Multimodal Sensory Integration in Orbitofrontal Cortex during Natural Reward Seeking

项目摘要 对奖励的感知高度依赖于确切的奖励寻求背景。这表明，离散 情境的元素可以通过多感官整合直接影响奖励的主观价值， 重要的是，更高价值的奖励可以推动更多的奖励学习和寻求。了解 多模态刺激如何调节奖励主观价值并告知奖励学习是不完整的， 决定这些刺激在大脑中是如何以及在哪里被处理的。眶额皮质（OFC） 先前已经报道了对独特的味道/气味对共同响应，但是这种稳定性是不确定的。 随着时间的推移和直接连接到初级感觉输入的代表性尚未评估。的目的 这个项目是为了确定如何多感官整合的离散环境刺激配对与主要 奖励会影响寻求奖励的联想学习，并获得对多感觉的功能性理解。 在单细胞水平上在OFC中编码。首先用自然奖励回路来解决这个问题是至关重要的 以获得对成瘾期间不适应的基本神经生物学的全面理解。因此，该项目 将利用味觉奖励和环境嗅觉刺激，这是一种以前被 据报道在人类研究中提高了促味剂的价值。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， 奖励寻求此外，我预测，同样的OFC合奏将被持续激活， 多感官，奖励相关的刺激，这种活动利用直接输入从初级感觉皮层。 在这个项目中，目标1将解决如何多模式整合环境刺激（气味）与主要的 奖励（tastant）影响在一天的学习任务中寻求奖励的学习率，同时评估 奖励值使用一种新的适口性度量。目标2将解决稳定性和与主设备的直接连接 使用同时双光子的用于多模态味觉/嗅觉刺激的OFC中的集合的感觉输入 钙成像和光遗传学。总之，这些目标将确定整合的贡献 离散的环境刺激与线索奖励，以驱动学习的奖励寻求，并提供一个 了解可能导致这种现象的神经回路。该项目的成果将奠定一个至关重要的 为未来的项目奠定基础，以评估整合离散环境和奖励的电路如何 在成瘾过程中，刺激被吸收，以使成瘾和复吸过程中的药物寻求永久化。

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.