RESCUE OF COGNITIVE DEFICITS AND SYNAPTIC PLASTICITY USING TRANSCRANIAL ALTERNATING CURRENT STIMULATION IN A MOUSE MODEL OF TBI

Emerging non-invasive brain stimulation techniques, such as transcranial alternating current stimulation (tACS), in which current is passed through the skull in order to modulate neuronal activity through entrainment of oscillatory patterns without altering baseline excitability, represent a possible therapeutic intervention for cognitive deficits following traumatic brain injury (TBI). This study aimed to characterize the behavioral and molecular effects of using tACS at gamma and theta frequencies for treatment in the controlled cortical impact (CCI) model of TBI in mice. Male C57BL/6J mice (n = 27, 8 wks) were subjected to CCI surgery and allowed to recover for 1 month, after which animals were implanted with electrode receptacles for stimulation. All animals were then subject to a pre-treatment T-maze to get a baseline of working spatial memory ability. Mice were randomly assigned to receive either no treatment, gamma frequency tACS (40Hz), or theta frequency tACS (6 Hz). Animal tES stimulators were used to deliver stimulation (0.5 mA) for 20 minutes once per day for three days. A post-treatment T-maze was performed, after which animals were perfused for RT-qPCR analysis of regional gene expression. We found that gamma, but not theta, tACS, was able to significantly increase spontaneous alternation in T-maze, suggesting increased spatial working memory capacity. We found that gamma and theta tACS treated animals had significantly increased expression of synaptic plasticity related genes including BDNF, CAMK2B, and Synaptophysin. From our results we conclude that tACS can rescue cognitive and molecular deficits following TBI in a waveform-dependent manner.