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

Authors

Joffe ME Max E , Maksymetz J James , Luschinger JR Joseph R , Dogra S Shalini , Ferranti AS Anthony S , Luessen DJ Deborah J , Gallinger IM Isabel M , Xiang Z Zixiu , Branthwaite H Hannah , Melugin PR Patrick R , Williford KM Kellie M , Centanni SW Samuel W , Shields BC Brenda C , Lindsley CW Craig W , Calipari ES Erin S , Siciliano CA Cody A , Niswender CM Colleen M , Tadross MR Michael R , Winder DG Danny G , Conn PJ P Jeffrey .
Neuron. 2022 01 18; 110(6).
1068-1083.e5

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 mGlu 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 mGlu 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 mGlu receptor knockout mice revealed that mGlu 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.