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

Publication ,  Journal Article
Joffe, ME; Maksymetz, J; Luschinger, JR; Dogra, S; Ferranti, AS; Luessen, DJ; Gallinger, IM; Xiang, Z; Branthwaite, H; Melugin, PR; Shields, BC ...
Published in: Neuron
March 2022

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.

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Published In

Neuron

DOI

EISSN

1097-4199

ISSN

0896-6273

Publication Date

March 2022

Volume

110

Issue

6

Start / End Page

1068 / 1083.e5

Related Subject Headings

  • Synapses
  • Somatostatin
  • Prefrontal Cortex
  • Neuronal Plasticity
  • Neurology & Neurosurgery
  • Mice
  • Long-Term Potentiation
  • Interneurons
  • Animals
  • 5202 Biological psychology
 

Citation

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Joffe, M. E., Maksymetz, J., Luschinger, J. R., Dogra, S., Ferranti, A. S., Luessen, D. J., … Conn, P. J. (2022). Acute restraint stress redirects prefrontal cortex circuit function through mGlu5 receptor plasticity on somatostatin-expressing interneurons. Neuron, 110(6), 1068-1083.e5. https://doi.org/10.1016/j.neuron.2021.12.027
Joffe, Max E., James Maksymetz, Joseph R. Luschinger, Shalini Dogra, Anthony S. Ferranti, Deborah J. Luessen, Isabel M. Gallinger, et al. “Acute restraint stress redirects prefrontal cortex circuit function through mGlu5 receptor plasticity on somatostatin-expressing interneurons.Neuron 110, no. 6 (March 2022): 1068-1083.e5. https://doi.org/10.1016/j.neuron.2021.12.027.
Joffe ME, Maksymetz J, Luschinger JR, Dogra S, Ferranti AS, Luessen DJ, et al. Acute restraint stress redirects prefrontal cortex circuit function through mGlu5 receptor plasticity on somatostatin-expressing interneurons. Neuron. 2022 Mar;110(6):1068-1083.e5.
Joffe, Max E., et al. “Acute restraint stress redirects prefrontal cortex circuit function through mGlu5 receptor plasticity on somatostatin-expressing interneurons.Neuron, vol. 110, no. 6, Mar. 2022, pp. 1068-1083.e5. Epmc, doi:10.1016/j.neuron.2021.12.027.
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. Acute restraint stress redirects prefrontal cortex circuit function through mGlu5 receptor plasticity on somatostatin-expressing interneurons. Neuron. 2022 Mar;110(6):1068-1083.e5.
Journal cover image

Published In

Neuron

DOI

EISSN

1097-4199

ISSN

0896-6273

Publication Date

March 2022

Volume

110

Issue

6

Start / End Page

1068 / 1083.e5

Related Subject Headings

  • Synapses
  • Somatostatin
  • Prefrontal Cortex
  • Neuronal Plasticity
  • Neurology & Neurosurgery
  • Mice
  • Long-Term Potentiation
  • Interneurons
  • Animals
  • 5202 Biological psychology