Sex-Specific Disruption of Distinct mPFC Inhibitory Neurons in Spared-Nerve Injury Model of Neuropathic Pain

Andrea F. Jones, Patrick L. Sheets

Research output: Contribution to journalArticlepeer-review

Abstract

The medial prefrontal cortex (mPFC) modulates a range of behaviors, including responses to noxious stimuli. While various pain modalities alter mPFC function, our understanding of changes to specific cell types underlying pain-induced mPFC dysfunction remains incomplete. Proper activity of cortical GABAergic interneurons is essential for normal circuit function. We find that nerve injury increases excitability of layer 5 parvalbumin-expressing neurons in the prelimbic (PL) region of the mPFC from male, but not female, mice. Conversely, nerve injury dampens excitability in somatostatin-expressing neurons in layer 2/3 of the PL region; however, effects are differential between males and females. Nerve injury slightly increases the frequency of spontaneous excitatory post-synaptic currents (sEPSCs) in layer 5 parvalbumin-expressing neurons in males but reduces frequency of sEPSCs in layer 2/3 somatostatin-expressing neurons in females. Our findings provide key insight into how nerve injury drives maladaptive and sex-specific alterations to GABAergic circuits in cortical regions implicated in chronic pain.

Original languageEnglish (US)
Article number107729
JournalCell Reports
Volume31
Issue number10
DOIs
StatePublished - Jun 9 2020

Keywords

  • GABAergic neurons
  • PVIN
  • SOM
  • medial prefrontal cortex
  • nerve injury
  • pain
  • parvalbumin
  • sex-specific
  • slice electrophysiology
  • somatostatin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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