Characterizing Excitatory-Inhibitory Balance in Conscious Rodents via Paired pulse TMS

BACKGROUND: Transcranial magnetic stimulation is an established neuromodulation technique; however, its molecular and cellular mechanisms is still unknown. Most of the TMS studies in rodents have been conducted in anesthetized conditions, typically using single-pulse paradigms. NEW METHOD: We systematically evaluated both single-pulse and paired-pulse TMS parameters in unanaesthetised rats. All TMS protocols were recorded in awake and restrained rats. Motor thresholds & Motor-Evoked Potentials were determined by single-pulse stimulation. Paired-pulse protocols, including short-interval intracortical inhibition (SICI, 1-5 ms), intracortical facilitation (ICF, 20 ms), short-interval intracortical facilitation (SICF, 3 ms), and long-interval intracortical inhibition (LICI, 100 ms) were used to assess intracortical circuitry. RESULTS: The motor threshold (21.58 ± 2.9%) and latency (3.66 ± 0.46 ms) of MEPs obtained with a single pulse paradigm demonstrated consistent responses. The response to paired stimulation for SICI (ISI-2ms) was 218% higher than the unconditioned response while ICF, SICF, and LICI showed a 42% increase, 235% increase, and ~90% decrease respectively. COMPARISON WITH EXISTING METHODS: In contrast to previous rodent TMS investigations conducted under anesthesia, this work recorded single-pulse and paired-pulse TMS measures in unanesthetized rats. This is the first report of paired-pulse TMS measurements in awake rats. Single-pulse TMS produced localized, stimulus-locked forelimb MEPs, similar to human research; in paired-pulse paradigms, ICF, LICI, and SICF showed human-like patterns, whereas SICI showed facilitation rather than inhibition. CONCLUSIONS: TMS single and paired pulse paradigms can be recorded and replicated in rodents in unanaesthetized state establishing a translational platform to investigate the mechanism of TMS.