Neurotransmitter Corelease: Mechanism and Physiological Role
Open accessAbstract
Neurotransmitter identity is a defining feature of all neurons because it constrains the type of information they convey, but many neurons release multiple transmitters. Although the physiological role for corelease has remained poorly understood, the vesicular uptake of one transmitter can regulate filling with the other by influencing expression of the H + electrochemical driving force. In addition, the sorting of vesicular neurotransmitter transporters and other synaptic vesicle proteins into different vesicle pools suggests the potential for distinct modes of release. Corelease thus serves multiple roles in synaptic transmission.
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Many neurotransmitter co-release patterns had been documented previously.
“Although many of these neurotransmitter co-release patterns had been documented previously55–57”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [56]
The resulting pH gradient and vesicle membrane potential can power neurotransmitter uptake by vesicular transporters.
“This creates a pH gradient (DpH) and a vesicular membrane potential (DJ), both of which can power the uptake of neurotransmitters by vesicular transporters (Table 1).16”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [16]
In multitransmitter neurons, differential sensitivity of vesicular transporters to intravesicular pH or membrane potential is important for co-packaging.
“In multitransmitter neurons, where vesicular packaging of more than one neurotransmitter occurs, it is important to consider how vesicular transporters are differentially sensitive to intravesicular factors such as pH or membrane potential.16”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [16]
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Higley, M. J., Gittis, A. H., Oldenburg, I. A., Balthasar, N., Seal, R. P., Edwards, R. H., Lowell, B. B., Kreitzer, A. C., & Sabatini, B. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019155 · Cited by 175 · cited 1× · see citing works
“Consistent with VGLUT3 expression by these cells, the response was abolished in VGLUT3 KO mice (110).”
Cellular Mechanisms for Direction Selectivity in the Retina
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“Indeed, GABA release, presumably from SACs, appears to be essential for direction selectivity (79).”
Bo, G. D., St-Gelais, F., Danik, M., Williams, S., Cotton, M., & Trudeau, L. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02277.x · Cited by 159 · cited 1× · see citing works
“However, the postnatal decline in VGLUT2 expression by midbrain dopamine neurons (60, 63) raised the possibility that VGLUT2 expression in vitro (67) might simply reflect dedifferentiation.”
A chloride conductance in VGLUT1 underlies maximal glutamate loading into synaptic vesicles
Schenck, S., Wojcik, S. M., Brose, N., & Takamori, S. (2009) · Nature Neuroscience · doi:10.1038/nn.2248 · Cited by 155 · see citing works
Synaptic and Vesicular Coexistence of VGLUT and VGAT in Selected Excitatory and Inhibitory Synapses
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“Although Cl− suffices to promote pH and to stimulate the pH-dependent storage of cationic transmitters (29, 49), we and others found that glutamate can also increase the packaging of monoamines (29, 50, 51) and ACh (52) into isolated synaptic vesicles.”
The ability of the mesocortical dopamine system to operate in distinct temporal modes
Lapish, C. C., Kroener, S., Durstewitz, D., Lavı́n, A., & Seamans, J. K. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0527-8 · Cited by 153 · see citing works
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“Taken together, however, the data suggest that synaptic vesicles storing glutamate, which are the most abundant in brain, express more VGLUT than ClC; Cl− entry would indeed dissipate the ψ required for vesicular glutamate transport, and previous work has suggested that substrates can inhibit the Cl− conductance assoc…”
Staggered development of GABAergic and glycinergic transmission in the MNTB
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Synaptic glutamate release by postnatal rat serotonergic neurons in microculture
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“Stimulation of both serotonin (12) and dopamine (13) neurons produced fast excitatory currents blocked by glutamate receptor antagonists, indicating the potential for glutamate corelease to activate postsynaptic receptors.”
Regulation of Glutamate Transport into Synaptic Vesicles by Chloride and Proton Gradient
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Glutamate in dopamine neurons: Synaptic versus diffuse transmission
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Plasticity of the GABAergic Phenotype of the “Glutamatergic” Granule Cells of the Rat Dentate Gyrus
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“GABA and glycine exchange for an unknown number of H+, and as zwitterions, their uptake depends equally on pH and on ψ (20, 21).”
VGLUT2 in dopamine neurons is required for psychostimulant-induced behavioral activation
Birgner, C., Nordenankar, K., Lundblad, M., Méndez, J. A. T., Smith, C., Grevès, M. L., Galter, D., Olson, L., Fredriksson, A., Trudeau, L., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910986107 · Cited by 119 · cited 2× · see citing works
“However, mature conditional knockout (cKO) mice lacking VGLUT2 selectively in dopamine neurons clearly show a reduction in both dopamine storage and evoked dopamine release (29) that presumably accounts for their reduced response to psychostimulants (29, 64).”
Active transport of gamma-aminobutyric acid and glycine into synaptic vesicles
Kish, P. E., Fischer-Bovenkerk, C., & Ueda, T. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.10.3877 · Cited by 119 · cited 1× · see citing works
“GABA and glycine exchange for an unknown number of H+, and as zwitterions, their uptake depends equally on pH and on ψ (20, 21).”
A Leucine-based Motif Mediates the Endocytosis of Vesicular Monoamine and Acetylcholine Transporters
Tan, P. K., Waites, C. L., Liu, Y., Krantz, D. E., & Edwards, R. H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.28.17351 · Cited by 116 · cited 1× · see citing works
“Indeed, all known transporters contain signals that target them to endocytic vesicles, even in non-neural cells (28), and the expression of μH+ by endosomes should in principle drive their activity.”
Self-citationMéndez, J. A. T., Bourque, M.-J., Bo, G. D., Bourdeau, M. L., Danik, M., Williams, S., Lacaille, J., & Trudeau, L. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1331-08.2008 · Cited by 108 · cited 1× · see citing works
“However, the postnatal decline in VGLUT2 expression by midbrain dopamine neurons (60, 63) raised the possibility that VGLUT2 expression in vitro (67) might simply reflect dedifferentiation.”
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Co-Transmission of Dopamine and GABA in Periglomerular Cells
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“Conversely, many monoamine neurons corelease glutamate when grown in culture (12, 13), and dopaminergic periglomerular cells in the olfactory bulb also corelease GABA (14).”
Cocaine-Conditioned Place Preference by Dopamine-Deficient Mice Is Mediated by Serotonin
Hnasko, T. S., Sotak, B. N., & Palmiter, R. D. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3133-07.2007 · Cited by 99 · cited 1× · see citing works
“However, mice can also learn CPP in the absence of dopamine (102, 103), and the cue-reward pairing involved in CPP occurs continuously over the course of 20 min and may therefore not depend on transient subsecond bursts in dopamine neuron firing.”
Self-citationThe dual dopamine‐glutamate phenotype of growing mesencephalic neurons regresses in mature rat brain
Bérubé‐Carrière, N., Riad, M., Bo, G. D., Lévesque, D., Trudeau, L., & Descarries, L. (2009) · The Journal of Comparative Neurology · doi:10.1002/cne.22194 · Cited by 98 · cited 2× · see citing works
“The segregation of monoamine and glutamate markers to different release sites may indeed contribute to the failure to detect VGLUT expression in tyrosine hydroxylase–positive striatal projections by immunoelectron microscopy (60, 68).”
Gorelova, N., Mulholland, P. J., Chandler, L. J., & Seamans, J. K. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhr107 · Cited by 98 · cited 2× · see citing works
“The next year, the Seamans laboratory (92) showed that VTA stimulation in vivo rapidly leads to glutamate release in the prefrontal cortex (PFC).”
Proton: substrate stoichiometries during active transport of biogenic amines in chromaffin ghosts
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TRPM7 facilitates cholinergic vesicle fusion with the plasma membrane
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“Interestingly, the TRPM7 (transient receptor potential cation channel, subfamily M, member 7) channel localizes to synaptic vesicles and influences quantal size, although it also interacts with proteins involved in fusion and affects the frequency of release (77, 78).”
Neagoe, I., Stauber, T., Fidzinski, P., Bergsdorf, E.-Y., & Jentsch, T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.125971 · Cited by 89 · see citing works
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Characterization of ATP Transport into Chromaffin Granule Ghosts
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“Previous work has also demonstrated the synergistic effect of ATP (also an anion) on serotonin uptake by chromaffin granules (46).”
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Glutamate‐Dopamine Cotransmission and Reward Processing in Addiction
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Presynaptic CLC-3 determines quantal size of inhibitory transmission in the hippocampus
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“Indeed, recent work using ClC-3 KO mice has shown major defects in GABA release, apparently due to the impaired acidification of GABAergic synaptic vesicles (40).”
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Vesicular Monoamine and Glutamate Transporters Select Distinct Synaptic Vesicle Recycling Pathways
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Vesicular Inhibitory Amino Acid Transporter Is a Cl−/γ-Aminobutyrate Co-transporter
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“Previous work had not identified a requirement for Cl−, but the apparent affinity of VGAT for Cl− appears high, suggesting that only low concentrations may be required (22).”
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On Cotransmission & Neurotransmitter Phenotype Plasticity
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“Although Cl− suffices to promote pH and to stimulate the pH-dependent storage of cationic transmitters (29, 49), we and others found that glutamate can also increase the packaging of monoamines (29, 50, 51) and ACh (52) into isolated synaptic vesicles.”
Maqueda, J., Ramı́rez, M., Lamas, M., & Gutiérrez, R. (2003) · Neuroscience Letters · doi:10.1016/j.neulet.2003.08.077 · Cited by 31 · see citing works
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“The segregation of monoamine and glutamate markers to different release sites may indeed contribute to the failure to detect VGLUT expression in tyrosine hydroxylase–positive striatal projections by immunoelectron microscopy (60, 68).”
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A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
Yao, Z., van Velthoven, C. T. J., Kunst, M., Zhang, M., McMillen, D., Lee, C., Jung, W., Goldy, J., Abdelhak, A., Aitken, M., et al. (2023) · Nature · doi:10.1038/s41586-023-06812-z · Cited by 1,194 · see citing works
Dopamine: Functions, Signaling, and Association with Neurological Diseases
Klein, M. O., Battagello, D. S., Cardoso, A. R., Hauser, D. N., Bittencourt, J. C., & Correa, R. G. (2019) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-018-0632-3 · Cited by 1,073 · see citing works
The Meningeal Lymphatic System: A New Player in Neurophysiology
Da Mesquita, S., Fu, Z., & Kipnis, J. (2018) · Neuron · doi:10.1016/j.neuron.2018.09.022 · Cited by 479 · see citing works
Functional consequences of neuropeptide and small-molecule co-transmission
Nusbaum, M. P., Blitz, D. M., & Marder, E. E. (2017) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.56 · Cited by 304 · see citing works
Spatial and temporal scales of dopamine transmission
Liu, C., Goel, P., & Kaeser, P. S. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00455-7 · Cited by 302 · see citing works
Ventral Tegmental Area Glutamate Neurons: Electrophysiological Properties and Projections
Hnasko, T. S., Hjelmstad, G. O., Fields, H. L., & Edwards, R. H. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3128-12.2012 · Cited by 287 · see citing works
“In addition to dopamine neurons that corelease glutamate (Hnasko and Edwards, 2012), we find that the midbrain contains a distinct set of glutamatergic projection neurons that do not coexpress dopaminergic markers (Kawano et al., 2006; Yamaguchi et al., 2007, 2011).”
BackgroundSelf-citationProtons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala
Du, J., Reznikov, L. R., Price, M. P., Zha, X., Lü, Y., Moninger, T. O., Wemmie, J. A., & Welsh, M. J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1407018111 · Cited by 279 · see citing works
“Co-release has a parallel with other neurotransmitters (49): Co-release implies that proton exocytosis need not have a unique regulatory mechanism; acidification would be initiated by the same Ca-dependent exocytotic release mechanisms that regulate glutamate release.”
BackgroundMechanisms and functions of GABA co-release
Tritsch, N. X., Granger, A. J., & Sabatini, B. L. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2015.21 · Cited by 261 · see citing works
Structure and Roles of V-type ATPases
Vasanthakumar, T., & Rubinstein, J. L. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2019.12.007 · Cited by 240 · see citing works
Song, Q., Meng, B., Xu, H., & Mao, Z. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00196-0 · Cited by 232 · see citing works
Dual-transmitter neurons: functional implications of co-release and co-transmission
Vaaga, C. E., Borisovska, M., & Westbrook, G. L. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.04.010 · Cited by 221 · see citing works
“This difficulty arises, in part, because in addition to activating postsynaptic receptors, co-released neurotransmitters can modulate pre- and postsynaptic responses and even modulate the packaging of other neurotransmitters into synaptic vesicles [4].”
BackgroundChloride in Vesicular Trafficking and Function
Stauber, T., & Jentsch, T. J. (2012) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183702 · Cited by 216 · see citing works
Ventral tegmental area glutamate neurons co-release GABA and promote positive reinforcement
Yoo, J. H., Zell, V., Gutierrez-Reed, N. A., Wu, J., Ressler, R. L., Shenasa, M. A., Johnson, A. B., Fife, K. H., Faget, L. C., & Hnasko, T. S. (2016) · Nature Communications · doi:10.1038/ncomms13697 · Cited by 210 · see citing works
Self-citationTritsch, N. X., Oh, W., Gu, C., & Sabatini, B. L. (2014) · eLife · doi:10.7554/elife.01936 · Cited by 197 · 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
“Surprisingly, we observed PSCs mediated by GABAA receptors in addition to nicotinic acetylcholine receptors.”
BackgroundAfferent Inputs to Neurotransmitter-Defined Cell Types in the Ventral Tegmental Area
Faget, L. C., Osakada, F., Duan, J., Ressler, R. L., Johnson, A. B., Proudfoot, J., Yoo, J. H., Callaway, E. M., & Hnasko, T. S. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.057 · Cited by 180 · see citing works
“…glutamate transporter 2 (VGLUT2) (Kawano et al., 2006) and the ability of some dopamine neurons to co-release glutamate (Chuhma et al., 2014; Hnasko et al., 2010; Hnasko and Edwards, 2012; Stuber et al., 2010; Tecuapetla et al., 2010) have led to a surge of interest in VTA glutamate neurons.”
BackgroundSelf-citationWakefulness Is Governed by GABA and Histamine Cotransmission
Yu, X., Ye, Z., Houston, C. M., Zecharia, A. Y., Ma, Y., Zhang, Z., Uygun, D. S., Parker, S., Vyssotski, A. L., Yustos, R., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.06.003 · Cited by 171 · see citing works
“, 1998), but often of functionally antagonist pairings, for example, GABA-glutamate, or GABA-acetylcholine or GABA-dopamine (Hnasko and Edwards, 2012; Vaaga et al., 2014).”
Gjorgjieva, J., Drion, G., & Marder, E. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.12.008 · Cited by 127 · see citing works
Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
Korpi, E. R., den Hollander, B., Farooq, U., Vashchinkina, E., Rajkumar, R., Nutt, D. J., Hyytiä, P., & Dawe, G. S. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010967 · Cited by 148 · see citing works
“nature, significant populations of GABAergic and glutamatergic projection neurons have been observed as well (Nair-Roberts et al., 2008; Stuber et al., 2010; Hnasko and Edwards, 2012).”
BackgroundThe multilingual nature of dopamine neurons
Trudeau, L., Hnasko, T. S., Wallén‐Mackenzie, Å., Morales, M., Rayport, S., & Sulzer, D. L. (2014) · Progress in brain research · doi:10.1016/b978-0-444-63425-2.00006-4 · Cited by 138 · see citing works
“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript mechanism may be general (Amilhon et al., 2010; El Mestikawy et al., 2011; Gras et al., 2008; Hnasko and Edwards, 2012).”
Self-citationCholinergic 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
“…a long time the dogma that one neuron stores and releases only one type of classical neurotransmitter has prevailed, accumulating evidence indicate that a vast number of exceptions exist (for recent reviews see (El Mestikawy et al., 2011; Hnasko and Edwards, 2012; Munster-Wandowski et al., 2016).”
BackgroundNeuropeptide and small transmitter coexistence: Fundamental studies and relevance to mental illness
Hökfelt, T., Barde, S., Xu, Z.-Q. D., Kuteeva, E., Rüegg, J., Le Maitre, E., Risling, M., Kehr, J., Ihnatko, R., Theodorsson, E., et al. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00106 · Cited by 139 · see citing works
Li, F., Wang, J., Ma, C., Zhao, Y., Wang, Y., Hasi, A., & Qi, Z. (2013) · PLANT PHYSIOLOGY · doi:10.1104/pp.113.217208 · Cited by 139 · see citing works
“…of GSH tends to make it neuroactive, because all of its three individual amino acid residues can either function as neurotransmitters or interfere with glutamatergic neurotransmission, with Glu and Gly being excitatory and inhibitory neurotransmitters, respectively (Hnasko and Edwards, 2012).”
BackgroundRegulation 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
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
“Proton-dependent carriers, named vesicular glutamate transporters (VGLUTs) 1–3, are responsible for the vesicular accumulation of glutamate (for review see El Mestikawy et al., 2011; Hnasko and Edwards, 2012).”
BackgroundGeneral Principles of Neuronal Co-transmission: Insights From Multiple Model Systems
Svensson, E., Apergis‐Schoute, J., Burnstock, G., Nusbaum, M. P., Parker, D., & Schiöth, H. B. (2019) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00117 · Cited by 128 · see citing works
Cholinergic modulation of striatal microcircuits
Abudukeyoumu, N., Hernández-Flores, T., Garcia-Munoz, M., & Arbuthnott, G. W. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.13949 · Cited by 128 · see citing works
“Co-release from cholinergic interneurons Although it goes against the Dale’s principle of one neurotransmitter per neuron, the concept of corelease is now more accepted (Hnasko & Edwards, 2012).”
BackgroundSynaptic 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
Self-citationVTA Glutamate Neuron Activity Drives Positive Reinforcement Absent Dopamine Co-release
Zell, V., Steinkellner, T., Hollon, N. G., Warlow, S. M., Souter, E. A., Faget, L. C., Hunker, A. C., Jin, X., Zweifel, L. S., & Hnasko, T. S. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.011 · Cited by 127 · see citing works
“Further complexity is added by the fact that some VTA neurons co-release multiple neurotransmitters (Hnasko and Edwards, 2012; Trudeau et al., 2014).”
Self-citationPrinciples of designing interpretable optogenetic behavior experimentsPreprint
Allen, B. D., Singer, A. C., & Boyden, E. S. (2015) · Learning & Memory · doi:10.1101/lm.038026.114 · Cited by 121 · see citing works
“Other changes—including homeostatic plasticity (Turri-giano et al. 1998; Borodinsky et al. 2004; Thiagarajan et al. 2005; Hnasko and Edwards 2012), changes in synaptic function due to retrograde cannabinoid signaling (Kreitzer and Regehr 2001; Wilson and Nicoll 2001), nitric oxide signaling…”
BackgroundNässel, D. R. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00083 · Cited by 119 · see citing works
“Over the years much progress has been made in understanding the functional consequences of co-transmission in the nervous systems of vertebrates (see Svensson et al., 2001; Hnasko and Edwards, 2012; Vaaga et al., 2014).”
BackgroundWu, C., Shih, M.-F. M., Lee, P.-T., & Chiang, A. (2013) · Current Biology · doi:10.1016/j.cub.2013.09.056 · Cited by 118 · see citing works
Mickelsen, L. E., Kolling, F. W., Chimileski, B. R., Fujita, A., Norris, C., Chen, K., Nelson, C. E., & Jackson, A. C. (2017) · eNeuro · doi:10.1523/eneuro.0013-17.2017 · Cited by 119 · see citing works
Mechanisms of neuromodulatory volume transmission
Özçete, Ö. D., Banerjee, A., & Kaeser, P. S. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02608-3 · Cited by 123 · see citing works
“Finally, neuromodulatory neurons often release multiple transmitters; we refer to previous reviews on the topic of co-transmission [26, 27].”
Drosophila melanogaster as a genetic model system to study neurotransmitter transporters
Martin, C. A., & Krantz, D. E. (2014) · Neurochemistry International · doi:10.1016/j.neuint.2014.03.015 · Cited by 113 · see citing works
“This phenomenon has important ramifications for both the possible co-release of neurotransmitters as well as the regulation of the electrochemical gradients that drive transport activity (Guzman et al., 2011; Hnasko and Edwards, 2011).”
Neurotransmitter Switching in the Developing and Adult Brain
Spitzer, N. C. (2017) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-072116-031204 · Cited by 109 · see citing works
“Transmitter coexpression, cotransmission, and corelease have been reviewed recently and are not discussed here (Hnasko & Edwards 2012, Vaaga et al. 2014, Tritsch et al. 2016).”
BackgroundAstrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders
Satarker, S., Bojja, S. L., Gurram, P. C., Mudgal, J., Arora, D. S., & Nampoothiri, M. (2022) · Cells · doi:10.3390/cells11071139 · Cited by 112 · see citing works
“Interestingly, since glutamate itself is anionic, it acidifies the vesicles and activates the V-ATPases, enhancing the vesicular filling of glutamate via VGLUT [117].”
BackgroundInfluentialDual-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
“This is perhaps not surprising since most, if not all neurons, appear to release one or more classical transmitters and one or more neuropeptides (Hnasko and Edwards, 2012; Vaaga et al., 2014) and this has been reported for the vast majority of neuropeptide systems (see Table 1 for several key…”
Lee, S., Zhang, Y., Chen, M., & Zhou, Z. J. (2016) · Neuron · doi:10.1016/j.neuron.2016.02.023 · Cited by 101 · see citing works
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“Surprisingly, neurons sometimes even contain cotransmitters with supposedly opposing effects, such as excitatory glutamate and inhibitory g-aminobutyric acid (GABA).”
BackgroundInfluentialRecent advancement in nanosensors for neurotransmitters detection: Present and future perspective
Chauhan, N., Soni, S., Agrawal, P., Balhara, Y. P. S., & Jain, U. (2019) · Process Biochemistry · doi:10.1016/j.procbio.2019.12.016 · Cited by 104 · see citing works
SLC18: Vesicular neurotransmitter transporters for monoamines and acetylcholine
Lawal, H. O., & Krantz, D. E. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.07.005 · Cited by 104 · see citing works
“A number of recent studies have demonstrated co-expression of VMAT2 or VAChT with VGLUTs (El Mestikawy et al., 2011; Hnasko and Edwards, 2011).”
BackgroundBodzęta, A., Kahms, M., & Klingauf, J. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.07.040 · Cited by 103 · see citing works
Cotransmission of acetylcholine and GABA
Granger, A. J., Mulder, N., Saunders, A. B., & Sabatini, B. L. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.07.031 · Cited by 98 · see citing works
“…activate genetically-defined cell types has led to a growing appreciation that mammalian neurons can release multiple fast-acting neurotransmitters (Hnasko and Edwards, 2012; Vaaga et al., 2014), subverting the classic notion that neuron classes can be defined by their ability to package and du…”
BackgroundGardon, 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
“…has been intensively studied in recent years, with the notion that glutamate corelease with another neurotransmitter encodes distinct information depending on activation levels (Hnasko and Edwards, 2012), and can convey temporalspecific information (Lapish et al., 2006, Lapish et al., 2007).”
BackgroundAn 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
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
“Identification of the vesicular glutamate transporters (VGLUTs) has greatly enhanced our ability to identify glutamatergic neurons, including many unexpected populations (El Mestikawy et al., 2011; Hnasko and Edwards, 2012).”
BackgroundRole for VGLUT2 in selective vulnerability of midbrain dopamine neurons
Steinkellner, T., Zell, V., Farino, Z. J., Sonders, M. S., Villeneuve, M., Freyberg, R. J., Przedborski, S., Lu, W., Freyberg, Z., & Hnasko, T. S. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95795 · Cited by 102 · see citing works
“(E and F) Rotations were reversed to contraversive by apomorphine [E; 2-way ANOVA followed by Sidak’s multiple comparisons; main effect of treatment: F(1,56) = 4.”
MethodInfluentialSelf-citationMultiplexed 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
“…the brain (Trudeau, 2004; Gillespie et al., 2005; Zhou et al., 2005; Gras et al., 2008; Noh et al., 2010; Higley et al., 2011; Tritsch et al., 2012; Hnasko and Edwards, 2012; Münster-Wandowski et al., 2013; Nelson et al., 2014; Root et al., 2014a; Shabel et al., 2014; Qi et al., 2014; Zhang et…”
BackgroundChen, Z. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00526-9 · Cited by 97 · see citing works
Borden, P. M., Zhang, P., Shivange, A. V., Marvin, J. S., Cichon, J., Dan, C., Podgorski, K., Figueiredo, A. M. P. D., Novák, O., Tanimoto, M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.02.07.939504 · Cited by 94 · see citing works
Neurotransmitter Switching? No Surprise
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Functional Connectome Analysis of Dopamine Neuron Glutamatergic Connections in Forebrain Regions
Mingote, S., Chuhma, N., Kusnoor, S. V., Field, B. C., Deutch, A. Y., & Rayport, S. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1674-15.2015 · Cited by 93 · see citing works
“…connections are weaker than those found in NAc SPNs. Weaker connections might identify release sites where glutamate cotransport potentiates dopamine release through vesicular synergy by increasing the packing of dopamine into vesicles (El Mestikawy et al., 2011; Hnasko and Edwards, 2012).”
BackgroundDuo, Y., Yang, L., Chen, C., Liu, B., Wang, X., Zeng, X., & Chen, H. (2017) · RSC Advances · doi:10.1039/c7ra05135b · Cited by 96 · see citing works
Multi-transmitter neurons in the mammalian central nervous system
Granger, A. J., Wallace, M. L., & Sabatini, B. L. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.04.007 · Cited by 95 · see citing works
Neuronal Depolarization Drives Increased Dopamine Synaptic Vesicle Loading via VGLUT
Aguilar, J. I., Dunn, M., Mingote, S., Karam, C. S., Farino, Z. J., Sonders, M. S., Choi, S. J., Grygoruk, A., Zhang, Y., Cela, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.038 · Cited by 91 · see citing works
“dynamically modulates both vesicular DpH and quantal size (Hnasko and Edwards, 2012).”
InfluentialRelevance of interactions between dopamine and glutamate neurotransmission in schizophrenia
Buck, S. A., Erickson-Oberg, M. Q., Logan, R. W., & Freyberg, Z. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01649-w · Cited by 92 · see citing works
“It has since been demonstrated that more than one neurotransmitter can be released from a single neuron [65, 66].”
BackgroundEmerging roles of Na+/H+ exchangers in epilepsy and developmental brain disorders
Zhao, H., Carney, K. E., Falgoust, L., Pan, J. W., Sun, D., & Zhang, Z. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.02.002 · Cited by 87 · see citing works
Krishnan, A., & Schiöth, H. B. (2015) · Journal of Experimental Biology · doi:10.1242/jeb.110312 · Cited by 81 · see citing works
Lack of Evidence for Vesicular Glutamate Transporter Expression in Mouse Astrocytes
Li, D., Hérault, K., Silm, K., Evrard, A., Wojcik, S. M., Oheim, M., Herzog, É., & Ropert, N. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3667-12.2013 · Cited by 86 · see citing works
“, 2005), may contribute to glutamate cotransmission (Trudeau and Gutierrez, 2007; Hnasko and Edwards, 2012) and facilitate the vesicular storage of cotransmitters (Gras et al.”
BackgroundInchauspe, C. G., Urbano, F. J., Guilmi, M. N. D., & Uchitel, O. D. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2566-16.2017 · Cited by 85 · see citing works
“It is known that synaptic vesicles are acidic, and it is postulated that acidification of the synaptic cleft during neurotransmission might activate ASICs (Palmer et al., 2003; Hnasko and Edwards, 2012).”
BackgroundWu, S. J., Yi, E., Manca, M., Javaid, H., Lauer, A. M., & Glowatzki, E. (2020) · eLife · doi:10.7554/elife.52419 · Cited by 83 · see citing works
Distinct Modes of Dopamine and GABA Release in a Dual Transmitter Neuron
Borisovska, M., Bensen, A. L., Chong, G., & Westbrook, G. L. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4342-12.2013 · Cited by 83 · see citing works
“The functional dual transmitter phenotype Although dual transmitter neurons containing dopamine and either glutamate or GABA occur in multiple brain regions (Hnasko and Edwards, 2012), the spatiotemporal characteristics of their (co)release is only beginning to be explored (Chuhma et al.”
BackgroundInfluentialBertels, H., Vicente-Ortiz, G., Kanbi, K. E., & Takeoka, A. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01067-9 · Cited by 81 · see citing works
Chuhma, N., Mingote, S., Kalmbach, A., Yetnikoff, L., & Rayport, S. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.07.002 · Cited by 82 · see citing works
“VGLUT2-mediated glutamate uptake dissipates the vesicular electrical gradient enabling further activity of the vesicular proton pump, vesicular acidification and DA packing (47, 63, 98).”
BackgroundUpmanyu, 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
“Corelease of multiple neurotransmitters from the same vesicle Release of multiple neurotransmitters from the same neuron or synapse is well documented (El Mestikawy et al., 2011; Granger et al., 2017; Hnasko and Edwards, 2012).”
BackgroundIs Aspartate an Excitatory Neurotransmitter?
Herring, B. E., Silm, K., Edwards, R. H., & Nicoll, R. A. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0524-15.2015 · Cited by 72 · see citing works
“…glutamate, serotonin and glutamate, and acetylcholine and glutamate, recent evidence has suggested costorage in the same vesicles, but it remains unclear whether this is always the case (Gras et al., 2008; Hnasko et al., 2010; Hnasko and Edwards, 2012; Tritsch et al., 2012; Nelson et al., 2014).”
BackgroundSelf-citationCorelease of Dopamine and GABA by a Retinal Dopaminergic Neuron
Hirasawa, H., Betensky, R. A., & Raviola, E. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.2213-12.2012 · Cited by 73 · see citing works
“In the CNS, there is convincing evidence for colocalization of dopamine (DA) with other low-molecular-mass transmitters that act on ionotropic postsynaptic receptors and therefore convey faster excitatory signals to the postsynaptic cell (Seal and Edwards, 2006; Hnasko and Edwards, 2012).”
BackgroundBhavsar, D., Gajjar, J., & Sawant, K. K. (2018) · Microporous and Mesoporous Materials · doi:10.1016/j.micromeso.2018.12.026 · Cited by 70 · see citing works
Tien, N.-W., Kim, T., & Kerschensteiner, D. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.025 · Cited by 67 · see citing works
“In recent years, however, it has become clear that the output of neurons can be more diverse (Hnasko and Edwards, 2012; Vaaga et al., 2014).”
BackgroundTarget 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
Modulation of synaptic function through the α-neurexin–specific ligand neurexophilin-1
Born, G., Breuer, D., Wang, S., Rohlmann, A., Coulon, P., Vakili, P., Reißner, C., Kiefer, F., Heine, M., Pape, H., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1312112111 · Cited by 67 · see citing works
“Because GABAR blockers are effective at transgenic excitatory synapses, we conclude that ambient GABA is available in these contacts, either by co-release with Glu or by spillover from neighbored GABAergic terminals (52, 53).”
BackgroundAre vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?
Liefferinge, J. V., Massie, A., Portelli, J., Giovanni, G. D., & Smolders, I. J. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00139 · Cited by 65 · see citing works
“…been suggested to modulate vesicular transport: (1) influencing the membrane potential ( (cid:2) ψ ) by cation and anion fluxes and (2) a direct interaction between the heterotrimeric G-protein, G α o2 and VNTs (Omote et al., 2011; Blakely and Edwards, 2012; Hnasko and Edwards, 2012) ( Figure 2 ).”
InfluentialResiniferatoxin for Pain Treatment: An Interventional Approach to Personalized Pain Medicine
Iadarola, M. J., & Gonnella, G. L. (2013) · The Open Pain Journal · doi:10.2174/1876386301306010095 · Cited by 61 · see citing works
Vesicular Neurotransmitter Transporters
Anne, C., & Gasnier, B. (2014) · Current topics in membranes · doi:10.1016/b978-0-12-800223-0.00003-7 · Cited by 60 · see citing works
“The biology of vesicular neurotransmitter transporters and their role in synaptic transmission have been covered in several recent reviews (Edwards, 2007; El Mestikawy, Wallen-Mackenzie, Fortin, Descarries, & Trudeau, 2011; Hnasko & Edwards, 2012).”
BackgroundMeng, D., Li, H.-Q., Deisseroth, K. A., Leutgeb, S., & Spitzer, N. C. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1801598115 · Cited by 61 · see citing works
Balaram, P., Hackett, T. A., & Kaas, J. H. (2013) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2013.02.007 · Cited by 60 · see citing works
“…anatomical and functional characteristics of driving and modulating projections, independent of the source of the projection, that also match the physiological properties of VGLUT1 and VGLUT2 within a synapse (Blakely and Edwards, 2012; Fremeau et al, 2004; Hnasko and Edwards, 2012 for review).”
BackgroundSynaptic and circuit functions of multitransmitter neurons in the mammalian brain
Wallace, M. L., & Sabatini, B. L. (2023) · Neuron · doi:10.1016/j.neuron.2023.06.003 · Cited by 59 · see citing works
Octopamine neuron dependent aggression requires dVGLUT from dual-transmitting neurons
Sherer, L. M., Catudio-Garrett, E. L., Morgan, H. R., Brewer, E. D., Sirrs, L. A., Shearin, H. K., Williams, J. L., McCabe, B. D., Stowers, R. S., & Certel, S. J. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1008609 · Cited by 56 · see citing works
“In addition, one vesicular neurotransmitter transporter can increase the packaging of the other neurotransmitter into the same synaptic vesicle (SV), a process called vesicular synergy [4, 12, 13].”
BackgroundWarlow, S. M., Singhal, S. M., Hollon, N. G., Faget, L. C., Dowlat, D. S., Zell, V., Hunker, A. C., Zweifel, L. S., & Hnasko, T. S. (2023) · Neuron · doi:10.1016/j.neuron.2023.11.002 · Cited by 59 · see citing works
Self-citationInhibitory co-transmission from midbrain dopamine neurons relies on presynaptic GABA uptake
Melani, R., & Tritsch, N. X. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110716 · Cited by 56 · see citing works
Wu, M. V., & Tollkühn, J. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2017.07.001 · Cited by 55 · see citing works
“Other neurotransmitters, such as dopamine, can be expressed in Vgat/Vglut2-negative cells, and may contribute important modulatory functions (Hnasko and Edwards, 2012).”
BackgroundNanosensors for neurotransmitters
Polo, E., & Kruss, S. (2015) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-015-9160-x · Cited by 53 · see citing works
“[3 7]”
BackgroundArchitecture of the subthalamic nucleus
Prasad, A. A., & Wallén‐Mackenzie, Å. (2024) · Communications Biology · doi:10.1038/s42003-023-05691-4 · Cited by 59 · see citing works
“Both VGLUT1 and VGLUT2 proteins have been identi fi ed as glutamate transporters in the membrane of pre-synaptic vesicles and are therefore considered as molecular markers de fi ning the glutamatergic phenotype of neurons 82 – 84 .”
BackgroundExtrasynaptic release of GABA and dopamine by retinal dopaminergic neurons
Hirasawa, H., Contini, M., & Raviola, E. (2015) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2014.0186 · Cited by 53 · see citing works
Paradoxical network excitation by glutamate release from VGluT3+ GABAergic interneurons
Pelkey, K. A., Calvigioni, D., Fang, C., Vargish, G., Ekins, T., Auville, K., Wester, J. C., Lai, M., Mackenzie-Gray Scott, C., Yuan, X., et al. (2020) · eLife · doi:10.7554/elife.51996 · Cited by 46 · see citing works
Presynaptic HCN Channels Regulate Vesicular Glutamate Transport
Huang, H. Y., & Trussell, L. O. (2014) · Neuron · doi:10.1016/j.neuron.2014.08.046 · Cited by 50 · see citing works
“TheDmH + reflects both electrical potential (Dc) and chemical pH gradients (DpH); transporters for different neurotransmitters depend to differing extents on Dc and DpH due to the charge on the substrate and the stoichiometry of coupling to H (Hnasko and Edwards, 2012).”
Von Economo Neurons and Fork Cells: A Neurochemical Signature Linked to Monoaminergic Function
Dijkstra, A. A., Lin, L., Nana, A. L., Gaus, S. E., & Seeley, W. W. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw358 · Cited by 49 · see citing works
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“The V-ATPase hub contained the majority of the V-ATPase subunits required for both SV and endosome acidification (23).”
BackgroundDivergent properties and independent regulation of striatal dopamine and GABA co-transmission
Zych, S. M., & Ford, C. P. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110823 · Cited by 46 · see citing works
“However, it is unknown whether all DA neurons contribute to GABA signaling or whether it is restricted to subpopulations like glutamate co-transmission from DA neurons (Hnasko and Edwards, 2012; Zhang et al., 2015; Silm et al., 2019).”
BackgroundDopamine neuron dependent behaviors mediated by glutamate cotransmission
Mingote, S., Chuhma, N., Kalmbach, A., Thomsen, G. M., Wang, Y., Mihali, A., Sferrazza, C. E., Zucker-Scharff, I., Siena, A.-C., Welch, M. G., et al. (2017) · eLife · doi:10.7554/elife.27566 · Cited by 46 · see citing works
Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration
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“Glutamate uptake depends mainly on Dw , whereas the activity of the vesicular GABA transporter VGAT depends on both parameters (Hnasko & Edwards, 2012).”
Rapid purification and metabolomic profiling of synaptic vesicles from mammalian brain
Chantranupong, L., Saulnier, J. L., Wang, W., Jones, D. R., Pacold, M. E., & Sabatini, B. L. (2020) · eLife · doi:10.7554/elife.59699 · Cited by 41 · see citing works
“Further increasing the complexity, 32 these neurotransmitters may be packaged within the same or different SV pools or released from distinct 33 axon terminals (Hnasko and Edwards, 2012; Saunders et al., 2015).”
BackgroundDopamine neurons exhibit emergent glutamatergic identity in Parkinson’s disease
Steinkellner, T., Conrad, W. S., Kovács, I., Rissman, R. A., Lee, E. B., Trojanowski, J. Q., Freyberg, Z., Roy, S., Luk, K. C., Lee, V. M., et al. (2021) · Brain · doi:10.1093/brain/awab373 · Cited by 47 · see citing works
Self-citationG Protein-Coupled Receptors in Myelinating Glia
Mogha, A., D’Rozario, M., & Monk, K. R. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.09.002 · Cited by 44 · see citing works
“accordingly, glutamate receptors have been studied in great detail with regard to their key roles in synaptic transmission, synapse formation, axon guidance, and development of neuronal circuits [6,7].”
BackgroundRegulation of synaptic vesicle acidification at the neuronal synapse
Gowrisankaran, S., & Milosevic, I. (2020) · IUBMB Life - A Journal of the International Union of Biochemistry and Molecular Biology · doi:10.1002/iub.2235 · Cited by 28 · see citing works
“The key components that execute SV acidification and neurotransmitter filling are the proton-pumping vacuolar H-ATPases (vATPases) and the vesicular neurotransmitter transporters.(7,8) These two groups of proteins initiate distinct processes: the vATPases form a proton electrochemical gradient (ΔμH+) across the membra…”
BackgroundDopamine Neurons That Cotransmit Glutamate, From Synapses to Circuits to Behavior
Eskenazi, D., Malave, L. B., Mingote, S., Yetnikoff, L., Ztaou, S., Velicu, V., Rayport, S., & Chuhma, N. (2021) · Frontiers in Neural Circuits · doi:10.3389/fncir.2021.665386 · Cited by 44 · see citing works
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Jenstad, M., & Chaudhry, F. A. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00199 · Cited by 44 · see citing works
Neuromodulator and neuropeptide sensors and probes for precise circuit interrogation in vivo
Muir, J., Anguiano, M., & Kim, C. K. (2024) · Science · doi:10.1126/science.adn6671 · Cited by 45 · see citing works
“As an alternative, optogenetic stimulation of the subset of neurons that produce a given neuro-modulator or neuropeptide can be used to drive neurochemical release ( 110 ), but this approach is confounded by the fact that most neurons co-release multiple neuromodulators and neuropeptides ( 111 ).”
Background
- Authors
- Hnasko, T. S., & Edwards, R. H.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Annual Review of Physiology
- Publisher
- Annual Reviews
- Published
- 2012-03-17
- Volume
- 74
- Issue
- 1
- Pages
- 225-243
- ISSN
- 0066-4278 (ISSN-L)
- 1545-1585
- PMC
- PMC4090038
- OpenAlex
- W2136916973
- Cited by
- 284
- References
- 117
- Citations by year
- 2026: 11 · 2025: 7 · 2024: 27 · 2023: 15 · 2022: 22 · 2021: 19 · 2020: 20 · 2019: 18 · 2018: 22 · 2017: 24 · 2016: 26 · 2015: 24 · 2014: 27 · 2013: 14 · 2012: 8
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH050712)
- National Institute on Drug Abuse (K01DA026504)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- synaptic vesicles, vesicular uptake, vesicle sorting, synaptic transmission, neurotransmitter identity
- MeSH terms
- Acetylcholine, Animals, Anions, Cations, Chlorides, gamma-Aminobutyric Acid, Humans, Hydrogen-Ion Concentration, Synaptic Transmission, Protons, Synaptic Vesicles, Biogenic Monoamines, Neurotransmitter Agents, Glutamic Acid, Vesicular Neurotransmitter Transport Proteins
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.
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