RT Journal Article SR Electronic T1 Pre-synaptic modulation of afferent feedback in the macaque spinal cord does not modulate with cycles of peripheral oscillations around 10 Hz JF bioRxiv FD Cold Spring Harbor Laboratory SP 012583 DO 10.1101/012583 A1 Ferran Galán A1 Stuart N. Baker YR 2014 UL http://biorxiv.org/content/early/2014/12/12/012583.abstract AB Spinal interneurons are partially phase-locked to physiological tremor around 10Hz. The phase of spinal activity is approximately opposite to descending drive to motoneurons, leading to partial phase cancellation and tremor reduction. Pre-synaptic inhibition of afferent feedback has been demonstrated to increase during voluntary movements, but it is not known whether it tracks more rapid fluctuations in output such as during tremor.In this study, we recorded dorsal root potentials (DRPs) from the C8 and T1 roots in two macaque monkeys following intra-spinal micro-stimulation (1–3Hz, 30–100μA), whilst the animals performed an index finger flexion task which elicited substantial peripheral oscillations around 10Hz. Forty one responses were identified with latency < 5 ms; these were narrow (mean width 0.59 ms), and likely resulted from antidromic activation of afferents following stimulation near terminals. Significant modulation during task performance occurred in 16/41 responses, reflecting terminal excitability changes generated by pre-synaptic inhibition (Wall’s excitability test).Stimuli falling during large-amplitude 8–12Hz oscillations in finger acceleration were extracted, and sub-averages of DRPs constructed for stimuli delivered at different oscillation phases. Although some apparent phase-dependent modulation was seen, this was not above the level expected by chance fluctuation.We conclude that although pre-synaptic inhibition modulates over the timescale of a voluntary movement (around one second), it does not follow more rapid changes in motor output. This suggests that pre-synaptic inhibition is not part of the spinal systems for tremor reduction described previously, and that it plays a role in overall – but not moment-by-moment – regulation of feedback gain.KEY POINTSPresynaptic inhibition of afferent feedback is known to modulate during voluntary movementsSpinal interneuron circuits have previously been demonstrated to modulate activity with the phase of ∼10 Hz physiological tremor, in a manner which promotes cancellation of oscillations and hence tremor reductionIn this study, we investigated whether afferent pre-synaptic inhibition could also modulate on the faster timescale of tremor oscillationsAlthough we found evidence for task-dependent modulation of pre-synaptic inhibition (a timescale of around 1 s), there was no evidence for modulation with the phase of tremor (timescale around 100 ms)The results suggest that pre-synaptic inhibition modulates afferent feedback gain dependent on overall motor state, rather than in response to moment-by-moment fluctuations in output