RT Journal Article
SR Electronic
T1 Amphetamine disrupts haemodynamic correlates of prediction errors in nucleus accumbens and orbitofrontal cortex
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 802488
DO 10.1101/802488
A1 Emilie Werlen
A1 Soon-Lim Shin
A1 Francois Gastambide
A1 Jennifer Francois
A1 Mark D Tricklebank
A1 Hugh M Marston
A1 John R Huxter
A1 Gary Gilmour
A1 Mark E Walton
YR 2019
UL http://biorxiv.org/content/early/2019/10/13/802488.abstract
AB In an uncertain world, the ability to predict and update the relationships between environmental cues and outcomes is a fundamental element of adaptive behaviour. This type of learning is typically thought to depend on prediction error, the difference between expected and experienced events, and in the reward domain this has been closely linked to mesolimbic dopamine. There is also increasing behavioural and neuroimaging evidence that disruption to this process may be a cross-diagnostic feature of several neuropsychiatric and neurological disorders in which dopamine is dysregulated. However, the precise relationship between haemodynamic measures, dopamine and reward-guided learning remains unclear. To help address this issue, we used a translational technique, oxygen amperometry, to record haemodynamic signals in the nucleus accumbens (NAc) and orbitofrontal cortex (OFC) while freely-moving rats performed a probabilistic Pavlovian learning task. Using a model-based analysis approach to account for individual variations in learning, we found that the oxygen signal in the NAc correlated with a reward prediction error, whereas in the OFC it correlated with an unsigned prediction error or salience signal. Furthermore, an acute dose of amphetamine, creating a hyperdopaminergic state, disrupted rats’ ability to discriminate between cues associated with either a high or a low probability of reward and concomitantly corrupted prediction error signalling. These results demonstrate parallel but distinct prediction error signals in NAc and OFC during learning, both of which are affected by psychostimulant administration. Furthermore, they establish the viability of tracking and manipulating haemodynamic signatures of reward-guided learning observed in human fMRI studies using a proxy signal for BOLD in a freely behaving rodent.