EP 68. Identification of electrophysiological biomarkers in a novel animal model of Tourette Syndrome

Abstract

Introduction Treating Tourette syndrome (TS) remains challenging as therapies fail to take temporal presentation of symptoms into account. Therefore, to optimize therapies the investigation of biomarkers predicting repetitive behavior is required. Objectives We are currently studying repetitive behavior and associated electrophysiological changes in a new animal model of Tourette syndrome – the dopamine transporter (DAT) over-expressing rat model. The DAT rat resembles TS pathology in various aspects, including marked up-regulation of D2/D1 receptors, brain site-specific dopamine alterations and decrease in parvalbumin expressing interneurons in the caudate putamen. In line with clinical findings, the DAT rats display time-locked increase in tic-like behavior following amphetamine application. Math/meth To study stereotypic behavior, extracellular bipolar in vivo recordings were conducted under urethane anesthesia in different areas of the basal-ganglia thalamo-cortical loop for 4 h (2 h before (baseline) and 2 h after amphetamine). Signals were amplified, filtered (0.05–250 Hz) and sampled at 1 kHz. Power Spectral Densities were calculated using Spike 2 software (FFT size 1024/0.0256 s, Hanning Window) for baseline and post amphetamine time-windows, where behavioral analysis revealed stereotypy or not. Power-spectra were normalized to the mean s. d. of power between 103–147 Hz and 153–197 Hz power. Results Results show that DAT rats at the time-point of tic induction, exhibit time-locked abnormalities in alpha and beta bands, especially in the dorsomedial thalamus. This indicates characteristic electrophysiological modulation temporally related to distinct repetitive behavior. Conclusion The time-locked manifestation allows us to further investigate biomarkers of repetitive behavior and to employ this in constructing a close-loop stimulation device treating repetitive behavior in a controlled fashion.