Subjects and Surgery

Subjects were 9–11 month-old wild type (WT) and BACHD transgenic line 5 (TG5) male and female rats. TG5 rats were generated and characterized by Yu-Taeger et al. (2012). Briefly, these transgenic Sprague-Dawley rats express the full-length mutant huntingtin gene with 97 CAG/CAA repeats under the control of the full-length human huntingtin promoter and regulatory elements (Yu-Taeger et al., 2012). TG5 rats at the age range used in the current study exhibit a progressive neuropathology and HD-like phenotype with motor abnormalities that closely resemble early onset HD (Yu-Taeger et al., 2012; Abada et al., 2013; Nagy et al., 2015). Animals were housed under standard conditions (temperature and humidity-controlled, 12-h light/dark cycle) with unrestricted access to food and water. All experiments were performed in accordance with protocols approved by the Rosalind Franklin University Institutional Animal Care and Use Committee. All TG5 rats were genotyped prior to experimentation. Animals were anesthetized with urethane (1.5 g/kg) and placed in a stereotaxic apparatus. Bipolar stimulating electrodes were implanted ipsilaterally into the motor cortex and the substantia nigra pars reticulata (SNr) as described previously (Threlfell et al., 2009; Sammut et al., 2010; Padovan-Neto et al., 2015). A recording electrode was also implanted into the contralateral motor cortex for the monitoring of local field potentials (Tseng et al., 2011). All recordings were performed while the animal was in a slow wave state (delta frequency). Glass extracellular recording electrodes were implanted into the dorsal striatum ipsilateral to cortical and SNr stimulating electrodes. Coordinates for electrode placement from Bregma were as follows: cortex – anterior: 3.7 mm, lateral: 2.0 mm; SNr – posterior: 5.0 mm, lateral: 2.5 mm; striatum – anterior: 0.7–1.2 mm, lateral: 2.0–4.0 mm; ventral from the surface of the brain: cortex: 2.0 mm; SNr: 8.0 mm; striatum: 3.0–7.0 mm (Paxinos and Watson, 2009). At the end of the experiment, rats were perfused with 4% paraformaldehyde and brains were processed for histological examination of electrode placements.