Acute restraint stress redirects prefrontal cortex circuit function through mGlu5 receptor plasticity on somatostatin-expressing interneurons

Max E. Joffe, James Maksymetz, Joseph R. Luschinger, Shalini Dogra, Anthony S. Ferranti, Deborah J. Luessen, Isabel M. Gallinger, Zixiu Xiang, Hannah Branthwaite, Patrick R. Melugin, Kellie M. Williford, Samuel W. Centanni, Brenda C. Shields, Craig W. Lindsley, Erin S. Calipari, Cody A. Siciliano, Colleen M. Niswender, Michael R. Tadross, Danny G. Winder, P. Jeffrey Conn

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1068-1083.e5
JournalNeuron
Volume110
Issue number6
DOIs
StatePublished - 16 Mar 2022
Externally publishedYes

Keywords

  • Ca-permeable AMPA receptor
  • DART
  • GABA
  • GPCR
  • GluA2-lacking AMPA receptor
  • antidepressant
  • metabotropic glutamate receptor
  • motivation
  • optogenetics
  • working memory

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