Neurons change the way they respond to a specific stimulus by functional and structural changes, known as neuroplasticity. Neuroplasticity can be modified via different stimuli as electrical, chemical, and mechanical interventions, causing alterations to central and peripheral nervous system functions. Past neuroimaging studies related to chronic pain showed changes associated with altered cortical balance between excitation-inhibition and maladaptive plasticity. However, the mechanisms behind neuroplasticity and the optimal parameters which induce long-term, and sustainably enhanced performance remain unknown. Previous studies have shown that neuromodulation can induce beneficial changes through neuroplasticity. Therefore, in this study we focused on identifying the best strategies to induce neuroplasticity in the somatosensory cortex (S1). First, we tested if non-invasive repetitive transcranial magnetic stimulation (rTMS) induces neuronal excitability, and cell-specific magnetic activation via the Electromagnetic-Perceptive Gene (EPG). EPG is a novel gene that was identified and cloned from glass catfish (Kryptopterus vitreolus). In response to magnetic stimulation, this gene promotes neural activation, which could potentially restore cortical excitability. The results demonstrated that neuromodulation significantly improved long-term mobility, decreased anxiety, and enhanced neuroplasticity, reinforcing the growing amount of evidence from human and animal studies that are establishing neuromodulation as an effective strategy to promote plasticity and rehabilitation. Second, we identified the best protocol to facilitate the greatest changes in fMRI activation maps in the rat S1. The results showed that a single session of rTMS increased S1 activity, but induced changes that are absent three days after the session. Instead, forepaw stimulation of 10 Hz delivered synchronized with 10 Hz rTMS for five consecutive days demonstrated the greatest increase in the extent of the evoked fMRI responses. These results provide direct indication that pairing peripheral stimulation with rTMS induces long-term plasticity, and this phenomenon appears to follow a time-dependent plasticity mechanism. Given these results, we can conclude that neuromodulation induced by changes on S1 can improve cortical balance, and this therapy could be used in the future to treat different types of disorders.
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