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

46 Pages Posted: 16 Sep 2019 Sneak Peek Status: Under Review

See all articles by Andrea F. Jones

Andrea F. Jones

Indiana University - Department of Pharmacology and Toxicology

Patrick L. Sheets

Indiana University - Department of Pharmacology and Toxicology

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Abstract

The medial prefrontal cortex (mPFC) modulates a broad 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 GABAergic neurons in the prelimbic (PL) region of mPFC from male, but not female mice. Conversely, nerve injury dampens excitability in somatostatin-expressing GABAergic neurons in layer 2/3 of PL; however, effects are differential between males and females. Nerve injury had minimal effect on spontaneous excitatory post-synaptic currents (sEPSCs) in parvalbumin-expressing neurons, but reduced 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 affective disorders comorbid with chronic pain.

Keywords: Nerve injury, Pain, GABAergic neurons, Parvalbumin, Somatostatin, Slice Electrophysiology, Medial Prefrontal Cortex

Suggested Citation

Jones, Andrea F. and Sheets, Patrick L., Sex-Specific Disruption of Distinct mPFC Inhibitory Neurons in Spared-Nerve Injury Model of Neuropathic Pain (September 12, 2019). CELL-REPORTS-D-19-03440. Available at SSRN: https://ssrn.com/abstract=3452784 or http://dx.doi.org/10.2139/ssrn.3452784
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Andrea F. Jones

Indiana University - Department of Pharmacology and Toxicology

United States

Patrick L. Sheets (Contact Author)

Indiana University - Department of Pharmacology and Toxicology ( email )

United States

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