Persistent inward currents in motoneuron dendrites: Implications for motor output

Abstract

The dendrites of motoneurons are not, as once thought, passive conduits for synaptic inputs. Instead they have voltage-dependent channels that provide the capacity to generate a very strong persistent inward current (PIC). The amplitude of the PIC is proportional to the level of neuromodulatory input from the brainstem, which is mediated primarily by the monoamines serotonin and norepinephrine. During normal motor behavior, monoaminergic drive is likely to be moderately strong and the dendritic PIC generates many of the characteristic features of motor unit firing patterns. Most of the PIC activates at or below recruitment threshold and thus motor unit firing patterns exhibit a linear increase just above recruitment. The dendritic PIC allows motor unit derecruitment to occur at a lower input level than recruitment, thus providing sustained tonic firing with little or no synaptic input, especially in low-threshold units. However the dendritic PIC can be readily deactivated by synaptic inhibition. The overall amplification due to the dendritic PIC and other effects of monoamines on motoneurons greatly increases the input-output gain of the motor pool. Thus the brainstem neuromodulatory input provides a mechanism by which the excitability of motoneurons can be varied for different motor behaviors. This control system is lost in spinal cord injury but PICs nonetheless recover near-normal amplitudes in the months following the initial injury. The relationship of these findings to the cause of the spasticity syndrome developing after spinal cord injury is discussed.

Adjustments Differ Among Low-Threshold Motor Units During Intermittent, Isometric Contractions

“…Additionally, slow inactivation of Na ϩ channels and a slowing of the transmembrane Na ϩ -K ϩ pump activity may increase the recruitment threshold (Miles et al 2005;Vilin and Ruben 2001). Because these mechanisms depend on the duration of activation and are particularly relevant in low-threshold motor neurons (Heckman et al 2005), they may have contributed to the differential adjustments in motor unit activity observed in the current study.…”

“…The extrinsic synaptic input needed to recruit a motor neuron may change during a fatiguing contraction. Over short time intervals of motor unit activity, persistent inward currents in the dendrites may reduce the current required from extrinsic synaptic sources to reach recruitment threshold (Fuglevand et al 2006;Gorassini et al 2002;Heckman et al 2005;Nordstrom et al 2007). Longer intervals of motor unit activity, however, may elicit slow inactivation of Ca 2ϩ and Na ϩ persistent inward currents that conversely increase the synaptic current required to reach threshold (Heckman et al 2005).…”

“…Over short time intervals of motor unit activity, persistent inward currents in the dendrites may reduce the current required from extrinsic synaptic sources to reach recruitment threshold (Fuglevand et al 2006;Gorassini et al 2002;Heckman et al 2005;Nordstrom et al 2007). Longer intervals of motor unit activity, however, may elicit slow inactivation of Ca 2ϩ and Na ϩ persistent inward currents that conversely increase the synaptic current required to reach threshold (Heckman et al 2005). Additionally, slow inactivation of Na ϩ channels and a slowing of the transmembrane Na ϩ -K ϩ pump activity may increase the recruitment threshold (Miles et al 2005;Vilin and Ruben 2001).…”

High-frequency submaximal stimulation over muscle evokes centrally generated forces in human upper limb skeletal muscles

“…Despite the simplicity of this method, it has limitations relevant to our paradigm that prevented us from using this technique. There can be saturation in firing frequency of human motor units (13), and there is smaller amplification (36) and larger current leakage in high-threshold motoneurons (compared with low-threshold ones) during plateau potentials (21). Muscle stimulation at 20 Hz presumably elicits ionotropic synaptic currents that are influenced by plateau potentials (21) in spinal motoneurons and interneurones.…”

“…There can be saturation in firing frequency of human motor units (13), and there is smaller amplification (36) and larger current leakage in high-threshold motoneurons (compared with low-threshold ones) during plateau potentials (21). Muscle stimulation at 20 Hz presumably elicits ionotropic synaptic currents that are influenced by plateau potentials (21) in spinal motoneurons and interneurones. The total synaptic current from stretch-related afferents is larger in smaller motoneurons, and, for the same level of stretch-activated input, the firing frequency is larger in small than large motoneurons (36).…”