Causally connecting neural activity to behavior with caged compounds

用笼状化合物将神经活动与行为因果联系起来

基本信息

批准号：
9116536
负责人：
SALEEM M NICOLA
金额：
$ 20.88万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9116536
关键词：
Address Adoption Agonist Animals Attention Behavior Behavior Disorders Behavioral Brain Brain Diseases Brain region Cannulas Cell Nucleus Chemicals Data Development Drug Addiction Drug abuse Effectiveness Electric Stimulation Electrodes Electrophysiology (science)Etiology Event Fiber Optics Functional disorder Glutamate Receptor Glutamates Goals Implant In Vitro Infusion procedures Injection of therapeutic agent Light Literature Mammals Measures Methods Motor Neurobiology Neurodegenerative Disorders Neurons Neurosciences Research Neurotransmitter Receptor Neurotransmitters Nucleus Accumbens Optics Performance Perfusion Pharmaceutical Preparations Pharmacological Treatment Problem Solving Rattus Receptor Activation Reporting Role Sensory Specificity Sucrose Synaptic Transmission Techniques Testing Tissues Training awake base behavioral pharmacology chromophore design drinking behavior drug reward in vivo interest irradiation neural circuit neurotransmitter agonist neurotransmitter antagonist novel optogenetics public health relevance relating to nervous system research study temporal measurement

项目摘要

DESCRIPTION (provided by applicant): Electrophysiological recording in awake animals allows neuroscientists to measure the neural circuit activity related to sensory or motor events. The information obtained from this approach is essential for analyzing how neural circuits produce behaviors related to drug addiction, including drug- and reward-seeking. However, with conventional electrophysiological methods, the data obtained in this way is purely correlative. In addition, merely recording neural activity is insufficient to determine how information encoded by neurons in one part of the circuit influences the representation of information by neurons in a "downstream" node - an important goal of neural circuit analysis. Here, we propose a method for manipulating neural transmission in a temporally and pharmacologically specific fashion, allowing the experimenter to establish both how upstream neurons contribute to recorded neural activity and how the activity causes a particular behavioral event. The proposed method will allow us to apply "caged" neurotransmitter agonists and antagonists to neurons whose activity we record in awake, behaving animals. Caged compounds are biologically active molecules that are rendered ineffective by a covalently attached chromophore. Application of light of the appropriate wavelength causes the bond to be broken, releasing the active compound. This method is widely used in electrophysiological studies in vitro, but no study to date has reported its application in vivo in awake behaving mammals. To apply this method in awake rats, we will take advantage of our expertise with application of drugs to neurons being recorded in awake animals. We will modify this approach by including light delivery into the brain via fiber optics, allowing us to uncage compounds introduced to the tissue via local perfusion. The proposed experiments will develop and test apparatus capable of such experiments, and demonstrate the effectiveness of the technique by determining how a glutamate receptor agonist influences behaviorally- relevant firing in the nucleus accumbens.

描述（由申请人提供）：清醒动物的电生理记录使神经科学家能够测量与感觉或运动事件相关的神经回路活动。从这种方法获得的信息对于分析神经回路如何产生与药物成瘾相关的行为至关重要。然而，使用传统的电生理学方法，以这种方式获得的数据是纯粹相关的。此外，仅仅记录神经活动不足以确定电路某一部分中的神经元编码的信息如何影响信息的表示。 “下游”节点中的神经元 - 神经回路分析的一个重要目标在这里，我们提出了一种以时间和药理学特定方式操纵神经传递的方法，使实验者能够确定上游神经元如何促进记录的神经活动。所提出的方法将允许我们将“笼中的”神经递质激动剂和拮抗剂应用于我们在清醒的行为动物中记录的神经元，笼中的化合物是具有生物活性的分子，而这些分子会因某种原因而变得无效。共价连接的发色团。应用适当波长的光导致键断裂，释放活性化合物。该方法广泛用于体外电生理学研究，但迄今为止没有研究报道其在清醒行为哺乳动物体内的应用。为了在清醒的大鼠中应用这种方法，我们将利用我们在清醒动物中记录的神经元上应用药物的专业知识，我们将通过光纤将光传输到大脑中来修改这种方法，从而使我们能够释放引入到大脑中的化合物。组织通过局部拟议的实验将开发和测试能够进行此类实验的设备，并通过确定谷氨酸受体激动剂如何影响伏隔核中行为相关的放电来证明该技术的有效性。