Abnormal Striatal Activity in a Mouse Model of Impulse Control Disorder in Parkinson’s Disease

In this project, we studied cognitive behavior and striatal activity in a mouse model of impulse control disorder in Parkinson’s disease in which we administered the therapeutic dopamine D2/3R agonist, pramipexole. In food-deprived mice treated with bilateral striatal saline (healthy control) or 6-OHDA (mouse model of Parkinson’s Disease), we performed both open field locomotor assessments and operant testing to assess a cognitive phenomenon called delay discounting (DD). The operant box consisted of two (left and right) choice ports with beam breaks for nosepokes, and a central reward port that delivered milk. In some sessions, we administered pramipexole intraperitoneally prior to behavioral testing. In these mice, we performed simultaneous optically-identified single-unit electrophysiology using optrode arrays implanted in the dorsomedial striatum (DMS) of Drd1-Cre or A2a-Cre mice that expressed Cre-dependent ChR2-eYFP. Electrophysiology recordings were performed during either open field locomotor assessments or operant testing. During each cognitive assessment session, behavior was monitored by video tracking and/or operant box TTL events (nosepokes, cue lights, reward delivery, etc). During each electrophysiology session, DMS voltage signals were acquired using a Blackrock electrophysiology recording system. At the end of each session, blue light pulses (473 nm laser) were delivered to the optrode array (100 msec, 1 Hz, 4000 pulses) at a variety of light powers (0.5, 1, 2, 4 mW) by a lightweight patch cable. After recording sessions, we performed manual spike sorting (Plexon Offline Sorter) to isolate single units. We then aligned spiking activity to light pulses to identify optically-labeled neurons, and aligned all single-unit activity (labeled or not) to behavioral data.