(A-36) Dopamine Release in the Monkey Striatum and Anticipatory Licking

Introduction:: The neurotransmitter dopamine (DA) has long been implicated to play a role in movement, motivation regulation, and reward learning. Great evidence shows that DA release during a given trial, the portion of a behavioral task which contains reward predictive cues and reward presentation after the completion of a desired behavioral response to the reward predictive cues, act as a teaching signal known as a reward prediction error. In contrast, the function of DA release during the intertrial interval (ITI), the time from when a trial ends until the next trial starts which does not contain any reward or reward predictive information, has not been explored in such depth. In a study released in Schwerdt et al. Sci. Adv. 2020, DA release, local field potentials, and non-neurological physiological responses were simultaneously recorded from monkeys during a visually guided reward-biased saccade task. Anticipatory licking, which has been known to serve as a metric for learning and motivation, was one of these physiological responses recorded. This research hopes to determine if ITI DA release could play a role in regulating the anticipatory licking response of a monkey during future trials, which could provide further insight into DA’s functions of motivation and reward learning.

Materials and Methods:: Monkeys were trained on a visually guided reward-biased saccade task. The monkeys would first fixate on a central cue for 1.6 seconds, then saccade to a peripheral target and maintain fixation for 4 seconds, after which they would receive a liquid food reward. Whether the peripheral target appeared on the left or right of the central cue would inform the monkey if completion of the current trial would result in a big (0.3 mL) or small (0.1 mL) liquid food reward. Licking data was measured as the summed 3-axis magnitude of an accelerometer (SparkFun, MMA8452Q) attached to the food delivery tube, and DA concentration was computed through fast scan cyclic-voltammetry recordings. The ITI over which DA concentrations were analyzed was defined to begin 2 seconds after the current trial outcome (reward or error, when the monkey breaks fixation from either the central or peripheral targets) until the start of the next trial 8 seconds later. DA concentrations were background subtracted relative to the start of the following trial. Within-trial licking responses were computed as the area under the curve of the measured licking responses during the 0- to 2- second window after the peripheral cue was displayed. These responses were then quantiled to separate trials with higher and lower within-trial licking (Figure 1). ITI licking data was sectioned based on visual inspection to account for a monkey’s differing response to food delivery (e.g. licking versus sucking the tube, Figure 2). All data analysis was conducted in MATLAB (R 2022b).

Results, Conclusions, and Discussions:: Within-trial licking analyses were performed to determine if ITI DA signaling could influence the vigor of a monkey’s licking response in future trials. Early results show that ITI DA release exhibited different patterns prior to trials with higher versus lower within-trial licking with a higher frequency of differing release dynamics occurring in the caudate nucleus than the putamen (Figure 1). This observation supports canonical DA theories of reinforcement and motivation, as seen by the within-trial licking responses. ITI licking analyses were then performed in hopes of determining relevant timepoints during the ITI in which to further investigate the online regulation of anticipatory licking from DA. Licking traces during the ITI were compared following successful big and small reward trials as these trial conditions produce the greatest variability in licking responses. Preliminary results show the greatest difference in ITI licking during the first 2 seconds of the ITI, 2-4 seconds after the presentation of reward (Figure 2). Several sessions showed licking differences up to 6 seconds after reward presentation, and a smaller number of sessions showed differences for the entire ITI. These observations call for the further analysis of DA release throughout the monkey’s striatum during these periods and how these dynamics differ across sessions with longer periods of ITI licking variance. Future work with this data aims to better classify the online relationship between licking and DA during the ITI. This will include covariance and regression analyses that hope to decouple DA’s encoding of reward alone and licking’s ability to predict DA responses over time, respectively. Additionally, it will also be important to investigate DA’s correlation to licking during both successful and error trials. It has been seen that within-trial DA release is amplified on successful trials following error trials, but this affect has not been explored and correlated to behavioral responses during the ITI.

Acknowledgements (Optional): : Funding information: 

Funding was provided by the Bioengineering department of the Swanson School of Engineering and the Office of the Provost at the University of Pittsburgh. 

NIH/NINDS R00 - 5R00NS107639-04

Michael J. Fox Foundation (MJFF) Aligning Science Across Parkinson’s (ASAP) - ASAP-020-519

References (Optional): : H. N. Schwerdt, et al., Dopamine and beta-band oscillations differentially link to striatal value and motor control. Sci. Adv. 6, eabb9266 (2020). DOI: 10.1126/sciadv.abb9226