电刺激，这种行为直接激活大脑奖励电路。与所有基于奖励的行为一样，这些事件发生在亚秒级的时间范围内，需要高速测量来进行观察。同时，我们将开发新的分析程序，以进一步获取在这些行为中获得的信息。这些实验将阐明多种基于奖励的行为（例如进食、性活动和药物滥用）背后的神经化学反应。该项目期间的具体目标是开发新技术（目标 1 和 4）并研究行为过程中的神经化学（目标 2 和 3）。它们是： 1. 采用多个电极同时探测行为过程中大脑的不同子区域，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直到最近才被认识到。瞬变是自发发生的，并且在响应预测奖励可用性的线索时尤其值得注意。 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. 开发和使用新的 NO 和 pH 传感器，用于行为动物。这两个目标在使用 DA 的大脑区域中都有动态浓度波动。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.