The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Habenula “Cholinergic” Neurons Corelease Glutamate and Acetylcholine and Activate Postsynaptic Neurons via Distinct Transmission Modes
Open accessAbstract
Acetylcholine is an important neurotransmitter, and the habenulo-interpeduncular projection is a major cholinergic pathway in the brain. To study the physiological properties of cholinergic transmission in the interpeduncular nucleus (IPN), we used a transgenic mouse line in which the light-gated cation channel ChannelRhodopsin-2 is selectively expressed in cholinergic neurons. Cholinergic axonal terminals were activated by light pulses, and postsynaptic responses were recorded from IPN neurons. Surprisingly, brief photostimulation produces fast excitatory postsynaptic currents that are mediated by ionotropic glutamate receptors, suggesting wired transmission of glutamate. By contrast, tetanic photostimulation generates slow inward currents that are largely mediated by nicotinic acetylcholine receptors, suggesting volume transmission of acetylcholine. Finally, vesicular transporters for glutamate and acetylcholine are coexpressed on the same axonal terminals in the IPN. These results strongly suggest that adult brain "cholinergic" neurons can corelease glutamate and acetylcholine, but these two neurotransmitters activate postsynaptic neurons via different transmission modes.
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In the citing paper
“The IPN receives massive cholinergic innervation from MHb (Ren et al. 2011), with MHb cholinergic neurons coreleasing glutamate and providing the major source of glutamatergic input to the IPN (Ren et al. 2011).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Ren et al. 2011
Experimental — accuracy not yet measuredIn the citing paper
“Axon terminals from mHb to the interpeduncular nucleus (IPN) contain both vGluT1/2 and VAChT and cotransmit both glutamate and Ach onto individual neurons in the IPN.56”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [56]
In the citing paper
“However, many of these neurons also contain the vesicular glutamate transporters (vGluT1/2/3) that are coexpressed with molecular machinery for Ach synthesis, vesicular packaging, and release in multiple brain regions, including the striatum, basal forebrain, and medial habenula (mHb).22,56,57”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [56]
In the citing paper
“Immunogold EM and immunoprecipitation experiments suggest that vGluT and VAChT co-package glutamate and ACh into the same synaptic vesicle in both mHb to IPN synapses and striatal cholinergic to medium spiny neuron synapses 21,22,56 (Figure 1A).”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [56]
In the citing paper
“Although postsynaptic AMPA and NMDA receptors are activated by single action potentials (APs) in the presynaptic axon, nicotinic Ach receptors (nAchRs) were only activated slowly following prolonged (50 Hz, 5 s) stimulation of inputs, indicating that glutamate and Ach have different transmission modes.56”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [56]
In the citing paper
“Investigations into Ach/glutamate release from the mHb to the IPN revealed frequency-dependent effects of cotransmission on postsynaptic cells.”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [56]
In the citing paper
“Several groups have found evidence for Ach and glutamate being copackaged into the same synaptic vesicles at this synapse 21,22,56,124”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [56]
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Metadata
- Authors
- Ren, J., Qin, C., Hu, F., Tan, J., Qiu, L., Zhao, S., Feng, G., & Luo, M.
- Affiliations
- Beijing Normal University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- National Institute of Biological Sciences, Beijing (CN)
- Duke Medical Center (US)
- McGovern Institute for Brain Research (US)
- Corresponding author
- Luo, Minmin
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 69
- Issue
- 3
- Pages
- 445-452
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2103498534
- Cited by
- 315
- References
- 38
- Citations by year
- 2026: 5 · 2025: 18 · 2024: 14 · 2023: 12 · 2022: 14 · 2021: 18 · 2020: 26 · 2019: 21 · 2018: 19 · 2017: 25 · 2016: 20 · 2015: 19 · 2014: 39 · 2013: 14 · 2012: 26
- FWCI
- 13.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Elsevier eBooks
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- habenula, interpeduncular nucleus, cholinergic neurons, corelease, glutamate, acetylcholine, volume transmission, ionotropic glutamate receptors, nicotinic acetylcholine receptors, channelrhodopsin-2, photostimulation, vesicular transporters
- MeSH terms
- Acetylcholine, Animals, Cholinergic Fibers, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Synaptic Transmission, Neurons, Presynaptic Terminals, Glutamic Acid, Habenula, Mice, Synaptic Potentials
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