Acute restraint stress redirects prefrontal cortex circuit function through mGlu5 receptor plasticity on somatostatin-expressing interneurons.
Journal Article (Journal Article)
Inhibitory interneurons orchestrate prefrontal cortex (PFC) activity, but we have a limited understanding of the molecular and experience-dependent mechanisms that regulate synaptic plasticity across PFC microcircuits. We discovered that mGlu5 receptor activation facilitates long-term potentiation at synapses from the basolateral amygdala (BLA) onto somatostatin-expressing interneurons (SST-INs) in mice. This plasticity appeared to be recruited during acute restraint stress, which induced intracellular calcium mobilization within SST-INs and rapidly potentiated postsynaptic strength onto SST-INs. Restraint stress and mGlu5 receptor activation each augmented BLA recruitment of SST-IN phasic feedforward inhibition, shunting information from other excitatory inputs, including the mediodorsal thalamus. Finally, studies using cell-type-specific mGlu5 receptor knockout mice revealed that mGlu5 receptor function in SST-expressing cells is necessary for restraint stress-induced changes to PFC physiology and related behaviors. These findings provide new insights into interneuron-specific synaptic plasticity mechanisms and suggest that SST-IN microcircuits may be promising targets for treating stress-induced psychiatric diseases.
Full Text
Duke Authors
Cited Authors
- Joffe, ME; Maksymetz, J; Luschinger, JR; Dogra, S; Ferranti, AS; Luessen, DJ; Gallinger, IM; Xiang, Z; Branthwaite, H; Melugin, PR; Williford, KM; Centanni, SW; Shields, BC; Lindsley, CW; Calipari, ES; Siciliano, CA; Niswender, CM; Tadross, MR; Winder, DG; Conn, PJ
Published Date
- March 2022
Published In
Volume / Issue
- 110 / 6
Start / End Page
- 1068 - 1083.e5
PubMed ID
- 35045338
Pubmed Central ID
- PMC8930582
Electronic International Standard Serial Number (EISSN)
- 1097-4199
International Standard Serial Number (ISSN)
- 0896-6273
Digital Object Identifier (DOI)
- 10.1016/j.neuron.2021.12.027
Language
- eng