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

Cell Reports
Andrea F Jones, Patrick L Sheets

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.

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Citations

Nov 27, 2020·Nature Communications·Li SunShumin Duan
Dec 15, 2020·Journal of Neuroscience Research·Blake A KimmeyGregory Corder
Jun 3, 2021·Biomedicines·Myeong Seong BakSun Kwang Kim
Jun 16, 2021·Nature Reviews. Neuroscience·Linette Liqi Tan, Rohini Kuner

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