Encoding Changes in Orbitofrontal Cortex in Reversal-Impaired Aged Rats

Previous work in rats and primates has shown that normal aging can be associated with a decline in cognitive flexibility mediated by prefrontal circuits. For example, aged rats are impaired in rapid reversal learning, which in young rats depends critically on the orbitofrontal cortex. To assess whether aging-related reversal impairments reflect orbitofrontal dysfunction, we identified aged rats with reversal learning deficits and then recorded single units as these rats, along with unimpaired aged cohorts and young control rats, learned and reversed a series of odor discrimination problems. We found that the flexibility of neural correlates in orbitofrontal cortex was markedly diminished in aged rats characterized as reversal-impaired in initial training. In particular, although many cue-selective neurons in young and aged-unimpaired rats reversed odor preference when the odor-outcome associations were reversed, cue-selective neurons in reversal-impaired aged rats did not. In addition, outcome-expectant neurons in aged-impaired rats failed to become active during cue sampling after learning. These altered features of neural encoding could provide a basis for cognitive inflexibility associated with normal aging.

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Functional heterogeneity within the rodent lateral orbitofrontal cortex dissociates outcome devaluation and reversal learning deficits

eLife ◽

10.7554/elife.37357 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 14

Author(s):

Marios C Panayi ◽

Simon Killcross

Keyword(s):

Reversal Learning ◽

Orbitofrontal Cortex ◽

Functional Heterogeneity ◽

Learning Deficits ◽

Sign Tracking ◽

Specific Effects ◽

Instrumental Action ◽

Outcome Devaluation ◽

Human Primate

The orbitofrontal cortex (OFC) is critical for updating reward-directed behaviours flexibly when outcomes are devalued or when task contingencies are reversed. Failure to update behaviour in outcome devaluation and reversal learning procedures are considered canonical deficits following OFC lesions in non-human primates and rodents. We examined the generality of these findings in rodents using lesions of the rodent lateral OFC (LO) in instrumental action-outcome and Pavlovian cue-outcome devaluation procedures. LO lesions disrupted outcome devaluation in Pavlovian but not instrumental procedures. Furthermore, although both anterior and posterior LO lesions disrupted Pavlovian outcome devaluation, only posterior LO lesions were found to disrupt reversal learning. Posterior but not anterior LO lesions were also found to disrupt the attribution of motivational value to Pavlovian cues in sign-tracking. These novel dissociable task- and subregion-specific effects suggest a way to reconcile contradictory findings between rodent and non-human primate OFC research.

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Neural correlates of rapid reversal learning in a simple model of human social interaction

NeuroImage ◽

10.1016/s1053-8119(03)00393-8 ◽

2003 ◽

Vol 20 (2) ◽

pp. 1371-1383 ◽

Cited By ~ 188

Author(s):

Morten L Kringelbach ◽

Edmund T Rolls

Keyword(s):

Social Interaction ◽

Simple Model ◽

Reversal Learning ◽

Neural Correlates ◽

Rapid Reversal

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Serotonergic Innervations of the Orbitofrontal and Medial-prefrontal Cortices are Differentially Involved in Visual Discrimination and Reversal Learning in Rats

Cerebral Cortex ◽

10.1093/cercor/bhaa277 ◽

2020 ◽

Author(s):

Johan Alsiö ◽

Olivia Lehmann ◽

Colin McKenzie ◽

David E Theobald ◽

Lydia Searle ◽

...

Keyword(s):

Prefrontal Cortex ◽

Cognitive Flexibility ◽

Reversal Learning ◽

Orbitofrontal Cortex ◽

Visual Discrimination ◽

Initial Training ◽

Evolutionarily Conserved ◽

Flexible Behavior ◽

Reward Contingencies ◽

To Receive

Abstract Cross-species studies have identified an evolutionarily conserved role for serotonin in flexible behavior including reversal learning. The aim of the current study was to investigate the contribution of serotonin within the orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) to visual discrimination and reversal learning. Male Lister Hooded rats were trained to discriminate between a rewarded (A+) and a nonrewarded (B−) visual stimulus to receive sucrose rewards in touchscreen operant chambers. Serotonin was depleted using surgical infusions of 5,7-dihydroxytryptamine (5,7-DHT), either globally by intracebroventricular (i.c.v.) infusions or locally by microinfusions into the OFC or mPFC. Rats that received i.c.v. infusions of 5,7-DHT before initial training were significantly impaired during both visual discrimination and subsequent reversal learning during which the stimulus–reward contingencies were changed (A− vs. B+). Local serotonin depletion from the OFC impaired reversal learning without affecting initial discrimination. After mPFC depletion, rats were unimpaired during reversal learning but slower to respond at the stimuli during all the stages; the mPFC group was also slower to learn during discrimination than the OFC group. These findings extend our understanding of serotonin in cognitive flexibility by revealing differential effects within two subregions of the prefrontal cortex in visual discrimination and reversal learning.

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Orbitofrontal cortex damage effects in humans and other primates

The Orbitofrontal Cortex ◽

10.1093/oso/9780198845997.003.0004 ◽

2019 ◽

pp. 130-144

Author(s):

Edmund T. Rolls

Keyword(s):

Social Behavior ◽

Reversal Learning ◽

Orbitofrontal Cortex ◽

Food Choice ◽

Rapid Reversal

Impairments in the rapid reversal learning of stimulus-reward associations, when expected rewards are not obtained or punishers are obtained, are produced by damage to the orbitofrontal cortex; and contribute to the major changes in emotion, personality, and impulsiveness that can be produced by damage to the orbitofrontal cortex. Impairments in the processing of rewards are found, with alterations in food choice and eating, and in the identification of face and voice expressions, which are important for social behavior.

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