The Contribution of the Medial Prefrontal Cortex, Orbitofrontal Cortex, and Dorsomedial Striatum to Behavioral Flexibility

Abstract

Behavioral flexibility refers to the ability to shift strategies or response patterns with a change in environmental contingencies. The frontal lobe and basal ganglia are two brain regions implicated in various components for successfully adapting to changed environmental contingencies. This paper discusses a series of experiments that investigate the contributions of the rat prelimbic area, infralimbic area, orbitofrontal cortex, and dorsomedial striatum to behavioral flexibility. Orbitofrontal cortex inactivation did not impair initial learning of discrimination tests, but it impaired reversal learning due to perseverance in the previously learned choice pattern. Inactivation of the prelimbic area did not affect acquisition or reversal learning of different discrimination tests, but it selectively impaired learning when rats had to inhibit one strategy and shift to using a new strategy. However, comparable to orbitofrontal cortex inactivation, strategy-switching deficits following prelimbic inactivation resulted from a perseverance of the previously relevant strategy. Fewer studies have examined the infralimbic region, but there is some evidence suggesting that this region supports reversal learning by maintaining the reliable execution of a new choice pattern. Dorsomedial striatal inactivation impaired both reversal learning and strategy switching. The behavioral flexibility deficits following dorsomedial striatal inactivation resulted from the inability to maintain a new choice pattern once selected. Taken together, the results suggest that orbitofrontal and prelimbic subregions differentially contribute to behavioral flexibility, but they are both critical for the initial inhibition of a previously learned strategy, while the dorsomedial striatum plays a broader role in behavioral flexibility and supports a process that allows the reliable execution of a new strategy once selected.

The Dorsomedial Striatum Reflects Response Bias during Learning

“…Lesions of the dorsomedial striatum impair initial reversal learning, but not discrimination learning (Kirkby, 1969;Pisa and Cyr, 1990;Adams et al, 2001;Ragozzino et al, 2002;Palencia and Ragozzino, 2004;Featherstone and McDonald, 2005;Broadbent et al, 2007;Ragozzino, 2007). Based on these studies, we hypothesized that neurons in the dorsomedial striatum would show major changes in task-related activity (such as selective firing during Go or NoGo responding, as in the study by ) during reversal learning, but not during Go/NoGo learning.…”

“…Both of these cortical regions project to the dorsomedial striatum (McGeorge and Faull, 1989;Berendse et al, 1992;Cheatwood et al, 2003Cheatwood et al, , 2005. Moreover, differences in reversal behavior have been noted following lesions of the cortex and striatum (Dube et al, 1996;Ragozzino, 2007;Ragozzino and Rozman, 2007;Clarke et al, 2008), with cortical lesions having pronounced effects early in a reversal. These studies support the idea that orbitofrontal neurons represent the current value of a stimulus based on a comparison between expected and obtained outcomes (Schoenbaum et al, 2007).…”

Ventral Striatal Dopamine Modulation of Different Forms of Behavioral Flexibility

“…The present results suggest that dopaminergic modulation of reversal learning likely occurs through actions on D 2 receptors located in regions other than the NAc. In this regard, although the OFC is critical in facilitating reversal shifts (Dias et al, 1996;McAlonan and Brown, 2003;Ragozzino, 2007;Ghods-Sharifi et al, 2008), mesocortical DA depletion does not affect this form of flexibility (Crofts et al, 2001). The possibility remains that the certain subregions of the dorsal striatum may be the critical locus where D 2 receptors enable shifts between different stimulus-reward contingencies, although striatal DA depletion has yielded inconsistent effects on reversal learning (Collins et al, 2000;Crofts et al, 2001;O'Neill and Brown, 2007).…”

Neurotoxic lesions of the thalamic reuniens or mediodorsal nucleus in rats affect non-mnemonic aspects of watermaze learning

“…Later studies revealed that mPFC lesions can also cause no impairment in spatial navigation, but rather result in a deficit of behavioural flexibility (De Bruin et al 1994, 2001Lacroix et al 2002). In various tests, it has been shown that destruction or inactivation of mPFC does not affect learning and memory per se, but impairs the animals' ability to shift strategy, or rule out inappropriate strategies when task demands are changed or environmental conditions are altered (Ragozzino et al 1999a, b;Delatour and Gisquet-Verrier 2000;Dias and Aggleton 2000;Lacroix et al 2002;Sullivan and Gratton 2002;Passetti et al 2002;Ragozzino et al 2003;Ragozzino 2007). At first sight, in relation to RE-mPFC connectivity, these reports seem contradictory to the rapid strategy shifting by RE-rats.…”