Characterisation of rebound depolarisation in mice deep dorsal horn neurons in vitro

Abstract

Spinal dorsal horn neurons constitute the first relay for pain processing and participate in the processing of other sensory, motor and autonomic information. At the cellular level, intrinsic excitability is a factor contributing to network function. In turn, excitability is set by the array of ionic conductance expressed by neurons. Here, we set out to characterise rebound depolarisation following hyperpolarisation, a feature frequently described in dorsal horn neurons but never addressed in depth. To this end, an in vitro preparation of the spinal cord from mice pups was used combined with whole-cell recordings in current and voltage clamp modes. Results show the expression of H- and/or T-type currents in a significant proportion of dorsal horn neurons. The expression of these currents determines the presence of rebound behaviour at the end of hyperpolarising pulses. T-type calcium currents were associated to high-amplitude rebounds usually involving high-frequency action potential firing. H-currents were associated to low-amplitude rebounds less prone to elicit firing or firing at lower frequencies. For a large proportion of neurons expressing both currents, the H-current constitutes a mechanism to ensure a faster response after hyperpolarisations, adjusting the latency of the rebound firing. We conclude that rebound depolarisation and firing are intrinsic factors to many dorsal horn neurons that may constitute a mechanism to integrate somatosensory information in the spinal cord, allowing for a rapid switch from inhibited-to-excited states.

Lidocaine Inhibits HCN Currents in Rat Spinal Substantia Gelatinosa Neurons

“… 52 , 53 The latency of rebound depolarization is determined by I h . 54 In our study, lidocaine not only delayed the latency of rebound depolarization but also reduced the number of rebound spikes, in line with previous studies on thalamocortical neurons. 5 , 17 , 55 These data further indicate that lidocaine can suppress the excitability of SG neurons by blocking HCN channels.…”

Excitability of Rat Superficial Dorsal Horn Neurons Following a Neonatal Immune Challenge

“…In the remaining neurons, we observed three types of responses upon release from hyperpolarization: an extended hyperpolarization where it took some time (>200 ms) for membrane potential to return to RMP; and a rebound depolarization which occurred with or without AP discharge. These responses upon release from hyperpolarization have been previously associated with calcium subthreshold currents ( 30 ).…”

Origin and classification of spontaneous discharges in mouse superficial dorsal horn neurons

“…In agreement with previous reports 15 , our present results suggest that the I h is expressed in many dorsal horn neurons although the current density is significantly larger in neurons that fire spontaneous action potentials. The current may be particularly large in a subset of spinal neurons with regular activity 26 . The present experiments show that ZD7288 applied at 10 µM during a prolonged time produces an almost complete blockade of the current recorded in voltage clamp mode as well as the sag and rebound depolarisation seen during hyperpolarising current pulses in current clamp recordings.…”

“…Depolarising and hyperpolarising intracellular current pulses of 500 ms were applied to study the firing pattern and the passive electrical properties of neurons like input resistance and cell capacitance 15 . The presence of depolarising voltage sag and rebound depolarisations was also studied 26 .…”