Emergence of valence coding in the ventral striatum

腹侧纹状体价编码的出现

基本信息

批准号：
10577864
负责人：
VENKATESH N MURTHY
金额：
$ 49.14万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10577864
关键词：
Address Air Animals Area Association Learning Aversive Stimulus Axon Behavior Behavioral Paradigm Binge Eating Brain Categories Code Cues Decision Making Disease Dopamine Drug Addiction Event Fiber Foundations Goals Heterogeneity Hot Spot Image Learning Motivation Mus Nature Neurons Neurosciences Odors Olfactory Cortex Olfactory tubercle Outcome Photometry Physiology Play Population Predictive Value Process Punishment Research Response to stimulus physiology Rewards Rodent Role Sensory Shapes Signal Transduction Site Stimulus Testing Training Ventral Striatum Ventral Tegmental Area addiction calcium indicator cell type cocaine self-administration efficacious treatment flexibility maladaptive behavior microendoscopy nerve supply neural neural circuit neuromechanism neurotransmission novel olfactory bulb optogenetics piriform cortex public health relevance sensory input sensory stimulus

项目摘要

Summary The ability to learn associations between a specific sensory stimulus and an outcome such as re- ward or punishment is a basic requirement for flexible behaviors. Malfunctions of this associative process may underlie various disorders such as drug addiction and binge eating. Rodents can learn novel stimulus-response associations after only a few repetitions, but the circuits that are modified during learning are largely unknown. The olfactory tubercle (OT), a part of the ventral stri- atum, is located at the interface between sensory and reward centers, receiving strong olfactory sensory input as well as dopaminergic innervation from the ventral tegmental area (VTA). It has been implicated in reward and is a recognized “hot spot” for cocaine self-administration. These ob- servations suggest that the OT is the site of heterosynaptic plasticity to establish valence represen- tation associated with odors. The PIs have developed a behavioral paradigm in mice that allows rapid and flexible association of arbitrary odor cues with reward or aversion. Using this behavior, they have found evidence for an explicit representation of reward in the OT. In this project, the PIs will test the hypothesis that neural activity in the OT is modified during learning to reflect the va- lence of stimuli, and that dopaminergic signals from the VTA play a key role in this learning. Aim 1: To determine whether OT neurons signal explicit (odor-independent) valence signals after learn- ing. Mice will be trained to learn the arbitrarily assigned valence of a panel of odors and record spiking activity using tetrodes from the OT in behaving animals. The hypothesis tested is that there is an explicit valence representation in the activity of OT neurons and this representation emerges rapidly when novel odor associations are learned. Aim 2: To determine how reward and aversion are represented in the OT. The PIs will use aversive and rewarding stimuli to ask whether OT neu- rons represent true valence signals, or if they signal motivational salience. The hypothesis is that OT activity will be modulated in opposite directions for rewarding and aversive cues, signaling ex- plicit valence, with potential heterogeneity across OT cell types and subregions. Aim 3: To deter- mine whether dopaminergic axons targeting OT carry valence related signals that evolve during learning. The PIs will use fiber photometry and microendoscopy to record valence-related activity of dopaminergic axons in the OT and optogenetics to stimulate these axons in behaving mice. The hypothesis is that the OT receives dopamine inputs that represent value prediction errors that can shape the valence-related activity of OT neurons. The research proposed has broad relevance for neuroscience because it will shed light on how reward-predicting signals are learnt and represent- ed in the brain, which could help devise treatments in abnormal conditions such as addiction.

概括学习特定感官刺激与结果（例如重新定义）之间关联的能力监护或惩罚是灵活行为的基本要求。这个过程可能是各种疾病的根源，例如吸毒成瘾和啮齿类动物的暴食。仅经过几次重复就可以学习新的刺激-反应关联，但是这些电路嗅结节（OT）是腹侧条纹的一部分，在学习过程中发生的改变在很大程度上是未知的。 atum，位于感觉和奖励中心之间的界面，接收强烈的嗅觉感觉输入以及来自腹侧被盖区（VTA）的多巴胺能神经支配。与奖励有关，是公认的可卡因自我给药的“热点”。观察表明 OT 是异质突触可塑性的位点，以建立价代表 PI 已经在小鼠中开发了一种行为范式，允许使用这种行为，将任意气味线索与奖励或厌恶快速而灵活地联系起来。他们发现了在 OT 中明确表示奖励的证据，即 PI。将检验以下假设：OT 中的神经活动在学习过程中被修改以反映 va- 刺激的存在，来自 VTA 的多巴胺能信号在这一学习中发挥着关键作用：确定 OT 神经元在学习后是否发出明确的（与气味无关的）价信号小鼠将被训练学习一组气味的任意指定价并记录。使用来自 OT 的四极管在行为动物中进行尖峰活动所测试的假设是存在的。是 OT 神经元活动中的明确价态表示，并且这种表示出现目标 2：确定奖赏和厌恶的方式。 PI 会使用厌恶性和奖励性刺激来询问 OT 是否是神经性的。 rons 代表真实的价信号，或者它们是否代表动机显着性。假设是这样的。 OT 活动将向相反的方向调节，以获得奖励和厌恶的线索，发出前明确的效价，在 OT 细胞类型和亚区域之间具有潜在的异质性。目标 3：阻止探究针对 OT 的多巴胺能轴突是否携带在过程中进化的价相关信号 PI 将使用光纤光度测定法和显微内窥镜来记录与价相关的活动。 OT 中的多巴胺能轴突和光遗传学刺激行为小鼠的这些轴突。假设是 OT 接收代表价值预测错误的多巴胺输入，这些错误可以塑造 OT 神经元的价态相关活动。神经科学，因为它将揭示奖励预测信号是如何学习和表示的—— 大脑中的信号，这可以帮助设计针对成瘾等异常情况的治疗方法。