Differential effects of inactivation of the orbitofrontal cortex on strategy set-shifting and reversal learning

Different subregions of the rodent prefrontal cortex (PFC) mediate dissociable types of behavioral flexibility. For example, lesions of the medial or orbitofrontal (OFC) regions of the PFC impair extradimensional shifts and reversal learning, respectively, when novel stimuli are used during different phases of the task. In the present study, we assessed the effects of inactivation of the OFC on strategy set-shifting and reversal learning, using a maze based set-shifting task mediated by the medial PFC. Long-Evans rats were trained initially on a visual-cue discrimination to obtain food. On the subsequent day, rats had to shift to using a response strategy (e.g., always turn left). On Day 3 (reversal), rats were required to reverse the direction of their turn (e.g., always turn right). Infusions of the local anesthetic bupivacaine into the OFC did not impair initial visual discrimination learning, nor did it impair performance on the set-shift. In contrast, inactivation of the OFC did impair reversal learning; yet, these rats ceased using the previously acquired response rule as readily as controls. Instead, rats receiving OFC inactivations made a disproportionate number of erroneous arm entries towards the visual-cue, suggested that these animals reverted back to using the original visual-cue based strategy. These findings, in addition to previous data, further support the notion that the OFC and medial PFC play dissociable roles in reversal learning and set-shifting. Furthermore, the lack of effect of OFC inactivations on the set-shift indicates that this type of behavioral flexibility does not require cognitive operations related to reversal learning.

[1]  S. Floresco,et al.  Cerebral Cortex doi:10.1093/cercor/bhl073 Thalamic--Prefrontal Cortical--Ventral Striatal Circuitry Mediates Dissociable Components of Strategy Set Shifting , 2006 .

[2]  V. Brown,et al.  Orbital prefrontal cortex mediates reversal learning and not attentional set shifting in the rat , 2003, Behavioural Brain Research.

[3]  M. Ragozzino,et al.  The contribution of the rat prelimbic-infralimbic areas to different forms of task switching. , 2003, Behavioral neuroscience.

[4]  Geoffrey Schoenbaum,et al.  Orbitofrontal lesions in rats impair reversal but not acquisition of go, no-go odor discriminations , 2002, Neuroreport.

[5]  T. Robbins,et al.  Effects of orbitofrontal, infralimbic and prelimbic cortical lesions on serial spatial reversal learning in the rat , 2007, Behavioural Brain Research.

[6]  T. Bussey,et al.  Effects of selective thalamic and prelimbic cortex lesions on two types of visual discrimination and reversal learning , 2001, The European journal of neuroscience.

[7]  M. Ragozzino,et al.  The effects of dopamine D(1) receptor blockade in the prelimbic-infralimbic areas on behavioral flexibility. , 2002, Learning & memory.

[8]  S. Floresco,et al.  Dissociable Roles for the Nucleus Accumbens Core and Shell in Regulating Set Shifting , 2006, The Journal of Neuroscience.

[9]  T. Robbins,et al.  Dissociable Contributions of the Orbitofrontal and Infralimbic Cortex to Pavlovian Autoshaping and Discrimination Reversal Learning: Further Evidence for the Functional Heterogeneity of the Rodent Frontal Cortex , 2003, The Journal of Neuroscience.

[10]  J. Price,et al.  Effects of excitotoxic lesions in the ventral striatopallidal–thalamocortical pathway on odor reversal learning: inability to extinguish an incorrect response , 2000, Experimental Brain Research.

[11]  C. Gerfen,et al.  The frontal cortex-basal ganglia system in primates. , 1996, Critical reviews in neurobiology.

[12]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[13]  B. Kolb,et al.  Double dissociation of spatial impairments and perseveration following selective prefrontal lesions in rats. , 1974, Journal of comparative and physiological psychology.

[14]  V. Brown,et al.  Difficulty Overcoming Learned Non‐reward during Reversal Learning in Rats with Ibotenic Acid Lesions of Orbital Prefrontal Cortex , 2007, Annals of the New York Academy of Sciences.

[15]  V. Brown,et al.  Medial Frontal Cortex Mediates Perceptual Attentional Set Shifting in the Rat , 2000, The Journal of Neuroscience.

[16]  R. Kesner,et al.  Involvement of the Prelimbic–Infralimbic Areas of the Rodent Prefrontal Cortex in Behavioral Flexibility for Place and Response Learning , 1999, The Journal of Neuroscience.

[17]  S. Floresco,et al.  Multiple Dopamine Receptor Subtypes in the Medial Prefrontal Cortex of the Rat Regulate Set-Shifting , 2006, Neuropsychopharmacology.

[18]  Bita Moghaddam,et al.  Glutamate receptors in the rat medial prefrontal cortex regulate set-shifting ability. , 2003, Behavioral neuroscience.

[19]  Michael E. Ragozzino,et al.  The involvement of the orbitofrontal cortex in learning under changing task contingencies , 2005, Neurobiology of Learning and Memory.