Altered excitability and local connectivity of mPFC-PAG neurons in a mouse model of neuropathic pain

John Cheriyan, Patrick L. Sheets

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The medial prefrontal cortex (mPFC) plays a major role in both sensory and affective aspects of pain. There is extensive evidence that chronic pain produces functional changes within the mPFC. However, our understanding of local circuit changes to defined subpopula-tions of mPFC neurons in chronic pain models remains unclear. A major subpopulation of mPFC neurons project to the periaqueductal gray (PAG), which is a key midbrain structure involved in endogenous pain suppression and facilitation. Here, we used laser scanning photostimulation of caged glutamate to map cortical circuits of retrogradely labeled cortico-PAG (CP) neurons in layer 5 (L5) of mPFC in brain slices prepared from male mice having undergone chronic constriction injury (CCI) of the sciatic nerve. Whole-cell recordings revealed a significant reduction in excitability for L5 CP neurons contralateral to CCI in the prelimbic (PL), but not infralimbic (IL), region of mPFC. Circuit mappingshowedthat excitatoryinputs toL5CPneurons inbothPLandILaroseprimarilyfromlayer 2/3(L2/3) andwere significantly reduced in CCI mice. Glutamate stimulation of L2/3 and L5 elicited inhibitory inputs to CP neurons in both PL and IL, but only L2/3 input was significantly reduced in CP neurons of CCI mice. We also observed significant reduction in excitability and L2/3 inhibitory input to CP neurons ipsilateral to CCI. These results demonstrating region and laminar specific changes to mPFC-PAG neurons suggest that a unilateral CCI bilaterally alters cortical circuits upstream of the endogenous analgesic network, which may contribute to persistence of chronic pain.

Original languageEnglish (US)
Pages (from-to)4829-4839
Number of pages11
JournalJournal of Neuroscience
Volume38
Issue number20
DOIs
StatePublished - May 16 2018

Keywords

  • Circuit mapping
  • MPFC
  • Mouse
  • Nerve injury
  • Neuropathic pain
  • PAG

ASJC Scopus subject areas

  • Neuroscience(all)

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