Multimodal Sensory Integration in Orbitofrontal Cortex during Natural Reward Seeking

自然奖励寻求过程中眶额皮层的多模态感觉整合

• 批准号: 10383032
• 负责人: Madelyn Hjort
• 金额: $ 4.68万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10383032
• 关键词: Address; Animals; Area; Behavioral; Brain; Calcium; Cells; Consumption; Cues; Desire for food; Drug Addiction; Elements; Environment; Food; Future; Goals; Human; Image; Individual; Learning; Link; Machine Learning; Mus; Neurobiology; Neurons; Odors; Palate; Pathologic; Perception; Pharmaceutical Preparations; Process; Relapse; Reporting; Rewards; Role; Sensory; Site; Smell Perception; Stimulus; Taste Perception; Techniques; Testing; Time; Training; addiction; base; classical conditioning; drug relapse; hippocampal pyramidal neuron; in vivo; indexing; lens; multimodality; multisensory; neural circuit; novel; olfactory stimulus; optogenetics; orofacial; paired stimuli; reward circuitry; sensory cortex; sensory input; sensory integration; sensory stimulus; supervised learning; two-photon

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.

项目摘要 对奖励的感知高度取决于寻求背景的确切奖励。这表明离散 上下文的要素可以通过多感官整合直接影响奖励主观价值，这是 重要的是因为高价值奖励可以推动增加的奖励学习和寻求。对 多模式刺激如何调节奖励主观价值和告知奖励学习是不完整的 确定这些刺激在大脑中的处理方式和地点。 Orbitrontal Cortex（OFC）中的合奏 据报道，以前据报道是对独特的味道/气味对的共同响应，但是稳定性 尚未评估随着时间的推移的表示和直接连接与主要感觉输入的连接。目的 该项目是确定离散环境刺激与主要刺激的多感官整合 奖励会影响奖励寻求奖励并获得对多感官的功能理解的关联学习 在单个单元格级别中编码OFC。首先用自然奖励电路解决这个问题至关重要 为了充分了解成瘾过程中疾病的基本神经生物学。因此，这个项目 将利用味道奖励和环境嗅觉刺激，以前是这种组合 据报道，在人类研究中提高了味道价值。我假设环境的多感官整合 刺激和奖励将增加奖励的主观价值，加快关联学习速度并增强 寻求奖励。此外，我预测，相同的OFC集合将始终激活为 多感官，奖励与奖励刺激，并且这种活动利用了主要感觉皮质的直接输入。 在这个项目中，AIM 1将解决环境刺激（气味）的多模式整合 奖励（品尝者）在评估时会影响单日学习任务中寻求奖励的学习率 使用新颖的可口标准奖励价值。 AIM 2将解决稳定性并直接连接到主要 OFC中合奏的感官输入使用同时进行多模式的口味/气味刺激 钙成像和光遗传学。这些目标将共同确定整合的贡献 离散的环境刺激，并获得奖励，以推动学习奖励寻求奖励并提供 了解可能是这种现象的神经回路。该项目的结果将是至关重要的 未来项目的基础工作，以评估如何整合离散环境和奖励的电路 在成瘾期间，刺激在成瘾和复发期间持续了毒品。