Loss of mGlu₅ receptors in somatostatin-expressing neurons alters negative emotional states

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.