1288 The Rostral Zona Incerta: A Promising DBS Target for Modulating Disordered Reward Behavior

INTRODUCTION: The Zona Incerta has traditionally been a deep brain stimulation (DBS) target for treating movement disorders. However, recent evidence suggests that it may be involved in processing of higher-order behaviors including reward, novelty, and appetite. In particular, its rostral subcomponent, the Rostral Zona Incerta (ZIr), is well placed to serve as an integrative hub for reward processing, given its widespread interconnectivity with numerous cortical and subcortical structures including the ventral tegmental area and lateral habenula. Accordingly, the ZIr may be an appealing target for modulating reward behavior in diseases such as obsessive-compulsive disorder (OCD), substance use disorders, and obesity. METHODS: We trained head-fixed, water-restricted C57BL6 mice (n = 2) to perform a classical conditioning task where they learned to associate audio-visual cues with either 100%, 90%, or 0% water reward probability. 32-channel silicon electrodes were implanted into the ZIr to record single unit activity. Data were band-pass filtered and digitized at 30 kHz. Spike sorting and data analyses were performed in Matlab. The Wilcoxon Rank Sum test was used to compare neuronal spike counts; a pre-specified alpha of < 0.05 was used to define statistical significance. RESULTS: We recorded from a total of 249 ZIr neurons across 200 trials. Of recorded neurons, 81 (32.5%) demonstrated a significant modulation of firing in response to reward-predicting cues relative to cues predicting no reward. Additionally, 29 (11.7%) demonstrated a significant modulation of firing rate in response to reward delivery itself, relative to absent rewards. CONCLUSIONS: These data suggest that the ZIr is involved in reward processing. Accordingly, the ZIr may be a promising DBS target for modulating diseases with disordered reward, including OCD, drug use disorders, and obesity.