Dynamic mesolimbic dopamine signaling during action sequence learning and expectation violation

Abstract

Prolonged mesolimbic dopamine concentration changes have been detected during spatial navigation, but little is known about the conditions that engender this signaling profile or how it develops with learning. To address this, we monitored dopamine concentration changes in the nucleus accumbens core of rats throughout acquisition and performance of an instrumental action sequence task. Prolonged dopamine concentration changes were detected that ramped up as rats executed each action sequence and declined after earned reward collection. With learning, dopamine concentration began to rise increasingly earlier in the execution of the sequence and ultimately backpropagated away from stereotyped sequence actions, becoming only transiently elevated by the most distal and unexpected reward predictor. Action sequence-related dopamine signaling was reactivated in well-trained rats if they became disengaged in the task and in response to an unexpected change in the value, but not identity of the earned reward. Throughout training and test, dopamine signaling correlated with sequence performance. These results suggest that action sequences can engender a prolonged mode of dopamine signaling in the nucleus accumbens core and that such signaling relates to elements of the motivation underlying sequence execution and is dynamic with learning, overtraining and violations in reward expectation.

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation

“…Principal component regression, a chemometric technique that combines principal component analysis with inverse least-squares regression (Heien et al, 2005), was used to isolate changes in current due to dopamine and pH from the cyclic voltammetric data. We used a standard training set of dopamine, pH, and drift CVs as has been described previously (Aitken et al, 2016;Collins et al, 2016). This procedure allowed us to distinguish changes in current due to dopamine fluctuations from changes due to pH or to other electroactive substances.…”

“…For Experiment 1, training and testing took place in a set of 16 Med Associates (East Fairfield, VT) operant chambers described previously (Malvaez et al, 2015). For Experiment 2, training and testing were conducted in a set of two chambers identical to the training chambers, but outfitted with a voltammetric recording unit as described previously (Aitken et al, 2016;Collins et al, 2016).…”

“…For each test session, rats were placed in the operant chamber and tethered to the voltammetric recording unit through an electrical swivel. Fast-scan cyclic voltammetry (FSCV) recordings were performed during the PIT tests as described previously (Aitken et al, 2016;Collins et al, 2016). On each test day, after stabilization of the baseline current (~20 min), rats were unilaterally infused as described above and the baseline was allowed to restabilize for 5-10 min, after which the PIT test commenced with the onset of the house light and insertion of the lever.…”

“…Following surgery, rats were individually housed and allowed to recover for 5-7 days. Placement(s) were verified using the standard histological procedures described previously (Collins et al, 2016); (see Supplementary Figures 1 and 2). …”

“…Carbon-fiber microelectrodes were prepared and calibrated (average calibration factor = 45.45 nM/nA, SEM = 4.13) as described previously (Clark et al, 2010;Collins et al, 2016;Wassum et al, 2013), with the exception that the silica shaft encasing the carbon fiber was cut to~12 mm. Following calibration, each electrode was affixed to a 22-gauge, stainless steel guide cannula (Plastics One) with the cannula extending 3-4 mm beyond the 14-mm plastic threaded base.…”