Mediodorsal thalamus is critical for updating during extra-dimensional shifts but not reversals in the attentional set-shifting task

Abstract Cognitive flexibility, attributed to frontal cortex, is vital for navigating the complexities of everyday life. The mediodorsal thalamus (MD), interconnected to frontal cortex, may influence cognitive flexibility. Here male rats performed an attentional set-shifting task measuring intra-dimensional and extra-dimensional shifts in sensory discriminations. MD lesion rats needed more trials to learn the rewarded sensory dimension. However, once the choice response strategy was established, learning further two-choice discriminations in the same sensory dimension, and reversals of the reward contingencies in the same dimension, were unimpaired. Critically though, MD lesion rats were impaired during the extra-dimensional shift, when they must rapidly update the optimal choice response strategy. Behavioral analyses showed MD lesion rats had significantly reduced correct within trial second choice responses. This evidence shows transfer of information via the MD is critical when monitoring and rapid within trial updates in established choice response strategies are required after there is a rule change. Significance statement We demonstrate for the first time that rodent mediodorsal (MD) thalamus is a critical node when choice response strategies need to change rapidly after a within session rule change but not after reversals of reward contingencies during reward guided learning. MD interactions with orbitofrontal cortex are critical for value based learning, while MD interactions with medial prefrontal cortex are critical for rapid within trial updating of optimal choice response rules. MD interactions with the orbitofrontal cortex are not always necessary for reversal learning.