Appetitive/aversive encoding in the nucleus accumbens

伏隔核中的食欲/厌恶编码

• 批准号: 7532171
• 负责人: Sharif A. Taha
• 金额: $ 15.05万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-25 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7532171
• 关键词: Addictive Behavior; Animals; Appetitive Behavior; Aversive Stimulus; Behavior; Behavior Control; Behavioral; Behavioral Paradigm; Brain; Brain region; Class; Condition; Consummatory Behavior; Consumption; Costs and Benefits; Cues; Data; Decision Making; Disease; Disinhibition; Drug usage; Eating; Electrodes; Electrophysiology (science); Feeding behaviors; Fire - disasters; Food; Functional disorder; Goals; Health; Human; Indium; Lead; Lesion; Localized; Locomotion; Measures; Medial; Mediating; Methods; Modeling; Motivation; Neural Inhibition; Neurons; Nucleus Accumbens; Outcome; Pathology; Pattern; Pharmaceutical Preparations; Pharmacology; Play; Property; Rate; Rattus; Relative (related person); Rewards; Role; Site; Stimulus; Sucrose; Techniques; Testing; Time; Videotape; Water; addiction; approach behavior; awake; drug seeking behavior; early onset; experience; feeding; neural circuit; neuromechanism; novel; reinforcer; relating to nervous system; research study; response

DESCRIPTION (provided by applicant): Our long-term goal is to understand function in brain circuits which regulate reward-seeking and feeding behaviors. Brain circuits which regulate these behaviors are also implicated in the control of defensive responding elicited by threat or aversive stimuli; however, the manner in which these circuits coordinate competing appetitive and defensive behaviors is not understood. Pharmacological inhibition of neural firing in the medial shell region of the nucleus accumbens (NAcc) has been shown to dramatically elevate food intake in satiated animals and to increase reward-seeking behaviors; conversely, increases in neural firing in this region suppress food intake in hungry animals. The neural firing patterns which underlie these behavioral effects are poorly understood. Electrophysiological experiments in behaving animals have demonstrated that the predominant pattern of neural firing encountered in recordings from the NAcc is of an inhibition of neural firing occurring prior to and during feeding behavior. In the proposed experiments, we will test the hypothesis that NAcc neurons possessing this firing pattern play an important role in the normal control of appetitive and feeding behavior, and that inhibition of firing in these neurons underlies the behavioral effects of pharmacological inhibition of firing in the NAcc shell. In Specific Aim 1, we will examine the core/shell distribution of this firing pattern to determine if it is predominantly localized to the NAcc shell. In Specific Aim 2 we will determine if this firing pattern is correlated with appetitive behaviors. Specifically, we will measure and compare firing in this class of neurons during reward seeking to determine 1) if inhibition onset is synchronous with the onset of goal-directed locomotor approach behaviors and 2) if inhibition of neural firing occurs specifically during goal-directed locomotor and operant behaviors. In Specific Aim 3 we will test the response properties of these NAcc neurons during presentation of an aversive cue, to test the hypothesis that aversive stimuli increase firing rate in these neurons, with the behavioral effect of suppressing appetitive/feeding behaviors when threat stimuli arise. These studies are relevant to human health because they will aid in elucidating function in neural circuits that underlie initiation of goal-directed behavior, and importantly, in identifying neural mechanisms mediating suppression of reward-seeking behaviors. Neural dysfunction in disorders of motivation such as addiction is characterized by an inability to inhibit drug-seeking behaviors despite the damaging consequences of continued drug use. The experiments outlined will aid in understanding function in neural circuits importantly implicated in addiction. Addiction is characterized by an inability to suppress drug-seeking despite the devastating negative consequences of continued drug use. Understanding brain circuits which regulate natural reward-seeking behaviors is an important step in understanding neural changes underlying addiction. The proposed experiments will elucidate function in brain circuits importantly implicated in initiating reward-seeking behavior.

描述（由申请人提供）：我们的长期目标是了解调节寻求奖励和喂养行为的大脑电路的功能。调节这些行为的大脑回路也涉及控制防御性反应的控制，这是由于威胁或厌恶刺激引起的。但是，这些电路协调竞争性和防御行为的方式尚不清楚。已显示，伏隔核（NACC）中内侧壳区域的神经点火的药理抑制已显示可显着提高饱腹动物中的食物摄入量，并增加寻求奖励的行为；相反，该区域的神经点火增加抑制了饥饿动物的食物摄入量。这些行为效应的基础的神经射击模式知之甚少。在行为动物中进行的电生理实验表明，NACC记录中遇到的神经射击的主要模式是对喂养行为之前和期间发生的神经发射的抑制。在拟议的实验中，我们将检验以下假设：具有这种发射模式的NaCC神经元在正常控制食用和喂养行为中起着重要作用，并且这些神经元中对发射的抑制是NACC壳中药物学抑制的行为影响。在特定的目标1中，我们将检查该点火模式的核心/壳分布，以确定它是否主要定位于NACC壳。在特定目标2中，我们将确定这种射击模式是否与食欲行为相关。具体而言，我们将在奖励期间测量和比较这类神经元中的射击，以确定1）抑制作用是否与目标指导的运动运动行为同步，并且2）如果抑制神经射击，则在靶向的运动型运动和操作行为期间会特别发生神经射击。在特定目标3中，我们将在呈现厌恶提示期间测试这些NaCC神经元的反应特性，以检验以下假设：厌恶刺激会增加这些神经元的火灾速率，并在威胁刺激时抑制食欲/进食行为的行为效应。这些研究与人类健康有关，因为它们将有助于阐明启动目标指导行为的神经回路的功能，并重要地在识别介导抑制寻求奖励行为的神经机制方面。动机疾病（例如成瘾）的神经功能障碍的特征是无法抑制寻求药物的行为，尽管持续使用毒品的危害后果。概述的实验将有助于理解与成瘾相关的神经回路的功能。成瘾的特征是尽管持续使用毒品造成了毁灭性的负面影响，但仍无法抑制寻求药物。了解调节自然奖励行为的大脑回路是理解成瘾基础神经变化的重要步骤。提出的实验将阐明在启动寻求奖励行为的大脑电路中的功能。