Cited by 183Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

Midbrain dopamine neurons bidirectionally regulate CA3-CA1 synaptic drive

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Rosen, Zev B, Cheung, Stephanie, Siegelbaum, Steven A·2015·Nature Neuroscience

Abstract

Dopamine (DA) is required for hippocampal-dependent memory and long-term potentiation (LTP) at CA1 Schaffer collateral (SC) synapses. It is therefore surprising that exogenously applied DA has little effect on SC synapses, but suppresses CA1 perforant path (PP) inputs. To examine DA actions under more physiological conditions, we used optogenetics to release DA from ventral tegmental area inputs to hippocampus. Unlike exogenous DA application, optogenetic release of DA caused a bidirectional, activity-dependent modulation of SC synapses, with no effect on PP inputs. Low levels of DA release, simulating tonic DA neuron firing, depressed the SC response through a D4 receptor-dependent enhancement of feedforward inhibition mediated by parvalbumin-expressing interneurons. Higher levels of DA release, simulating phasic firing, increased SC responses through a D1 receptor-dependent enhancement of excitatory transmission. Thus, tonic-phasic transitions in DA neuron firing in response to motivational demands may cause a modulatory switch from inhibition to enhancement of hippocampal information flow.

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  • Our results confirm recent studies using viral expression of channelrhodopsin in Slc6a3ires-cre/+ mice that labeled relatively sparse dopaminergic axons in the CA1 region.

    “Our results also confirm recent studies using viral expression of channelrhodopsin in Slc6a3ires-cre/+ mice that labeled relatively sparse dopaminergic axons in the CA1 region (McNamara et al., 2014; Rosen et al., 2015).”
  • Optogenetic release of dopamine exclusively from the VTA causes a bidirectional, activity-dependent modulation of Schaffer collateral synapses in hippocampal slices.

    “In addition, optogenetic release of dopamine exclusively from the VTA was shown to cause a bidirectional, activity-dependent modulation of Schaffer collateral synapses in hippocampal slices (Rosen et al., 2015).”
  • Despite the sparse innervation of the hippocampus by midbrain dopaminergic axons, several lines of evidence indicate a significant functional role for this dopaminergic innervation.

    “Despite the sparse innervation of the hippocampus by midbrain dopaminergic axons, several lines of evidence indicate a significant functional role for this dopaminergic innervation.”

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Authors
Rosen, Z. B., Cheung, S., & Siegelbaum, S. A.
Affiliations
Columbia University (US)
Corresponding author
Siegelbaum, Steven A
Venue
Nature Neuroscience
Published
2015-11-02
Volume
18
Issue
12
Pages
1763-1771
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2184138621
Cited by
183
References
48
Citations by year
2026: 11 · 2025: 21 · 2024: 30 · 2023: 15 · 2022: 16 · 2021: 12 · 2020: 16 · 2019: 11 · 2018: 16 · 2017: 21 · 2016: 13 · 2015: 1
FWCI
10.23
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health
  • National Institute of Mental Health (T32MH015174)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
dopamine, ventral tegmental area, hippocampus, CA1 pyramidal neurons, Schaffer collateral synapses, perforant path, dopamine D1 receptor, dopamine D4 receptor, parvalbumin interneurons, feedforward inhibition, hippocampal-dependent memory, long-term potentiation
MeSH terms
Animals, Dopamine, Mesencephalon, Mice, Inbred C57BL, Mice, Transgenic, Neural Pathways, Synapses, Mice, CA1 Region, Hippocampal, CA3 Region, Hippocampal, Dopaminergic Neurons, Optogenetics

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