Dynamics of in vivo dopamine release

描述(申请人提供)：神经递质由神经元分泌，以亚秒的时间尺度将信息传递给目标细胞。这项建议旨在实时监测行为正常的大鼠大脑中一种特定的神经递质--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，因为在我们实验室最近的发展之前，无法实时查看所有神经递质。这项建议中描述的实验的目的是通过直接观察清醒大鼠在执行诸如颅内自我刺激(ICS)等行为任务的大鼠大脑中不同亚区，特别是伏隔核(NA)中的浓度波动，来研究其在行为中的作用。在ICS期间，动物按下一个杠杆来传递电刺激来选择大脑路径，这一行为直接激活了大脑奖励电路。与所有基于奖励的行为一样，这些事件发生在亚秒级时间尺度上，需要高速测量才能观察到它们。同时，我们将开发新的分析程序，以促进在这些行为中获得的信息。这些实验将阐明基于多重奖励的行为的神经化学反应，如进食、性行为和药物滥用。项目期间的具体目标是开发新技术(目标1和4)，并研究行为过程中的神经化学(目标2和3)。它们是：1.在行为过程中使用多个电极同时探测大脑不同的亚区，并开发减少背景电流影响的方法。2.探讨DA浓度瞬变的来源。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，尤其是在对预测奖励可获得性的暗示做出反应时。3.探讨DA在ICS中的具体作用。这一耐人寻味的行为缩短了正常行为，并允许直接调查与奖励有关的电路。4.开发和使用用于动物行为的NO和PH值的新传感器。这两个靶点在大脑中使用DA的区域都有动态的浓度波动。它们的检测将使人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.