Systems-level electrophysiology for addiction and reward research

用于成瘾和奖励研究的系统级电生理学

• 批准号: 8672615
• 负责人: Sotiris Masmanidis
• 金额: $ 30.56万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8672615
• 关键词: Action Potentials; Acute; Address; Amygdaloid structure; Animals; Architecture; Area; Behavior; Behavioral; Behavioral Research; Blood - brain barrier anatomy; Brain; Brain Mapping; Brain region; Chemicals; Cognition; Coupled; Data; Development; Devices; Disease; Dopamine; Electrodes; Electronics; Electrophysiology (science); Functional Magnetic Resonance Imaging; Functional disorder; Gated Ion Channel; Genetic Techniques; Geometry; Goals; Hippocampus (Brain); Infusion procedures; Laboratories; Learning; Link; Location; Maps; Measurement; Measures; Mediating; Methodology; Methods; Midbrain structure; Molecular; Monitor; Mus; Nature; Neurons; Neurosciences; Optics; Output; Parkinson Disease; Pathway interactions; Pharmaceutical Preparations; Physiologic pulse; Play; Population; Prefrontal Cortex; Preparation; Protocols documentation; Reading; Recruitment Activity; Research; Resolution; Rewards; Role; Sampling; Scanning; Signal Transduction; Silicon; Site; Stimulus; Structure; System; Techniques; Technology; Testing; Time; Ventral Striatum; Ventral Tegmental Area; Width; Work; addiction; awake; base; behavior test; density; dopaminergic neuron; extracellular; implantable device; insight; instrument; instrumentation; interest; light gated; meetings; memory process; millisecond; miniaturize; minimally invasive; nanofabrication; nanoscale; neurophysiology; novel; optogenetics; pleasure; procedural memory; relating to nervous system; research study; response; reward circuitry; reward processing; scale up; tool; transmission process; two-dimensional

DESCRIPTION (provided by applicant): Addiction is closely linked with dysfunction of dopamine transmission in the brain circuitry of reward. Despite many decades of work, little is known about how systems-level phenomena in this pathway encode information, and how this information regulates behavior. The broad objective of this project is to introduce a new systems-level recording methodology to the arsenal of addiction and reward brain circuitry research. This study will demonstrate the feasibility of combining systems-level with molecular-level neuroscience, using implantable multi-electrodes to record extracellular single-unit activity and selective activation of neuronal subpopulations that mediate reward. Due to the highly interconnected and geometrically distributed nature of dopamine reward circuitry, it has been challenging to discern the network-wide dynamics of pathways recruited in reward-related behaviors such as addiction. To address this problem, the proposed recording instrument will deploy silicon shafts containing high-density electrodes at multiple locations in the brain. Other multi- electrode probe technologies lack the number of channels and geometry to record large numbers of neurons from deep and distributed areas required for this project. The devices proposed here will be built using nanofabrication methods to facilitate minimally invasive insertion of several multi-electrode-containing shafts throughout the mouse brain. Unlike traditional functional scanning techniques such as fMRI, the implantable devices will offer single-unit and sub-millisecond resolution. Functional control of activity in the pathway will be achieved by optogenetically activating dopaminergic neurons in the midbrain, mimicking the action of a rewarding stimulus. To test the ability to resolve systems-level activity of this dopaminergic neuron perturbation, we will implement two recording strategies. In the first approach, we will progressively scan a two-dimensional (2D) probe across an anatomical volume of interest, effectively constructing a high-resolution 3D map of action potential activity. In the second approach, we will simultaneously monitor the response of several brain areas associated with addiction, to capture the activity of up to 2,000 neurons in parallel in several distributed, but interconnected hubs in the mouse brain. In the long term the proposed devices and experimental protocols will provide a new window into the role of collective dynamic phenomena in the brain. Moreover, this technique will have broad impact on many aspects of neurophysiological and behavioral research, including reward-mediated learning and Parkinson's disease.

描述（由申请人提供）：成瘾与大脑奖赏回路中多巴胺传递功能障碍密切相关。 尽管经过几十年的研究，人们对这一通路中的系统水平现象如何编码信息以及这些信息如何调节行为知之甚少。 该项目的主要目标是将一种新的系统级记录方法引入成瘾和奖励脑回路研究的武器库。 这项研究将证明系统水平与分子水平神经科学相结合的可行性，使用植入式多电极记录细胞外单单位活动和介导奖励的神经元亚群的选择性激活。 由于多巴胺奖赏回路的高度互连和几何分布的性质，辨别在奖赏相关行为（如成瘾）中招募的通路的网络动态一直是一个挑战。 为了解决这个问题，拟议中的记录仪器将在大脑的多个位置部署含有高密度电极的硅轴。 其他 多电极探针技术缺乏通道的数量和几何形状来记录该项目所需的来自深部和分布式区域的大量神经元。 这里提出的设备将使用纳米纤维方法构建，以便于在整个小鼠大脑中微创插入几个含多电极的轴。 与传统的功能扫描技术（如fMRI）不同，植入式设备将提供单位和亚毫秒分辨率。 通过光遗传学激活中脑中的多巴胺能神经元，模拟奖励刺激的作用，将实现对通路中活性的功能控制。 为了测试分辨这种多巴胺能神经元扰动的系统水平活动的能力，我们将实施两种记录策略。 在第一种方法中，我们将逐步扫描二维（2D）探头在感兴趣的解剖体积，有效地构建动作电位活动的高分辨率3D地图。在第二种方法中，我们将同时监测与成瘾相关的几个大脑区域的反应，以捕获小鼠大脑中几个分布式但相互连接的枢纽中多达2,000个神经元的并行活动。 从长远来看，所提出的设备和实验方案将为研究大脑中集体动力现象的作用提供一个新的窗口。 此外，这项技术将对神经生理学和行为研究的许多方面产生广泛的影响，包括奖励介导的学习和帕金森病。