Recombinase-Driver Rat Lines: Tools, Techniques, and Optogenetic Application to Dopamine-Mediated Reinforcement

Witten, Ilana B.; Steinberg, Elizabeth E.; Lee, Soo Yeun; Davidson, Thomas J.; Zalocusky, Kelly A.; Brodsky, Matthew; Yizhar, Ofer; Cho, Saemi L.; Gong, Shiaoching; Ramakrishnan, Charu; Stuber, Garret D.; Tye, Kay M.; Janak, Patricia H.; Deisseroth, Karl

doi:10.1016/j.neuron.2011.10.028

Cited by 600 publications

(631 citation statements)

References 62 publications

Supporting

Mentioning

583

Contrasting

Unclassified

Order By: Relevance

“…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%

The role of learning-related dopamine signals in addiction vulnerability

Huys

Tobler

Hasler

et al. 2014

Progress in Brain Research

View full text Add to dashboard Cite

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

show abstract

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

confidence: 88%

The role of learning-related dopamine signals in addiction vulnerability

Huys

Tobler

Hasler

et al. 2014

Progress in Brain Research

View full text Add to dashboard Cite

show abstract

“…The number of transgenic rats and higher mammals, such as cats and monkeys, are highly restricted [39]. While technical advances have made the creation of transgenic rats and larger mammals easier [40], the high cost of creating and maintaining these animals and the large number of mouse transgenic lines makes the mouse the most practical choice for most studies.…”

Section: Genetic Identitymentioning

confidence: 99%

“…Optogenetic manipulation has been used, for example, to alter the firing rate of dopamine neurons in the ventral tegmental area, which is critical for coding reward [125]. The frequency of the light stimulation was critical to how the animal responds to a stimulus, indicating that the firing frequency of this reward circuit is critical to its function [39,125]. This temporal precision allows manipulation of specific neurons or circuits in a time-locked behavior, such as unexpected reward [125,126].…”

Section: Optogeneticsmentioning

confidence: 99%

Selective Manipulation of Neural Circuits

Park

Carmel

2016

Neurotherapeutics

View full text Add to dashboard Cite

Unraveling the complex network of neural circuits that form the nervous system demands tools that can manipulate specific circuits. The recent evolution of genetic tools to target neural circuits allows an unprecedented precision in elucidating their function. Here we describe two general approaches for achieving circuit specificity. The first uses the genetic identity of a cell, such as a transcription factor unique to a circuit, to drive expression of a molecule that can manipulate cell function. The second uses the spatial connectivity of a circuit to achieve specificity: one genetic element is introduced at the origin of a circuit and the other at its termination. When the two genetic elements combine within a neuron, they can alter its function. These two general approaches can be combined to allow manipulation of neurons with a specific genetic identity by introducing a regulatory gene into the origin or termination of the circuit. We consider the advantages and disadvantages of both these general approaches with regard to specificity and efficacy of the manipulations. We also review the genetic techniques that allow gain-and loss-of-function within specific neural circuits. These approaches introduce light-sensitive channels (optogenetic) or drug sensitive channels (chemogenetic) into neurons that form specific circuits. We compare these tools with others developed for circuit-specific manipulation and describe the advantages of each. Finally, we discuss how these tools might be applied for identification of the neural circuits that mediate behavior and for repair of neural connections.

show abstract

“…Importantly, such behaviors can easily be regained by photoactivation of the targeted dopaminergic neurons [29,52] . in intracranial self-stimulation tests [53] . In contrast, optogenetic activation of VTA GABAergic neurons induces an inhibitory response [54,55] .…”

Section: Ventral Tegmental Area (Vta)mentioning

confidence: 99%

Optogenetics in neuroscience: what we gain from studies in mammals

Chen

Zeng

2012

Neurosci. Bull.

View full text Add to dashboard Cite

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.

show abstract

Recombinase-Driver Rat Lines: Tools, Techniques, and Optogenetic Application to Dopamine-Mediated Reinforcement

Cited by 600 publications

References 62 publications

The role of learning-related dopamine signals in addiction vulnerability

The role of learning-related dopamine signals in addiction vulnerability

Selective Manipulation of Neural Circuits

Optogenetics in neuroscience: what we gain from studies in mammals

Contact Info

Product

Resources

About