Subtype 5 metabotropic glutamate receptors (mGlu₅) are known to play an important role in regulating cognitive, social and valence systems. However, it remains largely unknown at which circuits and neuronal types mGlu₅ act to influence these behavioral domains. Altered tissue- or cell-specific expression or function of mGlu₅ has been proposed to contribute to the exacerbation of neuropsychiatric disorders. Here, we examined how these receptors regulate the activity of somatostatin-expressing (SST+) neurons, as well as their influence on behavior and brain rhythmic activity. Loss of mGlu₅ in SST+ neurons elicited excitatory synaptic dysfunction in a region and sex-specific manner together with a range of emotional imbalances including diminished social novelty preference, reduced anxiety-like behavior and decreased freezing during retrieval of fear memories. In addition, the absence of mGlu₅ in SST+ neurons during fear processing impaired theta frequency oscillatory activity in the medial prefrontal cortex and ventral hippocampus. These findings reveal a critical role of mGlu₅ in controlling SST+ neurons excitability necessary for regulating negative emotional states.

已知亚型 5 代谢型谷氨酸受体 (mGlu _{5 ) 在调节认知、社会和效价系统中发挥重要作用。然而，mGlu 5}在哪些回路和神经元类型中影响这些行为领域仍然很大程度上未知。 mGlu ₅的组织或细胞特异性表达或功能的改变被认为会导致神经精神疾病的恶化。在这里，我们研究了这些受体如何调节表达生长抑素（SST+）神经元的活动，以及它们对行为和大脑节律活动的影响。 SST+ 神经元中 mGlu ₅的缺失会引起某个区域和性别特异性的兴奋性突触功能障碍，以及一系列情绪失衡，包括社交新奇偏好减少、焦虑样行为减少以及恐惧记忆检索过程中的冻结减少。此外，在恐惧处理过程中，SST+ 神经元中 mGlu ₅的缺失会损害内侧前额叶皮层和腹侧海马的 θ 频率振荡活动。这些发现揭示了 mGlu ₅在控制 SST+ 神经元兴奋性方面的关键作用，而兴奋性是调节负面情绪状态所必需的。