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

Abstract

Meaningful body movements depend on the interplay between synaptic inputs to motoneurons and their intrinsic properties. Injury and disease often alter either or both of these factors and cause motoneuron and movement dysfunction. 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.

Fig. 1

The dendritic persistent inward current (PIC) amplified and prolonged synaptic input in a low-threshold, type S motoneuron. (A) At a hyperpolarized holding potential (−90 mV; green trace), synaptic input produced a steady current with a sharp onset and offset. At a depolarized holding potential (~−55 mV; red trace), the PIC is activated and amplifies and prolongs the same input. Baseline holding currents are removed to allow the traces to be superimposed. (B) The difference between the currents in A reflects the net PIC contribution (C) In current clamp, the same input produces a steady excitatory post-synaptic potential (EPSP) when the cell is hyperpolarized (~−90 mV; green trace). At a more depolarized level (−70 mV; red trace) [offset removed], the input evokes repetitive firing and then slower self-sustained firing when the input is removed. Data are from Lee and Heckman (1996). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Block diagram illustrating the flow of events following SCI. The differential effects of monoamines on the dorsal and ventral horns are indicated. The site of action and nature of effect of the various drugs used for the management of spasticity after SCI are illustrated. Red color indicates a positive action, i.e., increase, whereas a blue color indicates a negative action, i.e., reduction. Figure adapted from Elbasiouny et al. (2009). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

A timeline summary showing the progression of events in the various animal models of ALS. (See above-mentioned references for further information.)