Acute restraint stress redirects prefrontal cortex circuit function through mGlu 5 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 mGlu receptor activation facilitates long-term potentiation at...

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Published inNeuron (Cambridge, Mass.) Vol. 110; no. 6; p. 1068
Main Authors Joffe, Max E, Maksymetz, James, Luschinger, Joseph R, Dogra, Shalini, Ferranti, Anthony S, Luessen, Deborah J, Gallinger, Isabel M, Xiang, Zixiu, Branthwaite, Hannah, Melugin, Patrick R, Williford, Kellie M, Centanni, Samuel W, Shields, Brenda C, Lindsley, Craig W, Calipari, Erin S, Siciliano, Cody A, Niswender, Colleen M, Tadross, Michael R, Winder, Danny G, Conn, P Jeffrey
Format Journal Article
LanguageEnglish
Published United States 16.03.2022
Subjects
Animals
Interneurons - physiology
Long-Term Potentiation
Mice
Neuronal Plasticity - physiology
Prefrontal Cortex - physiology
Somatostatin - metabolism
Synapses - physiology
DART
metabotropic glutamate receptor
working memory
antidepressant
motivation
optogenetics
GABA
GPCR
Ca(2+)-permeable AMPA receptor
GluA2-lacking AMPA receptor
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Summary: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.
ISSN:1097-4199