Emergence of valence coding in the ventral striatum

摘要 学习特定感觉刺激和结果之间的联系的能力，例如 监护或处罚是灵活行为的基本要求。该联轴器的故障 过程可能是各种疾病的基础，如吸毒成瘾和暴饮暴食。啮齿动物可以 只需重复几次就能学习新的刺激-反应联系，但 在学习过程中被修改的情况在很大程度上是未知的。嗅结节(OT)是腹侧束的一部分。 ATOM位于感觉和奖赏中枢的交界处，接受强烈的嗅觉 感觉输入以及腹侧被盖区(VTA)的多巴胺能神经支配。它有 与报酬有牵连，是公认的可卡因自我管理的“热点”。这些Ob- 结果表明，OT是异交可塑性建立价代表的位置。 与气味有关的符号。PI已经在小鼠身上开发了一种行为范式，可以 快速而灵活地将任意气味提示与奖励或厌恶联系起来。使用此行为， 他们已经找到了在加时赛中明确表示奖励的证据。在这个项目中，PI 将检验这样一种假设，即在学习过程中，OT中的神经活动被修改，以反映出 来自VTA的多巴胺能信号在这种学习中起着关键作用。目标1： 为了确定OT神经元在学习后是否发出明确的(气味无关)价信号- 英。小鼠将接受训练，学习一组气味的任意分配价位并记录 在表现良好的动物身上使用来自OT的四酮类物质进行刺激性活动。经过检验的假设是， 是OT神经元活动中的显式价表示，这种表示出现了 当学习到新的气味联系时，会迅速产生。目标2：确定奖励和厌恶如何 在加时赛中都有代表。PI将使用厌恶和奖励的刺激来询问OT Neu- Ron代表真实的价态信号，或者如果它们发出激励显著的信号。假设是这样的 OT活性将被以相反的方向调节，以获得奖励和厌恶的暗示，发出信号。 诱生价，在OT细胞类型和亚区之间具有潜在的异质性。目标3：威慑- 靶向催产素的多巴胺能轴突是否携带价相关信号 学习。PI将使用纤维光度测定法和显微内窥镜来记录价相关活动 OT和光遗传学中的多巴胺能轴突的研究，以刺激行为小鼠的这些轴突。这个 假设OT接收表示值预测误差的多巴胺输入，该值预测误差 塑造催产素神经元的价相关活动。提出的研究具有广泛的关联性 因为它将阐明奖励预测信号是如何学习和代表的-- 大脑中的ED，这可以帮助设计出治疗上瘾等异常情况的方法。

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.