Paradoxical reversal learning enhancement by stress or prefrontal cortical damage: rescue with BDNF

Abstract

Stress often has deleterious effects on cognition. We show that moderate stress enhanced late reversal learning in a mouse touchscreen-based choice task. Ventromedial prefrontal cortex (vmPFC) lesions mimicked the effects of stress, while orbitofrontal (OFC) and dorsolateral striatal (DLS) lesions impaired reversal. Stress-facilitation of reversal was prevented by BDNF infusion into the vmPFC. These findings suggest a mechanism in which stress-induced vmPFC dysfunction disinhibits learning by alternate (e.g., striatal) systems.

Stress facilitates late reversal learning using a touchscreen-based visual discrimination procedure in male Long Evans rats

“…No immediate effects of stress were found on the early phase of reversal learning during which perseveration is high; however, late reversal learning (>50% correct) was facilitated in C57BL/6J mice subjected to the stressor [11] but not those from the DBA/2J strain [12]. The facilitation of reversal learning was prevented by BDNF infusions into the ventromedial PFC and mimicked by lesions of the same region [11]. In contrast, Thai and colleagues used an operant-based spatial reversal learning task in rats that took one session to complete [10].…”

“…After being trained on a discrimination task for food reward and before initiating a reversal of the discrimination, mice were subjected to 3 days of swim stress. No immediate effects of stress were found on the early phase of reversal learning during which perseveration is high; however, late reversal learning (>50% correct) was facilitated in C57BL/6J mice subjected to the stressor [11] but not those from the DBA/2J strain [12]. The facilitation of reversal learning was prevented by BDNF infusions into the ventromedial PFC and mimicked by lesions of the same region [11].…”

“…However, the influence of acute stress on forms of cognition dependent on prefrontal cortex (PFC) is less well defined [1]. Research regarding the influence of acute stress on PFC-dependent executive processing and cognitive/behavioral flexibility have been inconsistent, with some studies showing impaired performance [6][7][8][9] while others show facilitated performance [10][11][12][13][14], depending on the specific task and stressor.…”

“…Reversal learning, a type of behavioral flexibility that requires a change in strategy based on one dimension of the stimuli, is partly mediated by the orbitofrontal cortex [11,16]. Reversal learning assayed using operant-based tasks is facilitated following an acute (1 day) or subchronic (3 days) stressor in most [10][11][12] but not all studies [7].…”

“…Previous studies have used two operant paradigms for assessing the effects of acute stress on reversal learning. In two studies [11,12], a touchscreen-based discrimination task [17][18][19] that took several weeks to complete was used in mice. After being trained on a discrimination task for food reward and before initiating a reversal of the discrimination, mice were subjected to 3 days of swim stress.…”