Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Department of Psychiatry, John Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Semin Cell Dev Biol. 2022 Sep;129:31-39. doi: 10.1016/j.semcdb.2021.03.022. Epub 2021 May 9.
Olfactory dysfunction is manifested in a wide range of neurological and psychiatric diseases, and often emerges prior to the onset of more classical symptoms and signs. From a behavioral perspective, olfactory deficits typically arise in conjunction with impairments of cognition, motivation, memory, and emotion. However, a conceptual framework for explaining the impact of olfactory processing on higher brain functions in health and disease remains lacking. Here we aim to provide circuit-level insights into this question by synthesizing recent advances in olfactory network connectivity with other cortical brain regions such as the prefrontal cortex. We will focus on social cognition as a representative model for exploring and critically evaluating the relationship between olfactory cortices and higher-order cortical regions in rodent models. Although rodents do not recapitulate all dimensions of human social cognition, they have experimentally accessible neural circuits and well-established behavioral tests for social motivation, memory/recognition, and hierarchy, which can be extrapolated to other species including humans. In particular, the medial prefrontal cortex (mPFC) has been recognized as a key brain region in mediating social cognition in both rodents and humans. This review will highlight the underappreciated connectivity, both anatomical and functional, between the olfactory system and mPFC circuitry, which together provide a neural substrate for olfactory modulation of social cognition and social behaviors. We will provide future perspectives on the functional investigation of the olfactory-mPFC circuit in rodent models and discuss how to translate such animal research to human studies.
嗅觉功能障碍表现为广泛的神经和精神疾病，并且通常在出现更典型的症状和体征之前出现。从行为的角度来看，嗅觉缺陷通常与认知、动机、记忆和情绪的损伤同时出现。然而，用于解释嗅觉处理对健康和疾病中大脑更高功能影响的概念框架仍然缺乏。在这里，我们旨在通过综合嗅觉网络连接的最新进展以及前额叶皮层等其他皮质脑区，为这个问题提供一个回路层面的见解。我们将重点关注社会认知，作为探索和批判性评估嗅觉皮质与啮齿动物模型中更高阶皮质区域之间关系的代表性模型。尽管啮齿动物不能再现人类社会认知的所有维度，但它们具有可实验操作的神经回路和用于社会动机、记忆/识别和等级的既定行为测试，这些可以外推到包括人类在内的其他物种。特别是，内侧前额叶皮层（mPFC）已被认为是介导啮齿动物和人类社会认知的关键脑区。这篇综述将重点介绍嗅觉系统与 mPFC 回路之间被低估的连接，包括解剖和功能连接，它们共同为嗅觉调节社会认知和社会行为提供了神经基础。我们将提供关于在啮齿动物模型中研究嗅觉-mPFC 回路的功能的未来展望，并讨论如何将此类动物研究转化为人类研究。
