Abstract
ABSTRACTMuch evidence suggests that reversal learning is mediated by cortico-striatal circuitries with the orbitofrontal cortex (OFC) playing a prominent role. The OFC is a functionally heterogeneous region, but potential differential roles of lateral (lOFC) and medial (mOFC) portions in visual reversal learning have yet to be determined. We investigated the effects of pharmacological inactivation of mOFC and lOFC on a deterministic serial visual reversal learning task for rats. For reference, we also targeted other areas previously implicated in reversal learning: prelimbic (PrL) and infralimbic (IL) prefrontal cortex, and basolateral amygdala (BLA). Inactivating mOFC and lOFC produced opposite effects; lOFC impairing, and mOFC improving, performance in the early, perseverative phase specifically. Additionally, mOFC inactivation enhanced negative feedback sensitivity, while lOFC inactivation diminished feedback sensitivity in general. mOFC and lOFC inactivation also affected novel visual discrimination learning differently; lOFC inactivation paradoxically improved learning, and mOFC inactivation had no effect. We also observed dissociable roles of the OFC and the IL/PrL. Whereas the OFC inactivation affected only perseveration, IL/PrL inactivation improved learning overall. BLA inactivation did not affect perseveration, but improved the late phase of reversal learning. These results support opponent roles of the rodent mOFC and lOFC in deterministic visual reversal learning.
Highlights
The fundamental ability to flexibly change behavior in response to situational changes is disrupted in several psychiatric and developmental disorders including obsessive compulsive disorder (OCD), schizophrenia, and autism (Waltz and Gold 2007; Chamberlain et al 2008; Leeson et al 2009; D’Cruz et al.2013)
We investigated the effects of pharmacological inactivation of medial OFC (mOFC) and lateral OFC (lOFC) on a deterministic serial visual reversal learning task for rats
Of the 71 animals entering the reversal learning experiment, 57 rats were included in the analysis based on histological assessment of regional infusion sites; comprising of 14, 12, 8 (IL), 11 (PrL), and 13 (BLA) rats with correct regional injector placements (Fig. 2)
Summary
The fundamental ability to flexibly change behavior in response to situational changes is disrupted in several psychiatric and developmental disorders including obsessive compulsive disorder (OCD), schizophrenia, and autism (Waltz and Gold 2007; Chamberlain et al 2008; Leeson et al 2009; D’Cruz et al.2013). Dissociable Roles of Rat Medial and Lateral Orbitofrontal Cortex Hervig et al 1017 This requires different cognitive processes including the ability to suppress the tendency to persist with the previously rewarded response, learning the new contingencies, and choosing the previously unrewarded (but rewarded) option. The OFC is critical for reversal learning in marmoset monkeys (Dias et al 1996; Clarke et al 2008) and a vast amount of evidence implicates the lateral OFC (lOFC) in rodents (Schoenbaum et al 1999, 2000, 2003; Bohn et al 2003; McAlonan & Brown 2003; Kim & Ragozzino 2005; Burke et al 2009; Takahashi et al 2009; see review by Izquierdo et al 2017). LOFC inactivation (Alsiö et al 2015) and excitotoxic lesioning (Graybeal et al 2011) impair deterministic visual serial reversal learning in rodents, the effects of mOFC inactivation have not previously been determined in this setting
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
