Postinhibitory excitation in motoneurons can be facilitated by hyperpolarization-activated inward currents: A simulation study

PLoS Comput Biol. 2024 Jan 19;20(1):e1011487. doi: 10.1371/journal.pcbi.1011487. eCollection 2024 Jan.

Abstract

Postinhibitory excitation is a transient overshoot of a neuron's baseline firing rate following an inhibitory stimulus and can be observed in vivo in human motoneurons. However, the biophysical origin of this phenomenon is still unknown and both reflex pathways and intrinsic motoneuron properties have been proposed. We hypothesized that postinhibitory excitation in motoneurons can be facilitated by hyperpolarization-activated inward currents (h-currents). Using an electrical circuit model, we investigated how h-currents can modulate the postinhibitory response of motoneurons. Further, we analyzed the spike trains of human motor units from the tibialis anterior muscle during reciprocal inhibition. The simulations revealed that the activation of h-currents by an inhibitory postsynaptic potential can cause a short-term increase in a motoneuron's firing probability. This result suggests that the neuron can be excited by an inhibitory stimulus. In detail, the modulation of the firing probability depends on the time delay between the inhibitory stimulus and the previous action potential. Further, the postinhibitory excitation's strength correlates with the inhibitory stimulus's amplitude and is negatively correlated with the baseline firing rate as well as the level of input noise. Hallmarks of h-current activity, as identified from the modeling study, were found in 50% of the human motor units that showed postinhibitory excitation. This study suggests that h-currents can facilitate postinhibitory excitation and act as a modulatory system to increase motoneuron excitability after a strong inhibition.

MeSH terms

  • Action Potentials
  • Biophysics
  • Humans
  • Motor Neurons* / physiology
  • Muscle, Skeletal / physiology
  • Synaptic Transmission* / physiology

Grants and funding

This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, SPP 2311 (465243391) to LS) and the European Research Council (ERC-AdG “qMOTION” (Grant agreement ID: 101055186) to TK; Consolidator Grant INcEPTION (contract no. 101045605) to FN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.