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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The IPN receives massive cholinergic innervation from the MHb, with MHb cholinergic neurons coreleasing glutamate and providing the major source of glutamatergic input to the IPN.
“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
Medial habenula axon terminals to the interpeduncular nucleus contain both vGluT1/2 and VAChT and cotransmit glutamate and Ach onto individual IPN neurons.
“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]
Many cholinergic neurons also contain vGluT1/2/3 coexpressed with Ach synthesis, packaging, and release machinery in the striatum, basal forebrain, and medial habenula.
“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]
Immunogold EM and immunoprecipitation suggest that vGluT and VAChT co-package glutamate and ACh into the same synaptic vesicle in mHb-IPN and striatal cholinergic-to-SPN synapses.
“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]
At mHb-IPN synapses, AMPA and NMDA receptors are activated by single action potentials, but nicotinic Ach receptors are activated only slowly after prolonged 50 Hz 5 s stimulation, indicating different transmission modes for glutamate and Ach.
“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]
Ach/glutamate release from the mHb to the IPN has frequency-dependent effects on postsynaptic cells.
“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]
Ach and glutamate are copackaged into the same synaptic vesicles at the mHb-to-IPN synapse.
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Millisecond-timescale, genetically targeted optical control of neural activity
Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G., & Deisseroth, K. A. (2005) · Nature Neuroscience · doi:10.1038/nn1525 · Cited by 4,831 · see citing works
Channelrhodopsin-2, a directly light-gated cation-selective membrane channel
Nagel, G., Szellas, T., Huhn, W., Kateriya, S., Adeishvili, N., Berthold, P. R., Ollig, D., Hegemann, P., & Bamberg, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1936192100 · Cited by 2,672 · see citing works
Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (Ch1–Ch6)
Mesulam, M. M., Mufson, E. J., Wainer, B. H., & Levey, A. I. (1983) · Neuroscience · doi:10.1016/0306-4522(83)90108-2 · Cited by 2,329 · see citing works
CENTRAL CHOLINERGIC SYSTEMS AND COGNITION
Everitt, B. J., & Robbins, T. W. (1997) · Annual Review of Psychology · doi:10.1146/annurev.psych.48.1.649 · Cited by 1,348 · see citing works
The Expression of Vesicular Glutamate Transporters Defines Two Classes of Excitatory Synapse
Fremeau, R. T., Troyer, M. D., Pahner, I., Nygaard, G. O., Tran, C. H., Reimer, R. J., Bellocchio, E. E., Fortin, D. L., Storm‐Mathisen, J., & Edwards, R. H. (2001) · Neuron · doi:10.1016/s0896-6273(01)00344-0 · Cited by 1,266 · see citing works
Nicotinic Acetylcholine Receptors and Nicotinic Cholinergic Mechanisms of the Central Nervous System
Dani, J. A., & Bertrand, D. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105214 · Cited by 1,197 · see citing works
The central cholinergic system studied by choline acetyltransferase immunohistochemistry in the cat
Kimura, H., McGeer, P. L., Peng, J. H., & McGeer, E. G. (1981) · The Journal of Comparative Neurology · doi:10.1002/cne.902000202 · Cited by 966 · see citing works
The habenula: from stress evasion to value-based decision-making
Hikosaka, O. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2866 · Cited by 955 · see citing works
Uptake of Glutamate into Synaptic Vesicles by an Inorganic Phosphate Transporter
Bellocchio, E. E., Reimer, R. J., Fremeau, R. T., & Edwards, R. H. (2000) · Science · doi:10.1126/science.289.5481.957 · Cited by 795 · see citing works
Prefrontal Acetylcholine Release Controls Cue Detection on Multiple Timescales
Parikh, V., Kozak, R., Martinez, V., & Sarter, M. (2007) · Neuron · doi:10.1016/j.neuron.2007.08.025 · Cited by 623 · see citing works
Sutherland, R. J. (1982) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(82)90003-3 · Cited by 537 · see citing works
Dopaminergic terminals in the nucleus accumbens but not the dorsal striatum corelease glutamate
Stuber, G. D., Hnasko, T. S., Britt, J. P., Edwards, R. H., & Bonci, A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1754-10.2010 · Cited by 529 · see citing works
Nicotine addiction and nicotinic receptors: lessons from genetically modified mice
Changeux, J.-P. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2849 · Cited by 453 · cited 1× · see citing works
“Behaviorally, it is suggested to be involved in sleep, stress, pain, and nicotine addiction (Changeux, 2010; Haun et al., 1992; Hikosaka, 2010; Plenge et al., 2002; Salas et al., 2009; Sandyk, 1991).”
BackgroundVesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo
Hnasko, T. S., Chuhma, N., Zhang, H., Goh, G. Y., Sulzer, D., Palmiter, R. D., Rayport, S., & Edwards, R. H. (2010) · Neuron · doi:10.1016/j.neuron.2010.02.012 · Cited by 405 · see citing works
Swanson, L. W., Simmons, D. M., Whiting, P. J., & Lindström, J. (1987) · Journal of Neuroscience · doi:10.1523/jneurosci.07-10-03334.1987 · Cited by 342 · see citing works
Phasic acetylcholine release and the volume transmission hypothesis: time to move on
Sarter, M. F., Parikh, V., & Howe, W. M. (2009) · Nature reviews. Neuroscience · doi:10.1038/nrn2635 · Cited by 340 · see citing works
Glutamatergic signaling by mesolimbic dopamine neurons in the nucleus accumbens
Tecuapetla, F., Patel, J. C., Xenias, H., English, D., Tadros, I., Shah, F., Berlin, J., Deisseroth, K., Rice, M. E., Tepper, J. M., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0265-10.2010 · Cited by 310 · see citing works
Salas, R., Sturm, R., Boulter, J., & De Biasi, M. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4934-08.2009 · Cited by 310 · see citing works
Lecourtier, L., & Kelly, P. H. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.01.004 · Cited by 283 · see citing works
Evidence for "preterminal" nicotinic receptors on GABAergic axons in the rat interpeduncular nucleus
Léna, C., Changeux, J., & Mulle, C. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-06-02680.1993 · Cited by 255 · see citing works
Fast synaptic subcortical control of hippocampal circuits
Varga, V., Losonczy, A., Zemelman, B. V., Borhegyi, Z., Nyiri, G., Domonkos, A., Hangya, B., Holderith, N., Magee, J. C., & Freund, T. F. (2009) · Science · doi:10.1126/science.1178307 · Cited by 248 · see citing works
Mammalian motor neurons corelease glutamate and acetylcholine at central synapses
Nishimaru, H., Restrepo, C. E., Ryge, J., Yanagawa, Y., & Kiehn, O. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501331102 · Cited by 237 · see citing works
Mulle, C., Vidal, C., Benoit, P., & Changeux, J. (1991) · Journal of Neuroscience · doi:10.1523/jneurosci.11-08-02588.1991 · Cited by 200 · see citing works
Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord
Mentis, G. Z., Álvarez, F. J., Bonnot, A., Richards, D. S., González‐Forero, D., Zerda, R., & O'Donovan, M. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502788102 · Cited by 163 · see citing works
Contestabile, A., Villani, L., Fasolo, A., Franzoni, M. F., Gribaudo, L., Øktedalen, O., & Fonnum, F. (1987) · Neuroscience · doi:10.1016/0306-4522(87)90337-x · Cited by 136 · see citing works
Wang, Z., Young, L. J., Liu, Y., & Insel, T. R. (1997) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19970224)378:4 · Cited by 135 · see citing works
Neurochemical phenotypes of the afferent and efferent projections of the mouse medial habenula
Qin, C., & Luo, M. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.03.085 · Cited by 133 · see citing works
Self-citationFacilitation of glutamatergic neurotransmission by presynaptic nicotinic acetylcholine receptors
Girod, R., Barazangi, N., McGehee, D., & Role, L. W. (2000) · Neuropharmacology · doi:10.1016/s0028-3908(00)00145-3 · Cited by 122 · see citing works
Brn3a and Nurr1 Mediate a Gene Regulatory Pathway for Habenula Development
Quina, L. A., Wang, S., Ng, L., & Turner, E. E. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.2430-09.2009 · Cited by 110 · see citing works
Haun, F., Eckenrode, T. C., & Murray, M. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-08-03282.1992 · Cited by 91 · see citing works
Glutamate and acetylcholine corelease at developing synapses
Li, W., Soffe, S. R., & Roberts, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404864101 · Cited by 86 · see citing works
Chemical transmission in the rat interpeduncular nucleus in vitro.
Brown, D. A., Docherty, R. J., & Halliwell, J. V. (1983) · The Journal of Physiology · doi:10.1113/jphysiol.1983.sp014831 · Cited by 84 · see citing works
Allen, T. G. J., Abogadie, F. C., & Brown, D. A. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3979-05.2006 · Cited by 79 · see citing works
Dougherty, K. D., & Milner, T. A. (1999) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19990428)407:1 · Cited by 76 · see citing works
Relevance of the Habenular Complex to Neuropsychiatry: A Review and Hypothesis
Sandyk, R. (1991) · International Journal of Neuroscience · doi:10.3109/00207459108990738 · Cited by 70 · see citing works
Girod, R., & Role, L. W. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-14-05182.2001 · Cited by 62 · see citing works
Acetylcholine release in interpeduncular nucleus following the stimulation of habenula
Sastry, B. R., Zialkowski, S. E., Hansen, L. M., Kavanagh, J. P., & Evoy, E. M. (1979) · Brain Research · doi:10.1016/0006-8993(79)90032-5 · Cited by 38 · see citing works
Characterization of Epibatidine Binding to Medial Habenula: Potential Role in Analgesia
Plenge, P., Mellerup, E. T., & Wörtwein, G. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.033498 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Optogenetics in neural systems
Yizhar, O., Fenno, L. E., Davidson, T. J., Mogri, M., & Deisseroth, K. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.004 · Cited by 1,881 · see citing works
Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior
Picciotto, M. R., Higley, M. J., & Mineur, Y. S. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.036 · Cited by 1,404 · see citing works
A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing
Madisen, L., Mao, T., Koch, H., Zhuo, J.-M., Berenyi, A., Fujisawa, S., Hsu, Y.-W. A., Garcia, A. J., Gu, X., Zanella, S., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3078 · Cited by 1,398 · see citing works
Mattis, J., Tye, K. M., Ferenczi, E. A., Ramakrishnan, C., O'Shea, D. J., Prakash, R., Gunaydin, L. A., Hyun, M., Fenno, L. E., Gradinaru, V., et al. (2012) · Nature Methods · doi:10.1038/nmeth.1808 · Cited by 780 · see citing works
Zhao, S., Ting, J. T., Atallah, H. E., Qiu, L., Tan, J., Gloss, B., Augustine, G. J., Deisseroth, K., Luo, M., Graybiel, A. M., et al. (2011) · Nature Methods · doi:10.1038/nmeth.1668 · Cited by 653 · see citing works
Self-citationTing, J. T., Daigle, T. L., Chen, Q., & Feng, G. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1096-0_14 · Cited by 631 · see citing works
Self-citationAnatomically defined and functionally distinct dorsal raphe serotonin sub-systems
Ren, J., Friedmann, D., Xiong, J., Liu, C. D., Ferguson, B. R., Weerakkody, T., DeLoach, K. E., Ran, C., Pun, A., Sun, Y., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.043 · Cited by 498 · see citing works
Self-citationDorsal raphe neurons signal reward through 5-HT and glutamate
Liu, Z., Zhou, J., Li, Y., Hu, F., Lu, Y., Ma, M., Feng, Q., Zhang, J.-E., Wang, D., Zeng, J., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.010 · Cited by 469 · see citing works
Self-citationCholinergic modulation of the hippocampal region and memory function
Haam, J., & Yakel, J. L. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14052 · Cited by 446 · see citing works
Zhan, C., Zhou, J., Feng, Q., Zhang, J.-E., Lin, S., Bao, J., Wu, P., & Luo, M. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2742-12.2013 · Cited by 444 · see citing works
Self-citationA thalamic input to the nucleus accumbens mediates opiate dependence
Zhu, Y., Wienecke, C. F. R., Nachtrab, G. T., & Chen, X. (2016) · Nature · doi:10.1038/nature16954 · Cited by 386 · see citing works
A genetically encoded fluorescent acetylcholine indicator for in vitro and in vivo studies
Jing, M., Zhang, P., Wang, G., Feng, J., Mesik, L., Zeng, J., Jiang, H., Wang, S., Looby, J. C., Guagliardo, N. A., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4184 · Cited by 378 · see citing works
Self-citationFrom glutamate co-release to vesicular synergy: vesicular glutamate transporters
El Mestikawy, S., Wallén-Mackenzie, Å., Fortin, G. M., Descarries, L., & Trudeau, L.-E. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn2969 · Cited by 385 · see citing works
A cellular and regulatory map of the cholinergic nervous system of C. elegans
Pereira, L., Kratsios, P., Serrano-Saiz, E., Sheftel, H., Mayo, A. E., Hall, D. H., White, J. G., LeBoeuf, B., Garcia, L. R., Alon, U., et al. (2015) · eLife · doi:10.7554/elife.12432 · Cited by 365 · see citing works
Molecular characterization of the subnuclei in rat habenula
Aizawa, H., Kobayashi, M. S., Tanaka, S., Fukai, T., & Okamoto, H. (2012) · The Journal of Comparative Neurology · doi:10.1002/cne.23167 · Cited by 288 · see citing works
Neurotransmitter Corelease: Mechanism and Physiological Role
Hnasko, T. S., & Edwards, R. H. (2012) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020911-153315 · Cited by 284 · see citing works
Diversity of native nicotinic receptor subtypes in mammalian brain
Zoli, M., Pistillo, F., & Gotti, C. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.11.003 · Cited by 277 · see citing works
Cerebellar nuclei evolved by repeatedly duplicating a conserved cell-type set
Kebschull, J. M., Richman, E. B., Ringach, N., Friedmann, D., Albarran, E., Kolluru, S. S., Jones, R. C., Allen, W. E., Wang, Y., Cho, S. W., et al. (2020) · Science · doi:10.1126/science.abd5059 · Cited by 253 · see citing works
Hypothalamic Circuits for Predation and Evasion
Li, Y., Zeng, J., Zhang, J.-E., Yue, C., Zhong, W., Liu, Z., Feng, Q., & Luo, M. (2018) · Neuron · doi:10.1016/j.neuron.2018.01.005 · Cited by 212 · see citing works
Self-citationNeural Systems Governed by Nicotinic Acetylcholine Receptors: Emerging Hypotheses
Miwa, J. M., Freedman, R., & Lester, H. A. (2011) · Neuron · doi:10.1016/j.neuron.2011.03.014 · Cited by 205 · see citing works
GLP-1 acts on habenular avoidance circuits to control nicotine intake
Tuesta, L. M., Chen, Z., Duncan, A., Fowler, C. D., Ishikawa, M., Lee, B. R., Liu, X.-A., Lu, Q., Cameron, M., Hayes, M. R., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4540 · Cited by 200 · see citing works
Corelease of acetylcholine and GABA from cholinergic forebrain neurons
Saunders, A., Granger, A. J., & Sabatini, B. L. (2015) · eLife · doi:10.7554/elife.06412 · Cited by 200 · see citing works
Nicotinic acetylcholine receptors and nicotine addiction: A brief introduction
Wittenberg, R. E., Wolfman, S. L., Biasi, M. D., & Dani, J. A. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108256 · Cited by 200 · see citing works
Jiang, L., Kundu, S., Lederman, J., López‐Hernández, G. Y., Ballinger, E. C., Wang, S., Talmage, D. A., & Role, L. W. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.028 · Cited by 186 · see citing works
Schöne, C., Apergis‐Schoute, J., Sakurai, T., Adamantidis, A., & Burdakov, D. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.055 · Cited by 190 · see citing works
Molecular Mechanisms Underlying Behaviors Related to Nicotine AddictionPreprint
Picciotto, M. R., & Kenny, P. J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a012112 · Cited by 178 · see citing works
Efferent Pathways of the Mouse Lateral Habenula
Quina, L. A., Tempest, L., Ng, L., Harris, J. A., Ferguson, S. M., Jhou, T. C., & Turner, E. E. (2014) · The Journal of Comparative Neurology · doi:10.1002/cne.23662 · Cited by 165 · see citing works
Extrinsic Sources of Cholinergic Innervation of the Striatal Complex: A Whole-Brain Mapping Analysis
Dautan, D., Bay, H. H., Bolam, J. P., Gerdjikov, T. V., & Mena‐Segovia, J. (2016) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2016.00001 · Cited by 172 · see citing works
Vesicular and Plasma Membrane Transporters for Neurotransmitters
Blakely, R. D., & Edwards, R. H. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005595 · Cited by 169 · see citing works
Transcriptional and spatial resolution of cell types in the mammalian habenula
Hashikawa, Y., Hashikawa, K., Rossi, M. A., Basiri, M. L., Liu, Y., Johnston, N. L., Ahmad, O. R., & Stuber, G. D. (2020) · Neuron · doi:10.1016/j.neuron.2020.03.011 · Cited by 167 · see citing works
Zhao-Shea, R., DeGroot, S. R., Liu, L., Vallaster, M., Pang, X.-Y., Su, Q., Gao, G., Rando, O. J., Martin, G. E., George, O., et al. (2015) · Nature Communications · doi:10.1038/ncomms7770 · Cited by 166 · see citing works
Zhang, J.-E., Tan, L., Ren, Y., Liang, J., Lin, R., Feng, Q., Zhou, J., Hu, F., Ren, J., Wei, C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.06.026 · Cited by 162 · see citing works
Self-citationOptogenetic Control of Cells and Circuits
Miesenböck, G. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100109-104051 · Cited by 158 · see citing works
Mechanisms of Nicotine Addiction
Picciotto, M. R., & Kenny, P. J. (2021) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a039610 · Cited by 157 · see citing works
The habenulo-interpeduncular pathway in nicotine aversion and withdrawal
Antolin-Fontes, B., Ables, J. L., Görlich, A., & Ibañez-Tallon, I. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.11.019 · Cited by 154 · see citing works
Basal forebrain cholinergic signalling: development, connectivity and roles in cognition
Ananth, M. R., Rajebhosale, P., Kim, R., Talmage, D. A., & Role, L. W. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00677-x · Cited by 148 · see citing works
The fate of the brain cholinergic neurons in neurodegenerative diseases
Pepeu, G., & Giovannini, M. G. (2017) · Brain Research · doi:10.1016/j.brainres.2017.06.023 · Cited by 144 · see citing works
Mancarci, B. O., Toker, L., Tripathy, S. J., Li, B., Rocco, B. R., Sibille, E. L., & Pavlidis, P. (2017) · eNeuro · doi:10.1523/eneuro.0212-17.2017 · Cited by 138 · see citing works
Lebois, E. P., Thorn, C. A., Edgerton, J. R., Popiolek, M., & Xi, S. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.11.018 · Cited by 141 · see citing works
Cholinergic circuits in cognitive flexibility
Prado, V. F., Janíčková, H., Al‐Onaizi, M., & Prado, M. A. M. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.09.013 · Cited by 143 · see citing works
Cholinergic modulation of spatial learning, memory and navigation
Solari, N., & Hangya, B. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14089 · Cited by 139 · see citing works
The medial habenula: still neglected
Viswanath, H., Carter, A. Q., Baldwin, P. R., Molfese, D. L., & Salas, R. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00931 · Cited by 133 · see citing works
Shih, P.-Y., Engle, S. E., Oh, G., Deshpande, P., Puskar, N. L., Lester, H. A., & Drenan, R. M. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0476-14.2014 · Cited by 136 · see citing works
Regulation of cholinergic activity by the vesicular acetylcholine transporter
Prado, V. F., Roy, A., Kolisnyk, B., Gros, R., & Prado, M. A. M. (2013) · Biochemical Journal · doi:10.1042/bj20121662 · Cited by 133 · see citing works
Ma, M., & Luo, M. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0058-12.2012 · Cited by 130 · see citing works
Self-citationBasal Forebrain Cholinergic Modulation of Sleep Transitions
Irmak, S. O., & de Lecea, L. (2014) · SLEEP · doi:10.5665/sleep.4246 · Cited by 132 · see citing works
Distribution of vesicular glutamate transporters in the human brain
Vigneault, É., Poirel, O., Riad, M., Prud’homme, J., Dumas, S., Turecki, G., Fasano, C., Mechawar, N., & Mestikawy, S. E. (2015) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2015.00023 · Cited by 132 · see citing works
Zhao-Shea, R., Liu, L., Pang, X., Gardner, P. D., & Tapper, A. R. (2013) · Current Biology · doi:10.1016/j.cub.2013.09.041 · Cited by 129 · see citing works
Habenular CB1 Receptors Control the Expression of Aversive Memories
Gómez, E. S., Busquets-García, A., Hu, F., Mehidi, A., Cannich, A., Roux, L., Louit, I., Alonso, L., Wiesner, T., Georges, F. E., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.08.035 · Cited by 127 · see citing works
Self-citationSynaptic Vesicle Recycling Pathway Determines Neurotransmitter Content and Release Properties
Silm, K., Yang, J., Marcott, P. F., Asensio, C. S., Eriksen, J., Guthrie, D. A., Newman, A. H., Ford, C., & Edwards, R. H. (2019) · Neuron · doi:10.1016/j.neuron.2019.03.031 · Cited by 131 · see citing works
Aroniadou‐Anderjaska, V., Apland, J. P., Figueiredo, T. H., Furtado, M. D. A., & Braga, M. F. M. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108298 · Cited by 126 · see citing works
Kolisnyk, B., Guzmán-Lenis, M.-S., Raulic, S., Fan, J., Magalhães, A. C., Feng, G., Gros, R., Prado, V. F., & Prado, M. A. M. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0395-13.2013 · Cited by 125 · see citing works
Self-citationTrueta, C., & De‐Miguel, F. F. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00319 · Cited by 122 · see citing works
Neurobiological Mechanisms of Nicotine Reward and Aversion
Wills, L. P., Ables, J. L., Braunscheidel, K. M., Caligiuri, S. P. B., Elayouby, K. S., Fillinger, C., Ishikawa, M., Moen, J. K., & Kenny, P. J. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.121.000299 · Cited by 126 · see citing works
A cholinergic basal forebrain feeding circuit modulates appetite suppression
Herman, A. M., Ortiz‐Guzman, J., Kochukov, M. Y., Herman, I., Quast, K. B., Patel, J. M., Tepe, B., Carlson, J. C., Ung, K., Selever, J., et al. (2016) · Nature · doi:10.1038/nature19789 · Cited by 121 · see citing works
Xiao, C., Zhou, C., Jiang, J., & Cui, Y. (2019) · Acta Pharmacologica Sinica · doi:10.1038/s41401-019-0299-4 · Cited by 120 · see citing works
Habenular TCF7L2 links nicotine addiction to diabetes
Duncan, A., Heyer, M. P., Ishikawa, M., Caligiuri, S. P. B., Liu, X.-A., Chen, Z., Micioni Di Bonaventura, M. V., Elayouby, K. S., Ables, J. L., Howe, W. M., et al. (2019) · Nature · doi:10.1038/s41586-019-1653-x · Cited by 119 · see citing works
Hsu, Y. A., Wang, S. D., Wang, S., Morton, G., Zariwala, H. A., de la Iglesia, H. O., & Turner, E. E. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1861-14.2014 · Cited by 115 · see citing works
Pistillo, F., Clementi, F., Zoli, M., & Gotti, C. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2014.10.002 · Cited by 113 · see citing works
Anatomical and single-cell transcriptional profiling of the murine habenular complex
Wallace, M. L., Huang, K. W., Hochbaum, D., Hyun, M., Radeljic, G., & Sabatini, B. L. (2020) · eLife · doi:10.7554/elife.51271 · Cited by 113 · see citing works
Dual-transmitter systems regulating arousal, attention, learning and memory
Ma, S., Hangya, B., Leonard, C. S., Wisden, W., & Gundlach, A. L. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.07.009 · Cited by 103 · see citing works
Görlich, A., Antolin‐Fontes, B., Ables, J. L., Frahm, S., Ślimak, M. A., Dougherty, J. D., & Ibáñez-Tallon, I. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1313103110 · Cited by 109 · see citing works
Butyrylcholinesterase and the cholinergic system
Reid, G. A., Chilukuri, N., & Darvesh, S. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.12.054 · Cited by 105 · see citing works
Cholinergic modulation of synaptic integration and dendritic excitability in the striatum
Oldenburg, I. A., & Ding, J. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.04.004 · Cited by 103 · see citing works
Herman, A. M., Huang, L., Murphey, D. K., Garcia, I., & Arenkiel, B. R. (2014) · eLife · doi:10.7554/elife.01481 · Cited by 99 · see citing works
Gardon, O., Faget, L. C., Chung, P. C. S., Matifas, A., Massotte, D., & Kieffer, B. L. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.07.053 · Cited by 101 · see citing works
Anxiety and Nicotine Dependence: Emerging Role of the Habenulo-Interpeduncular Axis
Molas, S., DeGroot, S. R., Zhao-Shea, R., & Tapper, A. R. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.11.001 · Cited by 100 · see citing works
Piet, R., Kalil, B., McLennan, T., Porteous, R. W., Czieselsky, K., & Herbison, A. E. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0658-18.2018 · Cited by 100 · see citing works
Striatal cholinergic neurotransmission requires VGLUT3
Nelson, A. B., Bussert, T. G., Kreitzer, A. C., & Seal, R. P. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0901-14.2014 · Cited by 99 · see citing works
An essential role of acetylcholine-glutamate synergy at habenular synapses in nicotine dependence
Frahm, S., Antolin-Fontes, B., Görlich, A., Zander, J.-F., Ahnert-Hilger, G., & Ibañez-Tallon, I. (2015) · eLife · doi:10.7554/elife.11396 · Cited by 98 · see citing works
Multiplexed neurochemical signaling by neurons of the ventral tegmental area
Barker, D. J., Root, D. H., Zhang, S., & Morales, M. (2016) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2015.12.016 · Cited by 99 · see citing works
Abbott, S. B. G., Kanbar, R., Bochorishvili, G., Coates, M. B., Stornetta, R. L., & Guyenet, P. G. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.232157 · Cited by 98 · see citing works
Mouse transgenic approaches in optogenetics
Zeng, H., & Madisen, L. (2012) · Progress in brain research · doi:10.1016/b978-0-444-59426-6.00010-0 · Cited by 96 · see citing works
Hsu, Y. A., Tempest, L., Quina, L. A., Wei, A. D., Zeng, H., & Turner, E. E. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2927-13.2013 · Cited by 95 · see citing works
Guzmán, M. S., Jaeger, X. D., Raulic, S., Souza, I. A., Li, A. X., Schmid, S., Menon, R. S., Gainetdinov, R. R., Caron, M. G., Bartha, R., et al. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001194 · Cited by 94 · see citing works
Quina, L. A., Harris, J. A., Zeng, H., & Turner, E. E. (2017) · The Journal of Comparative Neurology · doi:10.1002/cne.24221 · Cited by 85 · see citing works
Cholinergic left-right asymmetry in the habenulo-interpeduncular pathway
Hong, E., Santhakumar, K., Akitake, C. A., Ahn, S. J., Thisse, C., Thisse, B., Wyart, C., Mangin, J., & Halpern, M. E. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1319566110 · Cited by 82 · see citing works
Nicotinic Receptors in Addiction Pathways
Leslie, F. M., Mojica, C., & Reynaga, D. D. (2012) · Molecular Pharmacology · doi:10.1124/mol.112.083659 · Cited by 87 · see citing works
Controlling the Elements: An Optogenetic Approach to Understanding the Neural Circuits of Fear
Johansen, J. P., Wolff, S. B. E., Lüthi, A., & LeDoux, J. E. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.10.023 · Cited by 84 · see citing works
The Right Dorsal Habenula Limits Attraction to an Odor in Zebrafish
Krishnan, S., Mathuru, A. S., Kibat, C., Rahman, M., Lupton, C., Stewart, J., Claridge‐Chang, A., Yen, S., & Jesuthasan, S. J. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.073 · Cited by 83 · see citing works
Ni, Y., Feng, J., Liu, J., Yu, H., Wei, H., Du, Y., Liu, L., Sun, L., Zhou, J., & Xu, W. (2021) · Advanced Science · doi:10.1002/advs.202102036 · Cited by 83 · see citing works
Mechanisms Generating Dual-Component Nicotinic EPSCs in Cortical Interneurons
Bennett, C., Arroyo, S., Berns, D. S., & Hestrin, S. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3565-12.2012 · Cited by 80 · see citing works
Lima, L. B., Bueno, D., Leite, F., Souza, S., Gonçalves, L., Furigo, I. C., Donato, J., & Metzger, M. (2017) · The Journal of Comparative Neurology · doi:10.1002/cne.24217 · Cited by 80 · see citing works
Sun, Y.-G., Pita‐Almenar, J. D., Wu, C., Renger, J. J., Uebele, V. N., Lu, H., & Beierlein, M. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3177-12.2013 · Cited by 79 · see citing works
Noradrenergic and cholinergic systems take centre stage in neuropsychiatric diseases of ageing
Orlando, I. F., Shine, J. M., Robbins, T. W., Rowe, J. B., & O’Callaghan, C. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105167 · Cited by 77 · see citing works
Serrano‐Saiz, E., Leyva‐Díaz, E., Cruz, E. D. L., & Hobert, O. (2018) · Current Biology · doi:10.1016/j.cub.2018.06.045 · Cited by 72 · see citing works
Metzger, M., Souza, R., Lima, L. B., Bueno, D., Gonçalves, L., Sego, C., Donato, J., & Shammah‐Lagnado, S. J. (2019) · European Journal of Neuroscience · doi:10.1111/ejn.14647 · Cited by 77 · see citing works
Understanding the habenula: A major node in circuits regulating emotion and motivation
Ables, J. L., Park, K., & Ibáñez-Tallon, I. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106734 · Cited by 76 · see citing works
Trudeau, L., & Mestikawy, S. E. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00113 · Cited by 79 · see citing works
Bell, K. A., Shim, H., Chen, C.-K., & McQuiston, A. R. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.08.024 · Cited by 74 · see citing works
A circuit-based mechanism underlying familiarity signaling and the preference for novelty
Molas, S., Zhao-Shea, R., Liu, L., DeGroot, S. R., Gardner, P. D., & Tapper, A. R. (2017) · Nature Neuroscience · doi:10.1038/nn.4607 · Cited by 72 · see citing works
DeGroot, S. R., Zhao-Shea, R., Chung, L., Klenowski, P. M., Sun, F., Molas, S., Gardner, P. D., Li, Y., & Tapper, A. R. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.06.018 · Cited by 71 · see citing works
From controlled to compulsive drug-taking: The role of the habenula in addiction
Mathis, V., & Kenny, P. J. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.06.018 · Cited by 71 · see citing works
Upmanyu, N., Jin, J., Emde, H. V. D., Ganzella, M., Bösche, L., Malviya, V. N., Zhuleku, E., Politi, A. Z., Ninov, M., Silbern, I., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.02.008 · Cited by 69 · see citing works
Luchicchi, A., Bloem, B., Viaña, J. N. M., Mansvelder, H. D., & Role, L. W. (2014) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2014.00024 · Cited by 70 · see citing works
Martyn, A. C., Jaeger, X. D., Magalhães, A. C., Kesarwani, R., Gonçalves, D. F., Raulic, S., Guzmán, M. S., Jackson, M. F., Izquierdo, I., MacDonald, J. F., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215381109 · Cited by 69 · see citing works
Sugita, S., Fleming, L. L., Wood, C., Doss, S. V., Gomes, M. P. S. M., de Camargo, W. L., Naves, L. A., Prado, V. F., Prado, M. A. M., Guatimosim, C., et al. (2016) · Skeletal Muscle · doi:10.1186/s13395-016-0105-7 · Cited by 69 · see citing works
The Role of the Medial Habenula Cholinergic System in Addiction and Emotion-Associated Behaviors
Lee, H. W., Yang, S. H., Kim, J. Y., & Kim, H. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00100 · Cited by 69 · see citing works
Modulation of dopamine release in the striatum by physiologically relevant levels of nicotine
Wang, L., Shang, S., Kang, X., Teng, S., Zhu, F., Liu, B., Wu, Q., Li, M., Liu, W. Y., Xu, H., et al. (2014) · Nature Communications · doi:10.1038/ncomms4925 · Cited by 68 · see citing works
Target selectivity of septal cholinergic neurons in the medial and lateral entorhinal cortex
Desikan, S., Koser, D. E., Neitz, A., & Monyer, H. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1716531115 · Cited by 69 · see citing works
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
