Abstract
Activity-dependent changes in the properties of the motor system underlie the necessary adjustments in its responsiveness on the basis of the environmental and developmental demands of the organism. Although plastic changes in the properties of the spinal cord have historically been neglected because of the archaic belief that the spinal cord is constituted by a hardwired network that simply relays information to muscles, plenty of evidence has been accumulated showing that synapses impinging on spinal motoneurons undergo short- and long-term plasticity. In the brain, brief changes in the activity level of the network have been shown to be paralleled by changes in the intrinsic excitability of the neurons and are suggested to either reinforce or stabilize the changes at the synaptic level. However, rapid activity-dependent changes in the intrinsic properties of spinal motoneurons have never been reported. In this study, we show that in neonatal mice the intrinsic excitability of spinal motoneurons is depressed after relatively brief but sustained changes in the spinal cord network activity. Using electrophysiological techniques together with specific pharmacological blockers of KCNQ/Kv7 channels, we demonstrate their involvement in the reduction of the intrinsic excitability of spinal motoneurons. This action results from an increased M-current, the product of the activation of KCNQ/Kv7 channels, which leads to a hyperpolarization of the resting membrane potential and a decrease in the input resistance of spinal motoneurons. Computer simulations showed that specific up-regulations in KCNQ/Kv7 channels functions lead to a modulation of the intrinsic excitability of spinal motoneurons as observed experimentally. These results indicate that KCNQ/Kv7 channels play a fundamental role in the activity-dependent modulation of the excitability of spinal motoneurons.
Highlights
The potential for long-term plastic changes in the properties of the spinal motor system has long been doubted because of the archaic belief that the spinal cord is constituted of hardwired networks that relay information to muscles [1]
Using a combination of electrophysiological recordings, pharmacological treatments and computational modeling, we demonstrate that a relatively short but sustained increase in spinal network activity enhances the activity of KCNQ/Kv7 channels in spinal MNs leading to a reduction in their intrinsic excitability
After returning the spinal cord slices to the control artificial cerebro-spinal fluid (ACSF), the spontaneous spinal network activity returned to the initial control level (2.78 ± 0.45 × 103 spikes/minute, n = 19; P = 1; Fig 1B), demonstrating that the increase in the extracellular K+ concentration can be effective in sustainably but reversibly enhancing the spinal network activity for a prolonged period of time
Summary
The potential for long-term plastic changes in the properties of the spinal motor system has long been doubted because of the archaic belief that the spinal cord is constituted of hardwired networks that relay information to muscles [1]. Brief changes in the activity level of the network, such as those necessary to trigger short and long-term synaptic plasticity, have been shown to be paralleled by changes in the neuronal intrinsic excitability, and are mainly suggested to reinforce the changes at the synaptic level. Several investigations have illustrated that the intrinsic excitability of MNs is modulated in the long term after physical training [11], operant conditioning [12], weight bearing [13], as well as after chronic changes in the spinal cord activity [14,15,16]. Since the output of MNs depends on the interaction between the synaptic strength of the connections impinging on them and their intrinsic excitability, understanding the full impact of plastic changes in spinal MNs requires identifying the extent that their intrinsic excitability undergoes relatively rapidly-induced plastic changes
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