The role of the dorsomedial striatum in instrumental conditioning

Yin, Henry H.; Ostlund, Sean B.; Knowlton, Barbara J.; Balleine, Bernard W.

doi:10.1111/j.1460-9568.2005.04218.x

Cited by 922 publications

(952 citation statements)

References 42 publications

(56 reference statements)

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“…The striatum has been shown to be an important region for specific types of acquisition and memory consolidation, most notably learning involving habituated activity such as lever pressing (Yin et al, 2005). As stated previously, 5-HT 6 receptors are localized in medium spiny GABAergic neurons expressing enkephalin, substance P, and dynorphin receptor subtypes (Ward and Dorsa, 1996).…”

Section: Discussionmentioning

confidence: 76%

Increased Expression of 5-HT6 Receptors in the Rat Dorsomedial Striatum Impairs Instrumental Learning

Mitchell

Sexton

Neumaier

2006

Neuropsychopharmacol

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A number of studies have shown that systemic 5-HT 6 receptor antagonists can improve learning and memory, but the mechanism for these observations is not known. As striatum normally expresses 5-HT 6 receptors abundantly and is important in consolidating stimulusresponse learning, we used targeted gene delivery to further increase the expression of 5-HT 6 receptors in rat striatum and then examined learning. Increased 5-HT 6 expression had no effect on performance in the Morris water maze, a hippocampal-dependent learning paradigm, and did not alter the latency to approach or consume sucrose tablets. However, rats with increased 5-HT 6 expression failed to acquire a reward-based instrumental learning task, a striatum-dependent learning model, during 3 days of successive sessions as compared to sham surgery or GFP-expressing control rats. This behavioral deficit was observed in rats overexpressing 5-HT 6 receptors in the dorsomedial striatum, but not in rats with increased dorsocentral striatal expression. The 5-HT 6 receptor-associated deficit was reversed by administration of a 5-HT 6 antagonist, SB-258585, before each training session. When animals learned the instrumental learning task before gene transfer, increased 5-HT 6 receptor expression had no effect on long-term recall or performance of the task or on extinction of operant responding. Thus, 5-HT 6 receptor activity in rat striatum disrupts acquisition of new instrumental learning but does not impair memory or performance of reward-motivated behavior once established.

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Section: Discussionmentioning

confidence: 76%

Increased Expression of 5-HT6 Receptors in the Rat Dorsomedial Striatum Impairs Instrumental Learning

Mitchell

Sexton

Neumaier

2006

Neuropsychopharmacol

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“…By arguing that goal-trackers are indeed more goal-directed, this suggests the involvement of goaldirected neural structures (Yin et al, 2004(Yin et al, , 2005O'Doherty et al, 2004;Killcross and Coutureau, 2003). In agreement, goal-trackers do seem to recruit cortical "top-down" regulation of their response to reward-cues (Flagel et al, 2011a).…”

Section: Goal-trackersmentioning

confidence: 88%

The role of learning-related dopamine signals in addiction vulnerability

Huys

Tobler

Hasler

et al. 2014

Progress in Brain Research

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Psychostimulants such as methylphenidate (MPH) and antidepressants such as fluoxetine (FLX) are widely used in the treatment of various mental disorders or as cognitive enhancers. These medications are often combined, for example, to treat comorbid disorders. There is a considerable body of evidence from animal models indicating that individually these psychotropic medications can have detrimental effects on the brain and behavior, especially when given during sensitive periods of brain development. However, almost no studies investigate possible interactions between these drugs. This is surprising given that their combined neurochemical effects (enhanced dopamine and serotonin neurotransmission) mimic some effects of illicit drugs such as cocaine and amphetamine. Here, we summarize recent studies in juvenile rats on the molecular effects in the mid-and forebrain and associated behavioral changes, after such combination treatments. Our findings indicate that these combined MPH + FLX treatments can produce similar molecular changes as seen after cocaine exposure while inducing behavioral changes indicative of dysregulated mood and motivation, effects that often endure into adulthood. Tables: 2 References: 254 ABSTRACT Dopaminergic signals play a mathematically precise role in reward-related learning, and variations in dopaminergic signalling have been implicated in vulnerability to addiction. Here, we provide a detailed overview of the relationship between theoretical, mathematical and experimental accounts of phasic dopamine signalling, with implications for the role of learning-related dopamine signalling in addiction and related disorders. We describe the theoretical and behavioural characteristics of model-free learning based on errors in the prediction of reward, including step-by-step explanations of the underlying equations. We then use recent insights from an animal model that highlights individual variation in learning during a Pavlovian conditioning paradigm to describe overlapping aspects of incentive salience attribution and model-free learning. We argue that this provides a computationally coherent account of some features of addiction. CONTENTS

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“…Lesions or inactivations of all three areas have been found to cause impairments in devaluation and in a task in which knowledge about the contingencies associated with two lever-reward contingencies is tested (Balleine & Dickinson, 1998;Killcross & Coutureau, 2003;Yin, Ostlund, Knowlton, & Balleine, 2005), as well as in strategy set shifting (Block et al, 2007;Ragozzino, Detri ck, & Kesner, 1999;Ragozzino, Ragozzino, Mizumori, & Kesner, 2002). This suggests that the role of this loop may be in suppressing old associations so that new associations can be learned in tasks with new contingencies or responses, and that this can account for previous findings that have suggested a role for this circuit in "goal-directed action".…”

Section: Discussionmentioning

confidence: 99%

A limited role for mediodorsal thalamus in devaluation tasks.

Pickens

2008

Behavioral Neuroscience

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Six experiments were performed to determine the role of mediodorsal thalamus (MD) in the devaluation task, varying the type of contingencies (Pavlovian or operant), the number of reinforcers (one versus two) and the order of experiments (in naïve or experimentally experienced rats). MD lesioned rats were impaired in devaluation performance when switched between Pavlovian and operant devaluation tasks, but not when switched from one Pavlovian devaluation task to another Pavlovian devaluation task. MD lesions caused no devaluation impairment in a multiple reinforcer Pavlovian devaluation task. These results suggest that MD lesions impair performance in devaluation tasks as a result of an inability to switch the form of associations made from one type of outcome-encoding association to another. This is in accord with previous literature suggesting that MD is needed for strategy set shifting. The results further suggest that MD is a necessary part of devaluation circuits only in cases in which previous associations need to be suppressed in order for new associations to be learned and control behavior, and otherwise the devaluation circuit does not require MD. KeywordsMediodorsal thalamus; devaluation; set-shifting; reward Devaluation tasks involve training a relationship that earns or predicts a valuable outcome, such as a lever press that earns a type of food or a light that predicts the delivery of food (Adams & Dickinson, 1981;Holland & Rescorla, 1975). The value of this outcome is then reduced by motivational (e.g., satiation) or associative methods (e.g., a food aversion is established by food-toxin pairings). After such outcome devaluation, responding based on the relationship that predicts or earns food is typically reduced. Similarities in task demands to human decision making, as well as similarities in neural underpinnings, suggests that the devaluation task provides a model of goal expectancy-guided behavior (as reviewed in Pickens & Holland, 2004).Many reports have examined the neural circuitry involved in acting according to the current value of goals. For example, lesions of amygdala, or specific lesions of basolateral complex of amygdala (BLA), cause impairments in many versions of the devaluation task (Balleine, Killcross, & Dickinson, 2003;Blundell, Hall & Killcross, 2003;Hatfield, Han, Conley, Gallagher, & Holland, 1996;Malkova, Gaffan & Murray, 1997). Several laboratories have also found that bilateral orbitofrontal cortex (OFC) lesions (Gallagher, McMahan & Schoenbaum, 1999;Izquierdo, Suda & Murray, 2004; but see Ostlund & Balleine, 2007) or lesions that disconnect amygdala and OFC (Baxter, Parker, Lindner, Izquierdo, & Murray, 2000) impair performance in devaluation tasks. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAnother brain area that may be needed for devaluation is mediodorsal thalamus (MD). MD, BLA and OFC are all interconnected (Carmichael & Price, 1995;Ghashghaei & Barbas, 2002;Groenewegen, 1988;Ray & Price, 1992) and the three brain areas share s...

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The role of the dorsomedial striatum in instrumental conditioning

Cited by 922 publications

References 42 publications

Increased Expression of 5-HT6 Receptors in the Rat Dorsomedial Striatum Impairs Instrumental Learning

Increased Expression of 5-HT6 Receptors in the Rat Dorsomedial Striatum Impairs Instrumental Learning

The role of learning-related dopamine signals in addiction vulnerability

A limited role for mediodorsal thalamus in devaluation tasks.

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