Systems-level interactions underlying valence coding in olfaction

描述(由申请人提供)：嗅觉不仅提供关于气味质量的信息(即气味是什么)，而且还提供关于气味的情感含义的信息给观察者：除了潜在的麝香或水果味外，气味可能是愉快的或令人厌恶的，部分取决于观察者过去的经验。人类受试者的大脑成像研究表明，嗅觉皮质--由于其与涉及学习、记忆和情绪的神经系统的连接--在代表气味价态方面发挥着核心作用。然而，气味质量编码向与行为相关的气味价态编码转化的细胞过程尚不清楚。本提议将电生理记录与气味价态的行为测量相结合，以探测嗅皮层神经元小群对一组已知价态的气味的反应。第一组实验旨在测试价相关神经放电模式如何以及何时出现在嗅皮层。基于我们实验室以前对味觉系统中价编码的研究工作，具体的假设是气味质量和价都在单一嗅觉皮质神经元的动态反应模式中编码。从这些实验中获得的结果的有效性将通过改变气味的价态来测试--将其与甜味配对，并观察之前确定的价态相关的反应模式是否会相应地改变。最后，通过结合嗅皮层气味反应的电生理记录和一系列候选区域的光遗传失活，将确定与价相关的放电模式的来源。在现有文献和大量初步数据的指导下，味觉皮质、杏仁核和眶前叶皮质的失活被假设为影响嗅皮层中价相关的放电模式。 这些实验的结果将影响我们对情绪、记忆和各种临床症状的理解，这些症状会影响我们对有价刺激的感知(最明显的是自闭症)。

DESCRIPTION (provided by applicant): Smell perception serves to provide information not only about odor quality (i.e., what the odor is), but also about the emotional meaning of the odor to an observer: besides being potentially musky or fruity, odors can be experienced as pleasant or aversive, dependent in part on past experience of the observer. Brain imaging research in human subjects has demonstrated that olfactory cortex-owing to its connectivity to neural systems involved in learning, memory and emotion-plays a central role in representing odor valence. However, the cellular processes underlying the transformation of odor quality coding to behaviorally-relevant odor valence coding is as of yet unknown. The present proposal combines electrophysiological recordings with behavioral measures of odor valence to probe responses of small ensembles of olfactory cortical neurons to a set of odors with a known range of valences. A first set of experiments is designed to test how and when valence-related neural firing patterns appear in olfactory cortex. Based on previous work from our lab investigating valence coding in the taste system, the specific hypothesis is that odor quality and valence are both encoded in the dynamic response patterns of single olfactory cortex neurons. The validity of the results obtained from these experiments will then be tested by changing the valence of an odor-pairing it with sweet taste, and observing whether the previously- identified valence-related response patterns change accordingly. Finally, the source of valence-related firing patterns will be determined by combining optogenetic inactivation of a range of candidate regions with electrophysiological recordings of odor responses in olfactory cortex. Guided by the extant literature as well as a wealth of preliminary data, inactivation of taste cortex, the amygdala and orbitofrontal cortex is hypothesized to affect valence-related firing patterns in olfactory cortex. The results obtained from these experiments will influence our understanding of emotion, memory, and a variety of clinical syndromes known to affect perception of valenced stimuli (most notably autism).