Multimodal Sensory Integration in Orbitofrontal Cortex during Natural Reward Seeking

项目总结 对奖赏的感知高度依赖于确切的奖赏寻求背景。这表明，离散的 背景因素可能通过多感官整合直接影响奖励主观价值，即 这一点很重要，因为更高价值的奖励可以推动学习和寻求更多的奖励。一种对 多通道刺激如何调节奖赏主观价值并告知奖赏学习 确定这些刺激在大脑中的处理方式和位置。眶前叶皮质(OFC)中的群体 此前有报道称，它们对独特的味觉/嗅觉对有共同反应，但这种稳定性 随时间推移的表征以及与初级感觉输入的直接联系尚未得到评估。目的 该项目旨在确定离散环境刺激的多感官整合如何与初级刺激配对 奖赏影响寻求奖赏的联想学习并获得对多感官的功能性理解 在单信元级的OFC中进行编码。首先用自然奖赏回路来解决这个问题是至关重要的 对成瘾期间不适应的基本神经生物学有一个全面的了解。因此，这个项目 将利用味觉奖励和环境嗅觉刺激，这是以前的组合 据报道，在人体研究中提高了味觉价值。我假设环境的多感官整合 刺激和奖励会增加奖励的主观价值，加快联想学习的速度，并提高 寻求回报。此外，我预测同样的OFC合奏将被一致地激活以 多感官、奖赏相关刺激，这一活动利用初级感觉皮质的直接输入。 在这个项目中，目标1将解决环境刺激(气味)与主要环境刺激的多模式整合 奖赏(品味)影响单日学习任务中寻求奖赏的学习速度，同时评估 奖励价值使用一种新的适口性指标。目标2将解决稳定性和直接连接到主服务器的问题 利用同时双光子实现多模式味觉/嗅觉刺激的OFC集合的感觉输入 钙成像和光遗传学。这些目标加在一起，将确立整合 离散的环境刺激和线索奖励，以驱动学习寻求奖励，并提供 对可能导致这一现象的神经回路的理解。这项工程的成果将为未来的发展奠定重要的基础 为未来的项目奠定基础，以评估集成离散环境和奖励的电路 在上瘾期间使用刺激物，以在上瘾和复发期间持续寻求毒品。

PROJECT SUMMARY Perception of rewards is highly dependent on the exact reward seeking context. This suggests that discrete elements of the context may directly influence reward subjective value via multisensory integration, which is important because higher-value rewards can drive increased reward learning and seeking. An understanding of how multimodal stimuli modulate reward subjective value and inform reward learning is incomplete without determining how and where these stimuli are processed in the brain. Ensembles in the orbitofrontal cortex (OFC) have been previously reported to be co-responsive to unique taste/smell pairs, but the stability of this representation over time and direct connection to primary sensory input has not been assessed. The purpose of this project is to determine how multisensory integration of discrete environmental stimuli paired with primary rewards impacts associative learning for reward seeking and to gain a functional understanding of multisensory encoding in the OFC at the single cell level. It is vital to first address this question with natural reward circuitry to gain a full understanding of the basic neurobiology that is maladapted during addiction. As such, this project will utilize a tastant reward and an environmental olfactory stimulus, a combination that has previously been reported to enhance tastant value in human studies. I hypothesize that multisensory integration of environmental stimuli and rewards will increase reward subjective value, expedite the rate of associative learning, and enhance reward seeking. Additionally, I predict that the same OFC ensembles will be consistently activated to multisensory, reward-relevant stimuli and that this activity utilizes direct input from primary sensory cortices. In this project, Aim 1 will address how the multimodal integration of environmental stimuli (odor) with a primary reward (tastant) impacts the rate of learning for reward seeking in a single-day learning task, while assessing reward value using a novel palatability metric. Aim 2 will address the stability and direct connection to primary sensory input of ensembles in the OFC for the multimodal taste/smell stimulus using simultaneous two-photon calcium imaging and optogenetics. Together, these aims will establish the contribution of the integration of discrete environmental stimuli with cued reward to drive learning for reward seeking and provide an understanding of the neural circuitry that may underlie this phenomenon. The results of this project will lay a vital groundwork for future projects to assess how the circuitry that integrates discrete environmental and reward stimuli is coopted during addiction to perpetuate drug seeking during addiction and relapse.