Possible differences between the time courses of presynaptic and postsynaptic GABAB mediated inhibition in the human motor cortex

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Abstract
Paired-pulse transcranial magnetic stimulation (TMS) can be used to non-invasively evaluate human motor cortical inhibitory circuits such as short interval intracortical inhibition (SICI) and long interval intracortical inhibition (LICI). Pharmacological studies suggested that SICI is mediated by GABAA receptors while LICI is probably mediated by GABAB receptors. A previous study also showed that SICI and LICI are mediated by separate neuronal populations and that LICI inhibits SICI, possibly through presynaptic GABAB receptors. The aim of this study was to examine whether the time course of motor-evoked potentials (MEP) inhibition by LICI, likely mediated through postsynaptic GABAB receptors, is different from SICI inhibition by LICI, likely mediated through presynaptic GABAB receptors. Nine healthy volunteers were studied and MEP were recorded from the first dorsal interosseous muscle. A triple-stimulus TMS paradigm was used to evaluate the effect of LICI at ISIs of 100 and 150 ms on SICI. LICI at 100 and 150 ms caused a similar degree of MEP inhibition. LICI at 100 ms led to a significant reduction of SICI but LICI at 150 ms had no effect on SICI. Repeated measures ANOVA revealed a significant interaction between the LICI mediated inhibition of SICI and ISI (P = 0.0072). These findings suggest that the time courses of presynaptic and postsynaptic GABAB receptors mediated inhibition are different in the human motor cortex.

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