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Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning
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Rewarding Bursts of Dopamine: Dopaminergic neurons are thought to be involved in the cognitive and hedonic underpinnings of motivated behaviors. However, it is still unclear whether dopaminergic neuron activation is sufficient to elicit reward-related behavior and which type of neuronal activity pattern serves this purpose. Tsai et al. (p. 1080; published online 23 April) directly compared tonic versus phasic firing of dopaminergic cells in the ventral tegmental area, and the effects on both behavior and dopamine release. Using a transgenic system and virus injection in mice, they targeted the dopaminergic cells with rhodopsin. Light stimulation was then used to drive dopaminergic cells either with a tonic low level of pulses or bursts of high-frequency pulses, with the number of pulses being equal across conditions. Only the high-frequency phasic firing induced a conditioned place preference and dopamine release.
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“There is an increase in DA release (measured in awake, behaving animals by microdialysis or by fastscanning cyclic voltammetry) in the NAc in response to unexpected food rewards or stimuli that predict food rewards [72,308-310].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [72]
In the citing paper
“This evidence was recently further investigated in an animal study using optogenetics, which showed that activation of the VTA leads to dopamine release in the NAc (Tsai et al., 2009; for a review, see Lenz and Lobo, 2013).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Tsai et al., 2009
In the citing paper
“However, since optogenetic activation of VTA DA neurons increases social interaction (Gunaydin et al., 2014) and supports positive reinforcement (Tsai et al., 2009, Witten et al., 2011), they are thought to play a causal role in social reward.”
From Dorsal raphe dopamine neurons represent the experience of social isolation (2016) · cites this paper as Tsai et al., 2009
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“The light activated channelrhodopsin (ChR2) (19, 20) has been used in other neural systems to activate specific cell populations and produce learning (21–23).”
From Optical activation of lateral amygdala pyramidal cells instructs associative fear learning (2010) · cites this paper as [21]
In the citing paper
“conversely, simulating burst firing using channelrhodopsin is sufficient to induce behavioral conditioning [42].”
From A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP (2011) · cites this paper as [42]
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Metadata
- Authors
- Tsai, H.-C., Zhang, F., Adamantidis, A., Stuber, G. D., Bonci, A., de Lecea, L., & Deisseroth, K.
- Affiliations
- Stanford University (US)
- University of California, San Francisco (US)
- Department of Psychiatry and Behavioral Sciences, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, CA 94305, USA.
- Corresponding author
- Tsai, Hsing-Chen
- Zhang, Feng
- Deisseroth, Karl
- ORCID
- Venue
- Science
- Published
- 2009-05-22
- Volume
- 324
- Issue
- 5930
- Pages
- 1080-1084
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5262197
- OpenAlex
- W1980737345
- Cited by
- 1,266
- References
- 28
- Citations by year
- 2026: 31 · 2025: 53 · 2024: 63 · 2023: 51 · 2022: 68 · 2021: 58 · 2020: 74 · 2019: 68 · 2018: 74 · 2017: 92 · 2016: 90 · 2015: 99 · 2014: 105 · 2013: 87 · 2012: 82
- FWCI
- 34.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH087592)
- National Institute on Drug Abuse (R01DA021880)
- National Institute of Neurological Disorders and Stroke (K99NS065009)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- phasic firing, dopaminergic neurons, ventral tegmental area, behavioral conditioning, optogenetic stimulation, natural reward, drugs of abuse
- MeSH terms
- Channelrhodopsins, Action Potentials, Animals, Behavior, Animal, Conditioning, Psychological, Dopamine, Electrodes, Implanted, Genetic Vectors, Light, Mice, Transgenic, Neurons, Reward, Transduction, Genetic, Ventral Tegmental Area, Patch-Clamp Techniques, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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