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

Abstract Subtype 5 metabotropic glutamate receptors (mGlu 5 ) 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 mGlu 5 act to influence these behavioral domains. Altered tissue- or cell-sp...

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Published in:Molecular psychiatry 2024-04
Main Authors: Ramos-Prats, Arnau, Matulewicz, Pawel, Edenhofer, Marie-Luise, Wang, Kai-Yi, Yeh, Chia-Wei, Fajardo-Serrano, Ana, Kress, Michaela, Kummer, Kai, Lien, Cheng-Chang, Ferraguti, Francesco
Format: Article
Language:English
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Summary:Abstract Subtype 5 metabotropic glutamate receptors (mGlu 5 ) 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 mGlu 5 act to influence these behavioral domains. Altered tissue- or cell-specific expression or function of mGlu 5 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 mGlu 5 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 mGlu 5 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 mGlu 5 in controlling SST+ neurons excitability necessary for regulating negative emotional states.
ISSN:1359-4184
1476-5578
DOI:10.1038/s41380-024-02541-5