Dynamic Nigrostriatal Dopamine Biases Action Selection

Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action sel...

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Veröffentlicht in:Neuron (Cambridge, Mass.) Mass.), 2017-03, Vol.93 (6), p.1436-1450.e8
Hauptverfasser: Howard, Christopher D., Li, Hao, Geddes, Claire E., Jin, Xin
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Li, Hao
Geddes, Claire E.
Jin, Xin
description Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn’t reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons or optogenetic manipulation of dopamine concentration alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions, and they have important implications for neurological disorders, including Parkinson’s disease and substance dependence. •Nigrostriatal dopamine signaling is associated with ongoing action selection•Dopamine signaling is necessary for appropriate action selection•Optogenetic manipulations can bidirectionally modulate online action selection•Modeling suggests dopamine could bias choice by modifying striatal activity Howard et al. recorded nigrostriatal dopamine signaling while animals dynamically altered their actions to retrieve rewards. They found that dopamine signaling is associated with action selection and that modulating dopamine biases the online action selection processes.
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Here we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn’t reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons or optogenetic manipulation of dopamine concentration alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions, and they have important implications for neurological disorders, including Parkinson’s disease and substance dependence. •Nigrostriatal dopamine signaling is associated with ongoing action selection•Dopamine signaling is necessary for appropriate action selection•Optogenetic manipulations can bidirectionally modulate online action selection•Modeling suggests dopamine could bias choice by modifying striatal activity Howard et al. recorded nigrostriatal dopamine signaling while animals dynamically altered their actions to retrieve rewards. 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Here we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn’t reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons or optogenetic manipulation of dopamine concentration alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions, and they have important implications for neurological disorders, including Parkinson’s disease and substance dependence. •Nigrostriatal dopamine signaling is associated with ongoing action selection•Dopamine signaling is necessary for appropriate action selection•Optogenetic manipulations can bidirectionally modulate online action selection•Modeling suggests dopamine could bias choice by modifying striatal activity Howard et al. recorded nigrostriatal dopamine signaling while animals dynamically altered their actions to retrieve rewards. They found that dopamine signaling is associated with action selection and that modulating dopamine biases the online action selection processes.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28285820</pmid><doi>10.1016/j.neuron.2017.02.029</doi><oa>free_for_read</oa></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals Complete; Cell Press Free Archives; EZB-FREE-00999 freely available EZB journals
subjects action selection
Addictive behaviors
Animals
basal ganglia
Behavior
Caudate-putamen
conditional knockout
Conditioning, Operant - physiology
Corpus Striatum - physiology
Decision making
direct and indirect pathway
Dopamine
Dopamine - metabolism
Dopaminergic Neurons - physiology
electrophysiology
fast-scan cyclic voltammetry
Female
Firing rate
Glutamic acid receptors (ionotropic)
Male
Mice
Mice, Knockout
Mice, Transgenic
N-Methyl-D-aspartic acid receptors
Neostriatum
network model
Neural Pathways - physiology
Neurological diseases
Neurons
Neurosciences
optogenetics
Receptors, N-Methyl-D-Aspartate - genetics
Receptors, N-Methyl-D-Aspartate - physiology
Reinforcement
Reward
striatum
Substantia Nigra - physiology
Voltammetry
title Dynamic Nigrostriatal Dopamine Biases Action Selection
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