Persistent inward currents in spinal motoneurons: Important for normal function but potentially harmful after spinal cord injury and in amyotrophic lateral sclerosis

Clin Neurophysiol, 2010 · DOI: 10.1016/j.clinph.2009.12.041 · Published: October 1, 2010

Simple Explanation

Meaningful body movements depend on the interplay between synaptic inputs to motoneurons and their intrinsic properties. The ability of the motoneuronal membrane to generate persistent inward currents (PICs) is especially potent in setting the intrinsic excitability of motoneurons and can drastically change the motoneuron output to a given input. In this article, we review the role of PICs in modulating the excitability of spinal motoneurons during health, and their contribution to motoneuron excitability after spinal cord injury (SCI) and in amyotrophic lateral sclerosis (ALS) leading to exaggerated long-lasting reflexes and muscle spasms, and contributing to neuronal degeneration, respectively.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Level 5: Review Article

Key Findings

1
The motoneuronal PIC recovers after chronic SCI, restoring motoneuronal excitability and contributing to long-lasting reflexes and muscle spasms.
2
In ALS, altered motoneuron excitability and increased PIC amplitude may play a key role in subsequent pathology and motoneuron death.
3
Spasticity in humans involves similar Na+ and Ca2+ ionic mechanisms to those found in animal models.

Research Summary

Spinal motoneurons are the final neural output of the central nervous system (CNS) through which motor commands to peripheral muscles are communicated. The level of the monoaminergic drive from the brainstem to spinal cord varies between motor behaviors and is proportional to the level of required motor activity. After injury or a neurological disease, pathological changes in these mechanisms occur that contribute to the resulting motor deficit.

Practical Implications

Targeted drug therapies for spasticity

Drugs that target 5-HT2 and NE α1 receptors (facilitating motoneuron PICs) in combination with agonists of 5-HT1b/d and NE α2 receptors (inhibiting sensory processing in the dorsal horn) may be optimal for controlling spasms.

Electrical field modulation for spasticity

Application of direct current (DC) and alternating current (AC) electrical fields across the spinal cord may reduce motoneuronal hyperexcitability via modulation of the dendritic PIC.

Rehabilitation interventions for SCI

Rehabilitation interventions targeting PICs or other likely mechanisms are expected to be effective in reducing the severity of spasticity.

Study Limitations

1
The pathophysiology of spasticity is still unclear, and the reemergence of PICs after SCI appears to be one of the contributing factors to the manifestation of spasticity.
2
More work is needed to elucidate the nature of alterations in ALS motoneuron excitability in the various genetic models of ALS using various protocols of current injection and in preparations having intact motoneuron dendrites.
3
Studies looking specifically at the development of both the Na+ and Ca2+ PIC and motoneuron morphology are needed to distinguish the primary versus secondary changes in ALS.

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