Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory
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Dopamine neurotransmission in the dorsal hippocampus is critical for a range of functions from spatial learning and synaptic plasticity to the deficits underlying psychiatric disorders such as attention-deficit hyperactivity disorder. The ventral tegmental area (VTA) is the presumed source of dopamine in the dorsal hippocampus. However, there is a surprising scarcity of VTA dopamine axons in the dorsal hippocampus despite the dense network of dopamine receptors. We have explored this apparent paradox using optogenetic, biochemical, and behavioral approaches and found that dopaminergic axons and subsequent dopamine release in the dorsal hippocampus originate from neurons of the locus coeruleus (LC). Photostimulation of LC axons produced an increase in dopamine release in the dorsal hippocampus as revealed by high-performance liquid chromatography. Furthermore, optogenetically induced release of dopamine from the LC into the dorsal hippocampus enhanced selective attention and spatial object recognition via the dopamine D1/D5 receptor. These results suggest that spatial learning and memory are energized by the release of dopamine in the dorsal hippocampus from noradrenergic neurons of the LC. The present findings are critical for identifying the neural circuits that enable proper attention selection and successful learning and memory.
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Stimulation of locus coeruleus neurons enhances hippocampus-dependent memory.
“Notably, stimulation of locus coeruleus neurons, presumably releasing noradrenaline or dopamine, enhances hippocampus-dependent memory [105–108].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [106]
DAergic projections to the dorsal hippocampus originate primarily from the locus coeruleus rather than the ventral tegmental area.
“the DAergic projections to the dorsal hippocampus, which originate primarily from the locus coeruleus, rather than ventral tegmental area”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Kempadoo et al., 2016
Hippocampal opto-stimulation of DA axon terminals from the locus coeruleus during learning facilitated long-term OPP memory.
“hippocampal opto-stimulation of the DA axon terminals from the locus coeruleus during learning facilitated long-term OPP memory”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Kempadoo et al., 2016
This facilitation effect was blocked by pre-sample trial infusions of SCH23390 but not the β-adrenergic-R antagonist propranolol into the dorsal hippocampus.
“This facilitation effect was blocked by pre-sample trial infusions of SCH23390, but not of the β-adrenergic-R antagonist propranolol, into the dorsal hippocampus”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Kempadoo et al., 2016
DA release in the hippocampus promotes spatial memory, reward-associated memory, novel-object recognition and memory consolidation.
“DA release in the hippocampus promotes spatial memory, rewardassociated memory, novel-object recognition and memory consolida tion (Broussard et al., 2016; Kempadoo et al., 2016; Mamad et al., 2017; McNamara et al., 2014; Rosen et al., 2015; Rossato et al., 2009; Takeuchi et al., 2016).”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Kempadoo et al., 2016
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- Authors
- Kempadoo, K. A., Mosharov, E. V., Choi, S. J., Sulzer, D., & Kandel, E. R.
- Affiliations
- Columbia University (US)
- New York State Psychiatric Institute (US)
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-12-07
- Volume
- 113
- Issue
- 51
- Pages
- 14835-14840
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5187750
- OpenAlex
- W2560490590
- Cited by
- 647
- References
- 38
- Citations by year
- 2026: 57 · 2025: 79 · 2024: 95 · 2023: 76 · 2022: 67 · 2021: 70 · 2020: 62 · 2019: 59 · 2018: 61 · 2017: 19 · 2014: 1
- FWCI
- 29.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Burroughs Wellcome Fund (n/a)
- HHS | National Institutes of Health (T32 MH015174-37, R01 DA07418, R01 DA010154)
- HHS | NIH | National Institute of Neurological Disorders and Stroke (R01 NS07522)
- Parkinson's Disease Foundation (n/a)
- Howard Hughes Medical Institute (n/a)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- dopamine release, locus coeruleus, dorsal hippocampus, spatial learning and memory, noradrenergic neurons, ventral tegmental area, dopamine D1/D5 receptors, selective attention, optogenetic stimulation, dopamine signaling
- MeSH terms
- Animals, Axons, Behavior, Animal, Dopamine, Hippocampus, Locus Coeruleus, Male, Memory, Mice, Inbred C57BL, Synaptic Transmission, Neurons, Mice, Optogenetics, Spatial Learning
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