Anesthetic effects on fictive locomotion in the rat isolated spinal cord

Abstract

General anesthetic mechanisms are poorly understood. Anesthetic immobilizing effects occur in the spinal ventral horn. However, a detailed analysis of anesthetic effects on ventral motor networks is lacking. We delivered isoflurane, desflurane, or propofol during NMDA/5-HT-induced, or noxious tail stimulus-evoked, fictive locomotion in neonatal rat isolated spinal cords. Anesthetics changed the frequency, amplitude, and regularity of fictive locomotion with little effect on phase-lag. Isoflurane abolished pharmacologically-induced versus noxious stimulus-induced motor output at similar concentrations. Propofol abolished pharmacologically-induced fictive locomotion through a γ-aminobutyric acid type A-receptor mechanism. Anesthetic effects on pharmacologically-elicted fictive locomotion appear clinically-relevant, and support a ventral horn immobilizing effect on locomotor rhythm generation.

Figure 1

Analysis of fictive locomotion. A) Example of L2 and L5 ventral root acitivity (bottom traces) during NMDA/5-HT-elicited fictive locomotion. Rectified and integrated activity (top two traces) was used to measure cycle period (T), amplitude, autocorrelation, phase-lag and coherence across 2–3 min of activity. B) Autocorrelation of L2 activity from A. Amplitude was used as a measure of rhythm regularity. C) Cross-correlation between L2 and L5 activity from A. Time lag (Lag) was used to calculate phase-lag as a proportion of cycle period T (phaselag= Lag/T). D) Frequency plot of spectral coherence between L2 and L5 activity. Peak coherence (coh) occurs around locomotor burst frequency (1/T). Coherence is the similarity between the cross-spectral and within-channel spectral content of two channels and measures coordination (phase-locking). Details can be found in our prior study [8] using coherence to study anesthetic effects.

Figure 2

General anesthetic effects on fictive locomotion. Examples from three individual animals showing effects of isoflurane (A) desflurane (B) and propofol (C). Thirty-seconds of ventral root activity is shown (bottom two traces) with rectified, integrated activity of corresponding ventral roots (top two traces). Isoflurane and desflurane abolished fictive locomotion at clinical concentrations, which recovered after washout. Propofol abolished fictive locomotion at low micromolar concentrations. which was reversed by picrotoxin, although cycle period remained greater than baseline.

Figure 3

Isoflurane effects on noxious tail stimulus-evoked ventral root activity using a hindquarter-attached preparation (diagram on left). Ventral root activity (bottom two traces) is rectified and integrated (top two traces). Noxious mechanical tail stimulation elicited rhythmic L2–L5 ventral root bursting, which was abolished by isoflurane concentrations similar to those that abolished NMDA/5-HT-elicted locomotion. The response recovered after isoflurane washout.