Prefrontal corticostriatal disconnection blocks the acquisition of goal-directed action

Publication Type:
Journal Article
Journal of Neuroscience, 2018, 38 (5), pp. 1311 - 1322
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© 2018 the authors. The acquisition of goal-directed action requires encoding of the association between an action and its specific consequences or outcome. At a neural level, this encoding has been hypothesized to involve a prefrontal corticostriatal circuit involving the projection from the prelimbic cortex (PL) to the posterior dorsomedial striatum (pDMS); however, no direct evidence for this claim has been reported. In a series of experiments, we performed functional disconnection of this pathway using targeted lesions of the anterior corpus callosum to disrupt contralateral corticostriatal projections with asymmetrical lesions of the PL and/orpDMSto block plasticity in this circuit in rats. We first demonstrated that unilaterally blocking the PL input to the pDMS prevented the phosphorylation of extracellular signal-related kinase/mitogen activated protein kinase (pERK/pMAPK) induced by instrumental training. Next, we used a full bilateral disconnection of the PL from the pDMS and assessed goal-directed action using an outcome-devaluation test. Importantly, we found evidence that rats maintaining an ipsilateral and/or contralateral connection between thePLand thepDMSwere able to acquire goal-directed actions. In contrast, bilateral PL–pDMS disconnection abolished the acquisition of goal-directed actions. Finally, we used a temporary pharmacological disconnection to disrupt PL inputs to thepDMSby infusing theNMDAantagonist DL-2-amino-5-phosphonopentanoic acid into thepDMSduring instrumental training and found that this manipulation also disrupted goal-directed learning. These results establish that, in rats, the acquisition of new goal-directed actions depends on a prefrontal-corticostriatal circuit involving a connection between the PL and the pDMS.
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