Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli
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Midbrain dopamine (DA) neurons are not homogeneous but differ in their molecular properties and responses to external stimuli. We examined whether the modulation of excitatory synapses on DA neurons by rewarding or aversive stimuli depends on the brain area to which these DA neurons project. We identified DA neuron subpopulations in slices after injection of "Retrobeads" into single target areas of adult mice and found differences in basal synaptic properties. Administration of cocaine selectively modified excitatory synapses on DA cells projecting to nucleus accumbens (NAc) medial shell while an aversive stimulus selectively modified synapses on DA cells projecting to medial prefrontal cortex. In contrast, synapses on DA neurons projecting to NAc lateral shell were modified by both rewarding and aversive stimuli, which presumably reflects saliency. These results suggest that the mesocorticolimbic DA system may be comprised of three anatomically distinct circuits, each modified by distinct aspects of motivationally relevant stimuli.
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This subpopulation of DA neurons projects to the medial prefrontal cortex and the medial shell of the nucleus accumbens.
“Anatomically, this subpopulation of DA neurons projects to the medial prefrontal cortex and the medial shell of the nucleus accumbens (Lammel et al., 2011; Lammel et al., 2012).”
From Dopamine regulates aversive contextual learning and associated in vivo synaptic plasticity in the Hippocampus (2016) · cites this paper as Lammel et al., 2011
Aversive events recruit subpopulations of DA neurons to contribute to learning and memory.
“These results support the hypothesis that aversive events recruit subpopulations of DA neurons (Brischoux et al., 2009; Henny et al., 2012; Lammel et al., 2011; Lammel et al., 2014; Lammel et al., 2012) to contribute to learning and memory.”
From Dopamine regulates aversive contextual learning and associated in vivo synaptic plasticity in the Hippocampus (2016) · cites this paper as Lammel et al., 2011
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- Authors
- Lammel, S., Ion, D. I., Roeper, J., & Malenka, R. C.
- Affiliations
- Stanford Medicine (US)
- Goethe University Frankfurt (DE)
- Corresponding author
- Malenka, Robert C.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 70
- Issue
- 5
- Pages
- 855-862
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3112473
- OpenAlex
- W1998939463
- Cited by
- 766
- References
- 68
- Citations by year
- 2026: 30 · 2025: 36 · 2024: 46 · 2023: 48 · 2022: 52 · 2021: 44 · 2020: 44 · 2019: 55 · 2018: 63 · 2017: 57 · 2016: 54 · 2015: 60 · 2014: 64 · 2013: 52 · 2012: 43
- FWCI
- 23.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (P01DA008227)
- 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 › Memory and Neural Mechanisms
- Keywords
- midbrain dopaminergic neurons, excitatory synapses, synaptic modulation, aversive stimuli, nucleus accumbens, medial prefrontal cortex, cocaine, salience, mesocorticolimbic system, motivation
- MeSH terms
- Analysis of Variance, Animals, Bicuculline, Biotin, Cerebral Cortex, Cocaine, Dopamine, Drug Administration Schedule, Electric Stimulation, Male, Mesencephalon, Mice, Inbred C57BL, Mice, Transgenic, Neural Pathways, Neurons, Reward, Substantia Nigra, Synapses, Tyrosine 3-Monooxygenase, 2-Amino-5-phosphonovalerate, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists, Dopamine Uptake Inhibitors, Green Fluorescent Proteins, Mice, Inhibitory Postsynaptic Potentials, GABA-A Receptor Antagonists, In Vitro Techniques
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