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