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Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission
Abstract
The mesolimbic dopamine system is centrally involved in reward and goal-directed behavior, and it has been implicated in multiple psychiatric disorders. Understanding the mechanism by which dopamine participates in these activities requires comprehension of the dynamics of dopamine release. Here we report dissociable regulation of dopamine neuron discharge by two separate afferent systems in rats; inhibition of pallidal afferents selectively increased the population activity of dopamine neurons, whereas activation of pedunculopontine inputs increased burst firing. Only the increase in population activity increased ventral striatal dopamine efflux. After blockade of dopamine reuptake, however, enhanced bursting increased dopamine efflux three times more than did enhanced population activity. These results provide insight into multiple regulatory systems that modulate dopamine system function: burst firing induces massive synaptic dopamine release, which is rapidly removed by reuptake before escaping the synaptic cleft, whereas increased population activity modulates tonic extrasynaptic dopamine levels that are less influenced by reuptake.
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“Burst firing in dopaminergic neurons is potently driven by the brainstem pedunculopontine tegmentum (PPTg), which provides a glutamatergic input that acts via NMDARs ([39, 40] see Box 3).”
From A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP (2011) · cites this paper as [39]
In the citing paper
“The PPTg regulates burst firing of dopamine cells rather than their tonic resting activity [[39]].”
From A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP (2011) · cites this paper as [39]
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Metadata
- Authors
- Floresco, S. B., West, A. R., Ash, B., Moore, H., & Grace, A. A.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Floresco, Stan B
- Grace, Anthony A
- Venue
- Nature Neuroscience
- Published
- 2003-08-03
- Volume
- 6
- Issue
- 9
- Pages
- 968-973
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W1994984635
- Cited by
- 1,106
- References
- 40
- Citations by year
- 2026: 23 · 2025: 33 · 2024: 37 · 2023: 33 · 2022: 49 · 2021: 43 · 2020: 46 · 2019: 50 · 2018: 67 · 2017: 44 · 2016: 61 · 2015: 54 · 2014: 73 · 2013: 55 · 2012: 60
- FWCI
- 13.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (F32MH011305)
- 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
- dopaminergic neurons, mesolimbic dopamine system, pedunculopontine nucleus, burst firing, tonic dopamine release, dopamine reuptake, ventral striatum, dopamine efflux, population activity, reward
- MeSH terms
- Afferent Pathways, Animals, Dopamine, Male, Mesencephalon, Synaptic Transmission, Neurons, Nucleus Accumbens, Rats, Sprague-Dawley, Ventral Tegmental Area, GABA Antagonists, Rats
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