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