Afferent Presynaptic Inhibition Research Articles

Pre-Synaptic Inhibition of Afferent Feedback in the Macaque Spinal Cord Does Not Modulate with Cycles of Peripheral Oscillations Around 10 Hz.

Spinal interneurons are partially phase-locked to physiological tremor around 10 Hz. The phase of spinal interneuron activity is approximately opposite to descending drive to motoneurons, leading to partial phase cancellation and tremor reduction. Pre-synaptic inhibition of afferent feedback modulates during voluntary movements, but it is not known whether it tracks more rapid fluctuations in motor output such as during tremor. In this study, dorsal root potentials (DRPs) were recorded from the C8 and T1 roots in two macaque monkeys following intra-spinal micro-stimulation (random inter-stimulus interval 1.5–2.5 s, 30–100 μA), whilst the animals performed an index finger flexion task which elicited peripheral oscillations around 10 Hz. 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 8–12 Hz 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. We conclude that, although terminal excitability reflecting pre-synaptic inhibition of afferents modulates over the timescale of a voluntary movement, 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.

Effects of two benzodiazepines, phenobarbitone, and baclofen on synaptic transmission in the cat cuneate nucleus.

The effects of diazepam, flunitrazepam, phenobarbitone and baclofen on excitatory as well as on pre- and postsynaptic inhibitory processes in the cuneate nucleus were studied in decerebrate cats. Afferent presynaptic inhibition in the cuneate nucleus, evoked by volleys in the median nerve, and assessed by the size of the positive cuneate surface potential (P wave), the dorsal column reflex (DCR), and the increased excitability of primary afferent terminals of the ulnar nerve, was markedly enhanced by diazepam (0.1-3.0 mg/kh i.v.) and flunitrazepam (0.01-0.3 mg/kg i.v.), slightly enhanced by lower doses of phenobarbitone (3-20 mg/kg i.v.), but depressed by baclofen (1-10 mg/kg i.v.). Diazepam, flunitrazepam and phenobarbitone also increased postsynaptic inhibition in the cuneate nucleus which was measured by the decrease after conditioning volleys in the median nerve of the short-latency lemniscal response to cuneate stimulation. The GABA receptor blocking agent, picrotoxin, antagonized the effects of diazepam on pre- and postsynaptic inhibition in a surmountable way. After thiosemicarbazide (TSC), an inhibitor of GABA synthesis, both pre- and postsynaptic inhibition were greatly reduced and the augmenting effect of diazepam on both types of inhibition was nearly abolished. Aminooxyacetic acid (AOAA), an inhibitor of GABA degradation, slightly enhanced pre- and postsynaptic inhibition; the effects of diazepam were unaffected by AOAA. Diazepam, flunitrazepam and phenobarbitone did not alter the resting excitability of primary afferent endings or of cuneo-thalamic relay (CTR) cells in the cuneate nucleus. After higher doses (30 mg/kg i.v.) of phenobarbitone pre- and postsynaptic inhibition, which were enhanced by 10 mg/kg of this drug, tended to return to pre-drug values or below. Phenobarbitone, in contrast to benzodiazepines, also depressed in a dose-dependent way the N wave, which is an index of the orthodromic excitation of the CTR cells. Baclofen strongly depressed the cuneate N wave, decreased the excitability of CTR cells, reduced pre- and postsynaptic inhibition, but had no effect on the resting excitability of primary afferent endings. Our findings suggest the following modes of action of the above mentioned drugs: 1. benzodiazepines enhance selectively the GABA-mediated pre- and postsynaptic inhibition in the cuneate nucleus; 2. phenobarbitone slightly enhances pre- and postsynaptic inhibition only in a narrow dose range, and in addition reduces the excitatory processes in the cuneate nucleus; 3. baclofen seems to depress the excitation of cuneate relay cells and interneurones postsynaptically; the depression of relay cells is probably nonspecific.