Neonatal tissue injury reduces the intrinsic excitability of adult mouse superficial dorsal horn neurons

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• 作者：J. Li ; M.L. Baccei
• 关键词：aCSF ; artificial cerebrospinal fluid ; ANOVA ; analysis of variance ; AP ; action potential ; Cm ; membrane capacitance ; Erev ; reversal potential ; eGFP ; enhanced GFP ; Gad-GFP ; glutamic acid decarboxylase-green fluorescent protein ; HEPES ; N-(2-hydroxyethyl)piperazine-N&prime ; -2-ethanesulfonic acid ; IF ; instantaneous firing frequency ; Kir ; inward-rectifying K+ ; Rm ; membrane resistance ; SDH ; superficial dorsal horn ; Vm ; membrane potential ; Vrest ; resting membrane potential
• 刊名：Neuroscience
• 出版年：3 January, 2014
• 年：2014
• 卷：256
• 期：Complete
• 页码：392-402
• 全文大小：724 K

文摘

Tissue damage during the neonatal period evokes long-lasting changes in nociceptive processing within the adult spinal cord which contribute to persistent alterations in pain sensitivity. However, it remains unclear if the observed modifications in neuronal activity within the mature superficial dorsal horn (SDH) following early injury reflect shifts in the intrinsic membrane properties of these cells. Therefore, the present study was undertaken to identify the effects of neonatal surgical injury on the intrinsic excitability of both GABAergic and presumed glutamatergic neurons within lamina II of the adult SDH using in vitro patch clamp recordings from spinal cord slices prepared from glutamic acid decarboxylase-green fluorescent protein (Gad-GFP) mice. The results demonstrate that hindpaw surgical incision at postnatal day (P) 3 altered the passive membrane properties of both Gad-GFP and adjacent, non-GFP neurons in the mature SDH, as evidenced by decreased membrane resistance and more negative resting potentials in comparison to na茂ve littermate controls. This was accompanied by a reduction in the prevalence of spontaneous activity within the GABAergic population. Both Gad-GFP and non-GFP neurons displayed a significant elevation in rheobase and decreased instantaneous firing frequency after incision, suggesting that early tissue damage lowers the intrinsic membrane excitability of adult SDH neurons. Isolation of inward-rectifying K⁺ (K_ir) currents revealed that neonatal incision significantly increased K_ir conductance near physiological membrane potentials in GABAergic, but not glutamatergic, lamina II neurons. Overall, these findings suggest that neonatal tissue injury causes a long-term dampening of intrinsic firing across the general population of lamina II interneurons, but the underlying ionic mechanisms may be cell-type specific.