Evaluating the function and activity dynamics of thalamic inputs for reward seeking and consumption

评估丘脑输入的功能和活动动态以寻求奖励和消费

基本信息

批准号：
9051064
负责人：
James M Otis
金额：
$ 5.61万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
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 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9051064
关键词：
Accelerometer Animals Appetitive Behavior Area Automobile Driving Behavior Behavioral Biological Neural Networks Brain CAV2 gene Calcium Complex Consumption Contrast Media Cues Data Disease Dopamine Drug Addiction Electric Stimulation Etiology Fiber Glutamates Goals Hypothalamic structure Image Impairment Knowledge Lateral Learning Medial Midbrain structure Midline Thalamic Nuclei Mission Modeling Motivation Mus Neurobiology Neurons Nucleus Accumbens Obesity Output Pharmaceutical Preparations Phase Physiological Prefrontal Cortex Presynaptic Terminals Prosencephalon Public Health Publishing Research Rewards Signal Transduction Stimulus Synaptic plasticity System Thalamic structure The Sun Virus Work addiction awake base behavioral impairment cell type driving behavior extracellular feeding hindbrain in vivo insight mesolimbic system motivated behavior neural circuit neuropsychiatric disorder optogenetics prevent public health relevance relating to nervous system research study retrograde transport tool

项目摘要

DESCRIPTION (provided by applicant): Function and natural activity dynamics of thalamic inputs for reward seeking. Compulsive reward seeking and taking are hallmarks of addiction, although the precise neural circuits that orchestrate these basic motivational states remain unclear. This is in part due to a lack of experimental feasibility, as it has been difficult to conrol and monitor the activity of cell-type specific neurons in vivo. For example, the paraventricular thalamus (PVT) is a midline thalamic nucleus that interfaces with motivational circuits, is a critical regulator of feeding, and is necessary for reinstatement in several models of drug seeking. Despite this, how PVT neurons function within a broader circuit to regulate these motivational states is unknown. Thus, the objective of this project is to use contemporary tools to study the precise neurocircuitry that engages PVT for the control of reward seeking. Here I propose to identify the function and natural activity dynamics of two primary PVT inputs, particularly from the lateral hypothalamus (LH) and prelimbic cortex (PLc), for the control of reward seeking. The function of PVT inputs for reward seeking will be evaluated with inhibitory optogenetics during distinct phases of a cue-induced reward-seeking task (Aim 1). Furthermore, the natural activity dynamics of these projection-specific neurons will be visualized during reward seeking and taking through deep-brain calcium imaging in awake, freely moving mice (Aim 2). Based on my preliminary data and published work by my sponsor and others, I hypothesize that PVT-projecting LH neurons will be active and necessary for reward seeking and consumption. In contrast, based on my preliminary data and my previously published work, I hypothesize that PVT-projecting PLc neurons will be active and necessary specifically for cue-driven reward seeking, but not reward seeking and consumption in general. These data would suggest that the PVT acts to integrate distinct signals regarding motivational drive (LH) and environmental stimuli (PLc) to regulate reward-seeking behavior. Regardless of the results, these experiments will identify the function and natural activity dynamics of LH-PVT and PLc-PVT neurons for the control of reward seeking and taking.

描述（由申请人提供）：丘脑输入寻求奖励的功能和自然活动动态是成瘾的标志，尽管协调这些基本动机状态的精确神经回路仍不清楚。缺乏实验可行性，因为很难在体内控制和监测细胞类型特异性神经元的活动，例如，室旁丘脑（PVT）是中线丘脑核。尽管如此，PVT 神经元如何在更广泛的回路中发挥作用来调节这些动机状态尚不清楚。项目的目的是使用现代工具来研究参与 PVT 控制奖励寻求的精确神经回路，我建议确定两个主要 PVT 输入的功能和自然活动动态，特别是来自外侧下丘脑 (LH) 和前边缘皮层 (PLc)，用于控制奖励寻求在提示诱导的奖励寻求任务的不同阶段，将使用抑制光遗传学来评估 PVT 输入的功能（目标 1）。这些投射特异性神经元的一部分将在奖励寻求过程中被可视化，并通过对清醒、自由活动的小鼠进行深脑钙成像（目标 2），我着迷于这一点。相比之下，根据我的初步数据和我之前发表的工作，PVT 投射的 LH 神经元对于奖励寻求和消耗将是活跃的和必需的，我发现 PVT 投射的 PLc 神经元对于线索驱动的奖励寻求将是活跃的和必需的。，但不是一般的奖励寻求和消费。这些数据表明，PVT 对有关动机驱动 (LH) 和环境刺激 (PLc) 的不同信号起作用，以调节奖励寻求行为。功能和自然活动LH-PVT 和 PLc-PVT 神经元的动力学用于控制奖励寻求和获取。