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

John Cheriyan, Patrick Sheets

Research output: Contribution to journalArticle

16 Citations (Scopus)

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

Fingerprint

Periaqueductal Gray
Neuralgia
Prefrontal Cortex
Constriction
Neurons
Wounds and Injuries
Chronic Pain
Glutamic Acid
Pain
Patch-Clamp Techniques
Sciatic Nerve
Mesencephalon
Analgesics
Lasers
Brain

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Altered excitability and local connectivity of mPFC-PAG neurons in a mouse model of neuropathic pain. / Cheriyan, John; Sheets, Patrick.

In: Journal of Neuroscience, Vol. 38, No. 20, 16.05.2018, p. 4829-4839.

Research output: Contribution to journalArticle

@article{a81b9b6094b34a308342d942ec64c059,
title = "Altered excitability and local connectivity of mPFC-PAG neurons in a mouse model of neuropathic pain",
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.",
keywords = "Circuit mapping, Mouse, MPFC, Nerve injury, Neuropathic pain, PAG",
author = "John Cheriyan and Patrick Sheets",
year = "2018",
month = "5",
day = "16",
doi = "10.1523/JNEUROSCI.2731-17.2018",
language = "English (US)",
volume = "38",
pages = "4829--4839",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "20",

}

TY - JOUR

T1 - Altered excitability and local connectivity of mPFC-PAG neurons in a mouse model of neuropathic pain

AU - Cheriyan, John

AU - Sheets, Patrick

PY - 2018/5/16

Y1 - 2018/5/16

N2 - 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.

AB - 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.

KW - Circuit mapping

KW - Mouse

KW - MPFC

KW - Nerve injury

KW - Neuropathic pain

KW - PAG

UR - http://www.scopus.com/inward/record.url?scp=85049306424&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049306424&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.2731-17.2018

DO - 10.1523/JNEUROSCI.2731-17.2018

M3 - Article

C2 - 29695413

AN - SCOPUS:85049306424

VL - 38

SP - 4829

EP - 4839

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 20

ER -