Woo Elizabeth, Datta Dibyadeep, Arnsten Amy F T
Department of Neuroscience, Yale University School of Medicine, New Haven, CT, United States.
Front Neuroanat. 2022 Apr 4;16:849937. doi: 10.3389/fnana.2022.849937. eCollection 2022.
Metabotropic glutamate receptors type 3 (mGlu3, encoded by ) are increasingly related to cognitive functioning, including the working memory operations of the prefrontal cortex (PFC). In rhesus monkeys, mGlu3 are most commonly expressed on glia (36%), but are also very prominent on layer III dendritic spines (23%) in the dorsolateral PFC (dlPFC) where they enhance working memory-related neuronal firing. In contrast, mGlu2 are predominately presynaptic in layer III of macaque dlPFC, indicating a pre- vs. post-synaptic dissociation by receptor subtype. The current study examined the cellular and subcellular localizations of mGlu3 in the rat prelimbic medial PFC (PL mPFC), a region needed for spatial working memory performance in rodents. Multiple label immunofluorescence demonstrated mGlu3 expression in neurons and astrocytes, with rare labeling in microglia. Immunoelectron microscopy of layers III and V found that the predominant location for mGlu3 was on axons (layer III: 35.9%; layer V: 44.1%), with labeling especially prominent within the intervaricose segments distant from axon terminals. mGlu3 were also found on glia (likely astrocytes), throughout the glial membrane (layer III: 28.2%; layer V: 29.5%). Importantly, mGlu3 could be seen on dendritic spines, especially in layer III (layer III: 15.6%; layer V: 8.2%), with minor labeling on dendrites. These data show that there are some similarities between mGlu3 expression in rat PL mPFC and macaque dlPFC, but the spine expression enriches and differentiates in the more recently evolved primate dlPFC.
代谢型谷氨酸受体3（mGlu3，由 编码）与认知功能的关系日益密切，包括前额叶皮质（PFC）的工作记忆操作。在恒河猴中，mGlu3最常见于神经胶质细胞（36%），但在背外侧前额叶皮质（dlPFC）的III层树突棘上也非常突出（23%），在那里它们增强了与工作记忆相关的神经元放电。相比之下，mGlu2在猕猴dlPFC的III层中主要位于突触前，这表明受体亚型存在突触前与突触后解离的情况。本研究检测了mGlu3在大鼠前边缘内侧前额叶皮质（PL mPFC）中的细胞和亚细胞定位，该区域是啮齿动物空间工作记忆表现所必需的。多重标记免疫荧光显示mGlu3在神经元和星形胶质细胞中表达，在小胶质细胞中的标记很少。对III层和V层的免疫电子显微镜检查发现，mGlu3的主要位置在轴突上（III层：35.9%；V层：44.1%），在远离轴突终末的曲张段内标记尤为突出。在整个神经胶质细胞膜上也发现了mGlu3在神经胶质细胞（可能是星形胶质细胞）上（III层：28.2%；V层：29.5%）。重要的是，在树突棘上可以看到mGlu3，尤其是在III层（III层：15.6%；V层：8.2%），在树突上有少量标记。这些数据表明，大鼠PL mPFC和猕猴dlPFC中mGlu3的表达存在一些相似之处，但在进化程度更高的灵长类动物dlPFC中，树突棘表达更加丰富且有所不同。
