State‐dependent hyperpolarization of voltage threshold enhances motoneurone excitability during fictive locomotion in the cat

Abstract

Electrical stimulation of the brainstem in paralysed decerebrate cats evokes a centrally generated pattern of motor output (fictive locomotion) that has many of the characteristics of overground locomotion in adult quadripedal mammals (see Rossignol, 1996). During fictive locomotion, motoneurones innervating limb muscles receive alternating excitatory and inhibitory synaptic currents from the central pattern generator (CPG) for locomotion (Jordan, 1983). These result in the rhythmic fluctuations of membrane potential (locomotor drive potentials, LDPs) that underlie the patterned activation of motoneurones during locomotion. The transformation of rhythmic excitatory drive into trains of action potentials is governed by the passive and active membrane properties of motoneurones. It is now known that some of these properties are altered during locomotion. For example, the post-spike afterhyperpolarization (AHP) is reduced in motoneurones during fictive locomotion (Brownstone et al. 1992;Schmidt, 1994) and there is the appearance of a voltagedependent excitatory current (Brownstone et al. 1994). This voltage-dependent excitation results in non-linear responses of motoneurones to depolarizing currents, which may facilitate the recruitment of motoneurones, or augment motoneuronal output evoked by reflex or central excitation (Brownstone et al. 1994;McCrea et al. 1997;Bennett et al. 1998). These changes in motoneurone membrane properties result in increased motoneuronal firing in response to intracellular current injection during fictive locomotion (Brownstone et al. 1992;. The fictive locomotor state thus appears to include processes that increase the excitability of hindlimb motoneurones.The membrane potential at which action potentials are initiated in response to sufficient depolarizing currents (the voltage threshold, V th ) is not a fixed value in motoneurones. For example, V th tends to be higher (more depolarized) in higher rheobase motoneurones (Gustafsson & Pinter, 1984) 1. Experiments were conducted on decerebrate adult cats to examine the effect of brainstemevoked fictive locomotion on the threshold voltage (V th ) at which action potentials were initiated in hindlimb motoneurones. Measurements of the voltage threshold of the first spike evoked by intracellular injection of depolarizing ramp currents or square pulses were compared during control and fictive locomotor conditions. The sample of motoneurones included flexor and extensor motoneurones, and motoneurones with low and high rheobase currents.2. In all 38 motoneurones examined, action potentials were initiated at more hyperpolarized membrane potentials during fictive locomotion than in control conditions (mean hyperpolarization _8.0 ± 5.5 mV; range _1.8 to _26.6 mV). Hyperpolarization of V th occurred immediately at the onset of fictive locomotion and recovered in seconds (typically < 60 s) following the termination of locomotor activity.3. The V th of spikes occurring spontaneously without intracellular current injection was also reduced during loc...

Beginning at the end: Repetitive firing properties in the final common pathway

“…Further analysis of repetitive firing during MLR-induced fictive locomotion demonstrated that the voltage threshold for initiation of APs is hyperpolarized compared to resting conditions (Krawitz et al, 2001). In a subsequent modeling study, this hyperpolarization was readily accounted for by modulation of the fast inactivating sodium current (Dai et al, 1998).…”

“…Once alternating locomotor activity began, however, the firing rate increased to the pre-adapted frequency, indicating a "reversal" of late SFA. If late SFA is mediated by a long time constant of inactivation of fast sodium channels (Section 7), then the Krawitz et al (1996) data, together with the data indicating hyperpolarization of voltage threshold (Krawitz et al, 2001), may indicate modulation of these channels during locomotor activity. Finally, if late SFA is related to fatigue (Kernell and Monster, 1982a;Gandevia, 2001), then modulating (reducing) this property during locomotion may enable the animal to sustain locomotor activity for lengthy periods of time.…”

Contribution of intrinsic motoneuron properties to discharge hysteresis and its estimation based on paired motor unit recordings: a simulation study

“…However, our simulations indicate these other effects would not counteract the effects of changes in PIC amplitude on discharge hysteresis and ⌬F values. For example, neuromodulators have been shown to lower spike threshold (e.g., Fedirchuk and Dai 2004;Krawitz et al 2001). Our simulations indicate that raising spike threshold through increases in accommodation reduces ⌬F values; thus lowering spike threshold should enhance the effects of neuromodulatory drive on ⌬F.…”

Long-Term Plasticity of Ipsilesional Medial Vestibular Nucleus Neurons After Unilateral Labyrinthectomy

“…For each neuron, an average of the spike shape and following inter-spike interval profile was obtained by averaging successive spontaneous spikes taken either at the resting membrane potential or while the cell was slightly depolarized (for the few neurons that were silent at rest). The spikes (mean number of ϳ120) were synchronized to their thresholds, taken at the point on the rising phase of the action potential where the slope of the potential trace reached an arbitrary threshold of 10 V/s (Krawitz et al 2001). The averaged spike shape was used to determine the amplitude of the afterhyperpolarization (AHP) and the width of the spike (taken at threshold).…”