Selective lesions of the dorsomedial striatum impair serial spatial reversal learning in rats

Abstract

Impairments in reversal learning have been attributed to orbitofrontal cortex (OFC) dysfunction in many species. However, the role of subcortical areas interconnected with the OFC such as the striatum remains poorly understood. This study directly evaluated the contribution of core and shell sub-regions of the nucleus accumbens (NAc), dorsomedial (DMS) and dorsolateral (DLS) striatum to reversal learning of an instrumental two-lever spatial discrimination task in rats. Selective NAc core, DMS and DLS lesions were achieved with microinjections of quinolinic acid and NAc shell lesions with ibotenic acid. Damage to NAc core or shell did not affect retention of a previously acquired instrumental spatial discrimination. In contrast, DLS and DMS lesions produced changes in aspects of discrimination performance such as the latency to collect earned food pellets. Neither NAc core or shell lesions nor DLS lesions affected the main indices of reversal performance. Conversely, DMS lesion rats showed a significant impairment in reversal learning. DMS damage increased the number of errors to reach criteria that were perseverative in nature. The deficit in reversal learning in DMS lesion rats was not associated with an impairment to extinguish instrumental responding. There were no effects on spontaneous locomotor activity. Our data are in agreement with recent work showing that lesions of the medial striatum in marmoset monkeys produce perseverative impairments during a serial visual discrimination reversal task and support the hypothesis that dorsomedial striatal dysfunction contributes to pathological perseveration, which is a common feature of many psychiatric disorders.

Hippocampus and subregions of the dorsal striatum respond differently to a behavioral strategy change on a spatial navigation task

“…Anterior dorsolateral striatum (aDLS) receives input from motor and sensory areas (Alexander and Crutcher 1990;Berendse et al 1992;McGeorge and Faull 1989) and regulates motor control and habit-based behaviors (Carelli and West 1991;Cho and West 1997;Hikosaka et al 1995;Miyachi et al 1997;Smith and Graybiel 2013). Dorsomedial striatum has been implicated as playing a role in goal-directed behavior (Devan et al 1999;Gremel and Costa 2013;Yin et al 2005b;, such as reversal learning (Castañé et al 2010;Kirkby 1969;Ragozzino 2007;Ragozzino and Choi 2004) and changing strategies (Ragozzino 2007;Ragozzino et al 2002aRagozzino et al , 2002b.…”

Blockade of NMDA GluN2B receptors selectively impairs behavioral flexibility but not initial discrimination learning

“…Likewise, treatment with Ro25-6981 on day 1 also did not significantly alter trials to criterion on either a visual cue or response discrimination (all Fs<1.5, n.s.). In contrast, analyses of the number of errors [which is one of the most sensitive measures of animals' performance on discrimination and strategy shift/reversal tasks (Castañé et al 2010)] did reveal significant effects of treatment. For each experiment, error data were analyzed using two-way ANOVAs, with treatment (vehicle or drug) as the betweensubjects factor and error type as a within-subjects factor.…”

Markers of Serotonergic Function in the Orbitofrontal Cortex and Dorsal Raphé Nucleus Predict Individual Variation in Spatial-Discrimination Serial Reversal Learning

“…However, despite these biphasic effects, we found no differences between high-and low-perseverative animals in levels of DA or its metabolite DOPAC in the DMS. Striatal mechanisms have previously been linked to behavioral flexibility through selective lesion studies (Castane et al, 2010) and local DA depletion (Clarke et al, 2011;O'Neill and Brown, 2007), which have the common effect of impairing reversal learning. Striatal DA levels have also been shown to predict performance on outcome-specific reversal-learning tasks (Clatworthy et al, 2009;Cools et al, 2009).…”

“…In rats, 5-HT 2A and 5-HT 2C receptors bidirectionally modulate reversal learning (Boulougouris et al, 2008), putatively at the level of the OFC (Boulougouris and Robbins, 2010). Research also links the DMS and its DA, but not 5-HT, innervation to reversal learning (Castane et al, 2010;Clarke et al, 2011;O'Neill and Brown, 2007). Optimal DA levels in the striatum are associated with improved reversal learning (Clatworthy et al, 2009;Cools et al, 2009), and in nonhuman primates flexible behavior depends in part on 5-HT and DA interactions in the OFC and striatum (Groman et al, 2013).…”