Synaptic Dynamics of the Feed-forward Inhibitory Circuitry Gating Mechanical Allodynia in Mice
Autor: | Xiaolan He, Shibin Du, Yan Lu, Nan Gu, Peng Liu, Zhenhua Jiang, Xiao Zhang, Lu Qi, Chen Liang, Qun Wang |
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Rok vydání: | 2020 |
Předmět: |
Male
Stimulation Mice Transgenic Gating Inhibitory postsynaptic potential 03 medical and health sciences Mice Random Allocation 0302 clinical medicine Organ Culture Techniques Pregnancy Ganglia Spinal medicine Animals Protein kinase C 030304 developmental biology 0303 health sciences business.industry Neural Inhibition Nerve injury Bicuculline Cell biology Mice Inbred C57BL Anesthesiology and Pain Medicine Allodynia Hyperalgesia Synapses Female Sciatic nerve medicine.symptom Nerve Net business 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Anesthesiology. 132(5) |
ISSN: | 1528-1175 |
Popis: | Background The authors’ previous studies have found that spinal protein kinase C γ expressing neurons are involved in the feed-forward inhibitory circuit gating mechanical allodynia in the superficial dorsal horn. The authors hypothesize that nerve injury enhances the excitability of spinal protein kinase C γ expressing interneurons due to disinhibition of the feed-forward inhibitory circuit, and enables Aβ primary inputs to activate spinal protein kinase C γ expressing interneurons. Methods Prkcg-P2A-tdTomato mice were constructed using the clustered regularly interspaced short palindromic repeats and clustered regularly interspaced short palindromic repeats-associated nuclease 9 technology, and were used to analyze the electrophysiologic properties of spinal protein kinase C γ expressing neurons in both normal conditions and pathologic conditions induced by chronic constriction injury of the sciatic nerve. Patch-clamp whole cell recordings were used to identify the nature of the dynamic synaptic drive to protein kinase C γ expressing neurons. Results Aβ fiber stimulation evoked a biphasic synaptic response in 42% (31 of 73) of protein kinase C γ expressing neurons. The inhibitory components of the biphasic synaptic response were blocked by both strychnine and bicuculline in 57% (16 of 28) of neurons. Toll-like receptor 5 immunoreactive fibers made close contact with protein kinase C γ expressing neurons. After nerve injury, the percentage of neurons double-labeled for c-fos and Prkcg-P2A-tdTomato in animals walking on a rotarod was significantly higher than that in the nerve injury animals (4.1% vs. 9.9%, 22 of 539 vs. 54 of 548,P < 0.001). Aβ fiber stimulation evoked burst action potentials in 25.8% (8 of 31) of protein kinase C γ expressing neurons in control animals, while the proportion increased to 51.1% (23 of 45) in nerve injury animals (P = 0.027). Conclusions The Prkcg-P2A-tdTomato mice the authors constructed provide a useful tool for further analysis on how the spinal allodynia gate works. The current study indicated that nerve injury enhanced the excitability of spinal protein kinase C γ expressing interneurons due to disinhibition of the feed-forward inhibitory circuit, and enabled Aβ primary inputs to activate spinal protein kinase C γ expressing interneurons. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New |
Databáze: | OpenAIRE |
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