Pharmacologically induced enhancement of recurrent inhibition in humans: effects on motoneurone discharge patterns - PubMed (original) (raw)
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Pharmacologically induced enhancement of recurrent inhibition in humans: effects on motoneurone discharge patterns
Benjamin Mattei et al. J Physiol. 2003.
Abstract
The aim of the present study was to investigate the effects of spinal recurrent inhibition on human motoneurone discharge patterns. The tonic discharge activity of motor unit pairs was recorded in the extensor carpi radialis (ECR) and abductor digiti minimi (ADM) muscles during voluntary isometric contraction. While undergoing continuous intravenous saline (NaCl 0.9 %) perfusion, the subjects were given a short lasting injection of L-acetylcarnitine (L-Ac), which has been found to potentiate recurrent inhibition in humans. The variability, synchronization and coherence of the motor unit discharges were analysed during four successive test periods (lasting 2-3 min each). A significant decrease in the inter-spike interval (ISI) coefficient of variation was observed in the discharge patterns of the motor units tested in the ECR and not in the ADM, which were not accompanied by any consistent changes in the mean ISIs of the motor unit activity in either muscle. The L-Ac injection also led to a significant increase in the synchronization in half of the motor unit pairs tested in the ECR muscle (n = 29), whereas no consistent changes were observed with the ADM motor units (n = 25). However, coherence analysis failed to reveal any consistent differences in the incidence of significant values of coherence spectrum between the pre-injection and injection periods among the motor unit pairs tested with either saline or L-Ac injections, in either the ECR or ADM muscles. The contrasting effects on the variability and the synchronization of the motor unit discharges observed with ECR motoneurones known to undergo recurrent inhibition and with ADM motoneurones known to lack recurrent inhibition suggest that the drug may have specific effects which are mediated by an enhancement of the Renshaw cell activity. The decrease in the ISI variability is in line with the hypothesis that recurrent inhibition may contribute along with the post-spike after-hyperpolarization to limiting the influence of the synaptic noise on the firing times of steadily discharging motoneurones. The present data, which suggest that recurrent inhibition plays a synchronizing rather than a desynchronizing role, are in keeping with the fact that the Renshaw cells may provide an important source of common inhibitory inputs.
Figures
Figure 1. Experimental procedure and analysis of the effects of l-Ac intravenous injection on the discharge patterns of a motor unit pair recorded in the ECR muscle
While undergoing a continuous saline (NaCl 0.9 %) perfusion, the subject had to use the auditory biofeedback information provided to keep two ECR motor units (MUs) recorded by means of two intramuscular microelectrodes discharging steadily. After about 3 min, a short lasting injection of
l
-Ac was administered instead of the saline perfusion. The ISI CV (CV = ISI
s.d.
/mean ISI) of the firing rate of each motor unit (A) and the synchronization (B) were analysed during four successive test periods, before (Pre
l
-Ac), during (
l
-Ac) and after (Post
l
-Ac1 and Post
l
-Ac2) the
l
-Ac injection. The presence of synchronization peaks was determined by computing the cross-correlation histograms (± 100 ms) and cumulative sums (CUSUM; Ellaway, 1978). Only the central parts of the cross-correlation histograms (± 50 ms) are shown in B, in order to focus on the peak region. The peak significance was assessed by determining the z score (z > 3.27; Garnett & Stephens, 1980) and the synchronization strength was assessed in terms of the synchronous impulse probability (SIP). The motor unit macro-potential (macro-MUP) was periodically extracted by spike-triggered averaging the surface EMG activity to ensure that the same motor units were being tested throughout the experimental session. N, number of triggering impulses.
Figure 6. Example of the changes induced by l-Ac injection on the synchronization and coherence between the discharge patterns of two ECR motor units
Cross-correlation histogram analysis on one ECR recording session showing changes in synchronization during the saline pre-injection (A) and
l
-Ac injection periods (C), and analysis of the coherence spectra in the frequency band 0–70 Hz (B and D, respectively) during the same test periods. The net differences between the coherence values measured during both periods are plotted in E after subtracting B from D. A significant (P < 0.05) decrease was observed at 2 Hz, whereas significant increases occurred at 16 and 47 Hz (asterisks).
Figure 2. Effects of the l-Ac injection on the discharge variability of the motor units recorded in the ECR (A) and in the ADM (B) muscles
The mean value of the ISI CV of the ECR motor units was significantly smaller (P = 0.02) during
l
-Ac injection (A, filled circles) than during the Pre
l
-Ac period. No such effect was observed on the firing pattern of the ADM motor units (B, filled triangles). In the control experiments in which
l
-Ac injection was replaced by saline injection (Saline 2; single-blind procedure), the variability of the firing rates of the motor units recorded in the ECR (A, open circles) and ADM (B, open triangles) muscles increased gradually in the course of the recording sessions.
Figure 3. Effects of the l-Ac injection on the synchronization of motor unit pairs tested in the ECR muscle
With the χ2 test procedure described in the Methods, nine ECR motor unit pairs showed a significant increase in their synchronization during
l
-Ac injection (A, continuous lines). No significant changes were observed in the control sessions (B) in which
l
-Ac injection was replaced by a saline injection (Saline 2). In A and B, the open triangles and arrows indicate the motor unit pairs that were not significantly synchronized in the pre-injection (
l
-Ac or Saline) period. Upon pooling the data (C, filled circles), the mean strength of the motor unit pair synchronization was found to be significantly greater during
l
-Ac injection (P < 0.001) and during the Post
l
-Ac1 test period (P = 0.015) than during the Pre
l
-Ac period. Pooled data from control sessions with saline perfusion alone showed the occurrence of no significant changes in the synchronous motor unit pattern (C, open circles).
Figure 4. Effects of the l-Ac injection on the synchronization of motor unit pairs tested in the ADM muscle
No significant changes in the synchronization of ADM motor units were observed during
l
-Ac injection (A) or during the control saline injection (B, Saline 2). In A and B, the open triangles and arrows indicate the motor unit pairs that were not significantly synchronized in the pre-injection (
l
-Ac or Saline) period. This finding was confirmed upon pooling the data (C) obtained in the drug sessions (filled triangles) and control sessions (open triangles).
Figure 5. Relationships between the changes in synchronization and discharge variability of each motor unit pair tested in the ECR (A) and ADM (B) muscles during l-Ac and saline pre-injection periods
The changes in the synchronization peak area and in the mean geometric CV were assessed by subtracting the values of each parameter assessed during the saline pre-injection period from those assessed during the
l
-Ac (filled symbols) or saline (open symbols) injection period. A total number of eight (A, filled stars) out of the nine ECR motor unit pairs which discharged with a significantly greater synchrony during
l
-Ac injection also discharged with a lower variability. No such effects were observed in the ADM muscle (B).
Figure 7. Population analysis of the incidence of significant coherence in ECR and ADM muscles during l-Ac or saline injection
The percentage of the motor units tested in the ECR (A and B) and ADM (C and D) muscles showing significant coherence values are plotted in the 0–100 Hz frequency range (abscissa) during the pre-injection (dashed lines) and injection period (continuous lines) with either saline (A and C) or
l
-Ac (B and D) injections. All the motor unit pairs tested in the ECR and ADM muscles showed significant coherence values within 0–10 Hz. In the 10–40 Hz frequency band the incidence of significant values tended to be higher in the ADM muscle than in the ECR muscle. In the motor unit population analysis, the χ2 test did not show the occurrence of any significant changes during either saline or
l
-Ac injection as compared to the pre-injection period in either of the muscles tested.
References
- Adam D, Windhorst U, Inbar GF. The effects of recurrent inhibition on the cross-correlated firing patterns of motoneurones (and their relation to signal transmission in the spinal cord-muscle channel) Biol Cyber. 1978;29:229–235. -PubMed
- Baker SN, Kilner JM, Pinches EM, Lemon RM. The role of synchrony and oscillations in the motor output. Exp Brain Res. 1999;128:109–117. -PubMed
- Calvin WH, Stevens CF. Synaptic noise and other sources of randomness in motoneuron interspike intervals. J Neurophysiol. 1968;31:574–587. -PubMed
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