Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning

Tsai, Hsing-Chen; Zhang, Feng; Adamantidis, Antoine; Stuber, Garret D.; Bonci, Antonello; Lecea, Luı́s de; Deisseroth, Karl

doi:10.1126/science.1168878

Cited by 1,099 publications

(1,069 citation statements)

References 28 publications

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“…Thus the stimulation counteracted the negative prediction error induced by the absence of expected reward and thereby conditioned behaviour was sustained. These findings support and extend previous optogenetic studies that implicated dopamine in learning by showing that dopamine neurons code reward prediction errors (Cohen et al, 2012), and that their activation is sufficient to reinforce intracranial self-stimulation (Kim et al, 2012;Rossi et al, 2013;Witten et al, 2011) and leads to conditioned place preference (Tsai et al, 2009) whereas inhibiting them causes avoidance learning (Tan et al, 2012).…”

Section: Causal Role Of (Dopamine-mediated) Prediction Errors In Learsupporting

confidence: 88%

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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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Section: Causal Role Of (Dopamine-mediated) Prediction Errors In Learsupporting

confidence: 88%

“…Most addictive drugs have rapid effects and impact the dopaminergic system either directly or indirectly (Koob, 1992;Olds, 1956;Tsai et al, 2009). Several features of addiction are at least partially amenable to explanations within the overall framework outlined above.…”

Section: Addictionmentioning

confidence: 99%

The role of learning-related dopamine signals in addiction vulnerability

Huys

Tobler

Hasler

et al. 2014

Progress in Brain Research

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“…If animals learn that distinct environmental stimuli reliably predict the delivery of food then these stimuli, (cues) will drive dopamine neuron firing and dopamine release [9,11,36]. In fact, reward-evoked increases in dopamine seem essential for associative learning and reinforcement to take place [78,79].…”

Section: Role Of Taste and Post-ingestive Signals In Reinforcement Anmentioning

confidence: 99%

The role of dopamine in the pursuit of nutritional value

McCutcheon

2015

Physiology & Behavior

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Acquiring enough food to meet energy expenditure is fundamental for all organisms. Thus, mechanisms have evolved to allow foods with high nutritional value to be readily detected, consumed, and remembered. Although taste is often involved in these processes, there is a wealth of evidence supporting the existence of taste-independent nutrient sensing. In particular, post-ingestive mechanisms arising from the arrival of nutrients in the gut are able to drive food intake and behavioural conditioning. The physiological mechanisms underlying these effects are complex but are believed to converge on mesolimbic dopamine signalling to translate post-ingestive sensing of nutrients into reward and reinforcement value. Discerning the role of nutrition is often difficult because food stimulates sensory systems and post-ingestive pathways in concert. Thus, in this mini-review, I discuss the various methods that may be used to study post-ingestive processes in isolation including sham-feeding, nonnutritive sweeteners, post-ingestive infusions, and pharmacological and genetic methods. Using this structure, I present the evidence that dopamine is sensitive to nutritional value of certain foods and examine how this affects learning about food, the role of taste, and the implications for human obesity.

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“…Thus, this suggests that two mechanisms, dopaminergic and glu- to initiate conditioned place preference similar to that of behavioral training [28] . Moreover, phasic activation of VTA dopaminergic neurons leads to a positive reinforcement in food-seeking operant tasks, which is absent when there is no food reward in behavioral training.…”

Section: Ventral Tegmental Area (Vta)mentioning

confidence: 84%

Optogenetics in neuroscience: what we gain from studies in mammals

Chen

Zeng

2012

Neurosci. Bull.

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Abstract:Optogenetics is a newly-introduced technology in the life sciences and is gaining increasing attention. It refers to the combination of optical technologies and genetic methods to control the activity of specific cell groups in living tissue, during which high-resolution spatial and temporal manipulation of cells is achieved. Optogenetics has been applied to numerous regions, including cerebral cortex, hippocampus, ventral tegmental area, nucleus accumbens, striatum, spinal cord, and retina, and has revealed new directions of research in neuroscience and the treatment of related diseases. Since optogenetic tools are controllable at high spatial and temporal resolution, we discuss its applications in these regions in detail and the recent understanding of higher brain functions, such as reward-seeking, learning and memory, and sleep.Further, the possibilities of improved utility of this newly-emerging technology are discussed. We intend to provide a paradigm of the latest advances in neuroscience using optogenetics.

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Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning

Cited by 1,099 publications

References 28 publications

The role of learning-related dopamine signals in addiction vulnerability

The role of learning-related dopamine signals in addiction vulnerability

The role of dopamine in the pursuit of nutritional value

Optogenetics in neuroscience: what we gain from studies in mammals

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