A modelling study of locomotion‐induced hyperpolarization of voltage threshold in cat lumbar motoneurones

Abstract

During fictive locomotion in adult cat, spinal motoneurones exhibit changes in intrinsic membrane properties during the transition from the resting to the locomotor state. These state-dependent changes include a reduction in the post-spike afterhyperpolarization (AHP) (Brownstone et al. 1992;Schmidt, 1994) and a change in the relation between intracellular current injection and firing frequency (Brownstone et al. 1992;Fedirchuk et al. 1998). Krawitz et al. (2001) recently described another state-dependent change in motoneurone excitability accompanying the transition to locomotion: a hyperpolarization of the voltage threshold (Vth) for action potential (AP) initiation. While the mechanisms for this enhancement of motoneuronal excitability are unknown, the authors postulated that this effect might be mediated by neuromodulators released during locomotor activity (Krawitz et al. 2001).The primary aim of the present study was to determine possible ionic mechanisms that might account for hyperpolarization of Vth in cat lumbar motoneurones during fictive locomotion. To this end, we built three models corresponding to three biophysical types of motoneurones (S, slow; FR, fast, fatigue resistant; FF, fast fatigable) with properties resembling those of real motoneurones recorded in vivo. The models were built with five compartments (axon, initial segment, soma, proximal dendrite and distal dendrite) of unequal size that approximated a simplified anatomical structure of real motoneurones. The passive membrane properties of the models were based on data from cat spinal motoneurones. Parameters for the 10 active conductances included in the models were taken primarily from the literature for mammalian spinal motoneurones. The ten conductances During fictive locomotion the excitability of adult cat lumbar motoneurones is increased by a reduction (a mean hyperpolarization of ~6.0 mV) of voltage threshold (Vth) for action potential (AP) initiation that is accompanied by only small changes in AP height and width. Further examination of the experimental data in the present study confirms that Vth lowering is present to a similar degree in both the hyperpolarized and depolarized portions of the locomotor step cycle. This indicates that Vth reduction is a modulation of motoneurone membrane currents throughout the locomotor state rather than being related to the phasic synaptic input within the locomotor cycle. Potential ionic mechanisms of this locomotor-state-dependent increase in excitability were examined using three fivecompartment models of the motoneurone innervating slow, fast fatigue resistant and fast fatigable muscle fibres. Passive and active membrane conductances were set to produce input resistance, rheobase, afterhyperpolarization (AHP) and membrane time constant values similar to those measured in adult cat motoneurones in non-locomoting conditions. The parameters of 10 membrane conductances were then individually altered in an attempt to replicate the hyperpolarization of Vth that occurs in decerebrate cats during...

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