Spinal Cord Injury Significantly Alters the Properties of Reticulospinal Neurons: I. Biophysical Properties, Firing Patterns, Excitability, and Synaptic Inputs.

Ryan A Hough,Jessica A Benes,Timothee Pale,Andrew D Mcclellan

doi:10.3390/cells10081921

Abstract

Following spinal cord injury (SCI) for larval lampreys, descending axons of reticulospinal (RS) neurons regenerate, and locomotor function gradually recovers. In the present study, the electrophysiological properties of uninjured (left)-injured (right) pairs of large, identified RS neurons were compared following rostral, right spinal cord hemi-transections (HTs). First, changes in firing patterns of injured RS neurons began in as little as 2–3 days following injury, these changes were maximal at ~2–3 weeks (wks), and by 12–16 wks normal firing patterns were restored for the majority of neurons. Second, at ~2–3 wks following spinal cord HTs, injured RS neurons displayed several significant changes in properties compared to uninjured neurons: (a) more hyperpolarized VREST; (b) longer membrane time constant and larger membrane capacitance; (c) increased voltage and current thresholds for action potentials (APs); (d) larger amplitudes and durations for APs; (e) higher slope for the repolarizing phase of APs; (f) virtual absence of some afterpotential components, including the slow afterhyperpolarization (sAHP); (g) altered, injury-type firing patterns; and (h) reduced average and peak firing (spiking) frequencies during applied depolarizing currents. These altered properties, referred to as the “injury phenotype”, reduced excitability and spiking frequencies of injured RS neurons compared to uninjured neurons. Third, artificially injecting a current to add a sAHP waveform following APs for injured neurons or removing the sAHP following APs for uninjured neurons did not convert these neurons to normal firing patterns or injury-type firing patterns, respectively. Fourth, trigeminal sensory-evoked synaptic responses recorded from uninjured and injured pairs of RS neurons were not significantly different. Following SCI, injured lamprey RS neurons displayed several dramatic changes in their biophysical properties that are expected to reduce calcium influx and provide supportive intracellular conditions for axonal regeneration.

Highlights

The pattern of rhythmic muscle burst activity during locomotor behavior is produced by central pattern generators (CPGs), which consist of neuronal oscillators that are distributed along the spinal cord and coupled by a coordinating system [1]
At 4–8 wk recovery times, there was an increase in the percentage of RS neurons displaying smooth repetitive firing and a decrease in the percentage exhibiting injury-type firing patterns (Table 1, Figure 2(A5,A6))
Except for M3, which is the poorest axonal regenerator among Müller cells [18] and accounted for only ~5% of neurons sampled at 12–16 wk recovery times, the percentages of the other different RS neurons that were recorded from at different recovery times were roughly comparable (Table A1 in Appendix A; see Discussion)

Summary

Introduction

The pattern of rhythmic muscle burst activity during locomotor behavior is produced by central pattern generators (CPGs), which consist of neuronal oscillators that are distributed along the spinal cord and coupled by a coordinating system [1]. Locomotion is initiated, maintained, and regulated by a brain command system, the output of which consists of reticulospinal (RS) neurons whose descending axons activate spinal CPGs [1,3]. A threshold level of activity for RS neurons, further increases in the activity of these neurons is correlated with an increase in the frequency of rhythmic spinal locomotor activity [4]. Increases in the intensity of experimental stimulation in medullary reticular nuclei increase the frequency of spinal locomotor activity and locomotor movements [5,6,7].

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Conclusion