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bioRxiv · 10.1101/2022.09.15.508019

Parvalbumin protein controls inhibitory tone in the spinal cord

Qiu, H.·Miraucourt, L.·Petitjean, H.·Davidova, A.·Levesque-Damphousse, P.·Estall, J. L.·Sharif-Naeini, R.
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Abstract

The nervous system processes sensory information by relying on the precise coordination of neuronal networks and their specific synaptic firing patterns. In the spinal cord, disturbances to the firing pattern of the tonic firing parvalbumin (PV)-expressing inhibitory interneuron (PV neurons) disrupt the ability of the dorsal horn to integrate touch information and may result in pathological phenotypes. The parvalbumin protein (PVp) is a calcium (Ca2+)-binding protein that buffers the accumulation of Ca2+ following a train of action potential to allow for tonic firing. Here, we find that peripheral nerve injury causes a decrease in PVp expression in PV neurons and makes them transition from tonic to adaptive firing. We also show that reducing the expression of PVp causes otherwise healthy adult mice to develop mechanical allodynia and causes their PV neurons to lose their high frequency firing pattern. We show that this frequency adaptation is mediated by activation of SK channels on PV neurons. Further, we show their tonic firing can be partially restored after nerve injury by selectively inhibiting the SK2 channels of PV neurons. We also reveal that a decrease in the transcriptional coactivator, PGC-1, causes decrease PVp expression and the development of mechanical allodynia. By preventing the decrease in PVp expression before nerve injury, we were able to protect mice from developing mechanical allodynia. Our results indicate an essential role for PVp-mediated calcium buffering in PV neuron firing activity and the development of mechanical allodynia after nerve injury.

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Qiu, H., Miraucourt, L., Petitjean, H., Davidova, A., Levesque-Damphousse, P., Estall, J. L., Sharif-Naeini, R.. 2022-09-17. Parvalbumin protein controls inhibitory tone in the spinal cord. https://doi.org/10.1101/2022.09.15.508019

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