NMDA receptors induce somatodendritic secretion in hypothalamic neurones of lactating female rats
Abstract
Many neurones in the mammalian brain are known to release the content of their vesicles from somatodendritic locations. These vesicles usually contain retrograde messengers that modulate network properties. The back‐propagating action potential is thought to be the principal physiological stimulus that evokes somatodendritic release. In contrast, here we show that calcium influx through NMDA receptor (NMDAR) channels, in the absence of postsynaptic cell firing, is also able to induce vesicle fusion from non‐synaptic sites in nucleated outside‐out patches of dorsomedial supraoptic nucleus (SON) neurones of adult female rats, in particular during their reproductive stages. The physiological significance of this mechanism was characterized in intact brain slices, where NMDAR‐mediated release of oxytocin was shown to retrogradely inhibit presynaptic GABA release, in the absence of postsynaptic cell firing. This implies that glutamatergic synaptic input in itself is sufficient to elicit the release of oxytocin, which in turn acts as a retrograde messenger leading to the depression of nearby GABA synapses. In addition, we found that during lactation, when oxytocin demand is high, NMDA‐induced oxytocin release is up‐regulated compared to that in non‐reproductive rats. Thus, in the hypothalamus, local signalling back and forth between pre‐ and postsynaptic compartments and between different synapses may occur independently of the firing activity of the postsynaptic neurone.
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Postsynaptic NMDARs regulate excitability and trigger somatodendritic oxytocin release.
“Postsynaptic NMDARs also regulate excitability48,49 and trigger somatodendritic oxytocin release47.”
From Neural circuitry for maternal oxytocin release induced by infant cries (2023) · cites this paper as [47]
Oxytocin-neuron NMDARs can be activated without postsynaptic spiking, suggesting that prolonged subthreshold activation of oxytocin cells is sufficient to induce NMDAR-dependent inhibitory LTD.
“Oxytocin-neuron NMDARs can be activated without the need for postsynaptic spiking47, suggesting that even if PIL inputs are too weak to trigger action potentials, prolonged subthreshold activation of oxytocin cells is sufficient to induce NMDAR-dependent inhibitory LTD.”
From Neural circuitry for maternal oxytocin release induced by infant cries (2023) · cites this paper as [47]
Cites
The molecular logic of endocannabinoid signalling
Piomelli, D. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1247 · Cited by 1,957 · see citing works
Role of Endogenous Cannabinoids in Synaptic Signaling
Freund, T. F., Katona, I., & Piomelli, D. (2003) · Physiological Reviews · doi:10.1152/physrev.00004.2003 · Cited by 1,568 · see citing works
Di, S., Malcher‐Lopes, R., Halmos, K. C., & Tasker, J. G. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-12-04850.2003 · Cited by 801 · see citing works
Patch-clamp techniques for time-resolved capacitance measurements in single cells
Lindau, M., & Neher, E. (1988) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00582306 · Cited by 674 · see citing works
Heterosynaptic LTD of Hippocampal GABAergic Synapses
Chevaleyre, V., & Castillo, P. E. (2003) · Neuron · doi:10.1016/s0896-6273(03)00235-6 · Cited by 647 · see citing works
Control of Glutamate Clearance and Synaptic Efficacy by Glial Coverage of Neurons
Oliet, S. H. R., Piet, R., & Poulain, D. A. (2001) · Science · doi:10.1126/science.1059162 · Cited by 623 · see citing works
Burnashev, N., Zhou, Z., Neher, E., & Sakmann, B. J. (1995) · The Journal of Physiology · doi:10.1113/jphysiol.1995.sp020738 · Cited by 450 · see citing works
Self-citationDendrites of hypothalamic magnocellular neurons release neurohypophysial peptides by exocytosis
Pow, D. V., & Morris, J. F. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90091-2 · Cited by 446 · see citing works
Intracellular calcium stores regulate activity-dependent neuropeptide release from dendrites
Ludwig, M., Sabatier, N., Bull, P. M., Landgraf, R., Dayanithi, G., & Leng, G. (2002) · Nature · doi:10.1038/nature00822 · Cited by 346 · see citing works
Neumann, I., Russell, J. A., & Landgraf, R. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90285-n · Cited by 337 · see citing works
Physiological pathways regulating the activity of magnocellular neurosecretory cells
Leng, G., Brown, C. H., & Russell, J. A. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00072-0 · Cited by 312 · see citing works
Serotonin and the regulation of mammalian circadian rhythmicity
Morin, L. P. (1999) · Annals of Medicine · doi:10.3109/07853899909019259 · Cited by 286 · see citing works
Inhibition of endocytosis by elevated internal calcium in a synaptic terminal
von Gersdorff, H., & Matthews, G. (1994) · Nature · doi:10.1038/370652a0 · Cited by 256 · see citing works
Analysis of Relations between NMDA Receptors and GABA Release at Olfactory Bulb Reciprocal Synapses
Chen, W. R., Xiong, W., & Shepherd, G. M. (2000) · Neuron · doi:10.1016/s0896-6273(00)81065-x · Cited by 235 · see citing works
Sather, W. A., Dieudonné, S., MacDonald, J. F., & Ascher, P. (1992) · The Journal of Physiology · doi:10.1113/jphysiol.1992.sp019148 · Cited by 234 · see citing works
Brussaard, A. B., Kits, K. S., Baker, R. E., Willems, W. P. A., Leyting-Vermeulen, J. W., Voorn, P., Smit, A. B., Bicknell, R. J., & Herbison, A. E. (1997) · Neuron · doi:10.1016/s0896-6273(00)80401-8 · Cited by 228 · see citing works
Self-citationTalking back: dendritic neurotransmitter release
Ludwig, M., & Pittman, Q. J. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00072-9 · Cited by 210 · see citing works
Jaffe, E. H., Marty, A., Schulte, A., & Chow, R. H.-P. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-10-03548.1998 · Cited by 200 · see citing works
Liu, R., Jolas, T., & Aghajanian, G. K. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02468-9 · Cited by 197 · see citing works
Paracrine neurotransmission in the CNS: involvement of 5-HT
Bunin, M. A., & Wightman, R. M. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01410-1 · Cited by 187 · see citing works
Kombian, S. B., Mouginot, D., & Pittman, Q. J. (1997) · Neuron · doi:10.1016/s0896-6273(00)80971-x · Cited by 186 · see citing works
The significance of action potential bursting in the brain reward circuit
Cooper, D. (2002) · Neurochemistry International · doi:10.1016/s0197-0186(02)00068-2 · Cited by 178 · see citing works
Inhibition of Interneuron Firing Extends the Spread of Endocannabinoid Signaling in the Cerebellum
Kreitzer, A. C., Carter, A. G., & Regehr, W. G. (2002) · Neuron · doi:10.1016/s0896-6273(02)00695-5 · Cited by 168 · see citing works
Hou-Yu, A., Lamme, A., Zimmerman, E. A., & Silverman, A. (2008) · Neuroendocrinology · doi:10.1159/000124651 · Cited by 160 · see citing works
Summerlee, A. J. S. (1981) · The Journal of Physiology · doi:10.1113/jphysiol.1981.sp013967 · Cited by 154 · see citing works
Bekkers, J. M. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.t01-1-00593.x · Cited by 147 · see citing works
Neumann, I. D., Koehler, E., Landgraf, R., & Summy‐Long, J. Y. (1994) · Endocrinology · doi:10.1210/endo.134.1.8275928 · Cited by 146 · see citing works
Hirasawa, M., Schwab, Y., Natah, S. S., Hillard, C. J., Mackie, K., Sharkey, K. A., & Pittman, Q. J. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.066159 · Cited by 143 · see citing works
Calcium Influx through NMDA Receptors Directly Evokes GABA Release in Olfactory Bulb Granule Cells
Halabisky, B., Friedman, D., Radojicic, M., & Strowbridge, B. W. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-13-05124.2000 · Cited by 141 · see citing works
Zilberter, Y., Kaiser, K. M. M., & Sakmann, B. J. (1999) · Neuron · doi:10.1016/s0896-6273(00)81044-2 · Cited by 140 · see citing works
Chen, Q. X., & Wong, R. K. S. (1995) · The Journal of Physiology · doi:10.1113/jphysiol.1995.sp020522 · Cited by 140 · see citing works
Brussaard, A. B., Dévay, P., Leyting-Vermeulen, J. W., & Kits, K. S. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.0513v.x · Cited by 131 · see citing works
Self-citationArtalejo, C. R., Elhamdani, A., & Palfrey, H. C. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082658499 · Cited by 126 · see citing works
Brussaard, A. B., Kits, K. S., & Vlieger, T. A. D. (1996) · The Journal of Physiology · doi:10.1113/jphysiol.1996.sp021783 · Cited by 122 · see citing works
Self-citationRozov, A., Zilberter, Y., Wollmuth, L. P., & Burnashev, N. (1998) · The Journal of Physiology · doi:10.1111/j.1469-7793.1998.361bh.x · Cited by 114 · see citing works
Self-citationContribution of transient receptor potential channels to the control of GABA release from dendrites
Munsch, T., Freichel, M., Flockerzi, V., & Pape, H. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2535311100 · Cited by 111 · see citing works
Galante, M., & Diana, M. A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.0403-04.2004 · Cited by 110 · see citing works
Oliet, S. H. R., & Poulain, D. A. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.00815.x · Cited by 109 · see citing works
Somatodendritic Secretion in Oxytocin Neurons Is Upregulated during the Female Reproductive Cycle
de Kock, C. P. J., Wierda, K. D. B., Bosman, L. W. J., Min, R., Koksma, J.-J., Mansvelder, H. D., Verhage, M., & Brussaard, A. B. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-07-02726.2003 · Cited by 103 · see citing works
Self-citationKonishi, H., & Nakajima, T. (1978) · PubMed · Cited by 102 · see citing works
Brussaard, A. B., & Herbison, A. E. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01540-4 · Cited by 100 · see citing works
Self-citationGrillner, P., & Mercuri, N. B. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00418-1 · Cited by 98 · see citing works
Role of dorsal raphe nucleus serotonin 5-HT1A receptor in the regulation of REM sleep
Monti, J. M., & Monti, D. (2000) · Life Sciences · doi:10.1016/s0024-3205(99)00649-9 · Cited by 74 · see citing works
Stern, J. E., Hestrin, S., & Armstrong, W. E. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.t01-1-00109.x · Cited by 68 · see citing works
Profile of Monoamine and Excitatory Amino Acid Release in Rat Supraoptic Nucleus over Parturition
Herbison, A. E., Voisin, D. L., Douglas, A. J., & Chapman, C. (1997) · Endocrinology · doi:10.1210/endo.138.1.4859 · Cited by 67 · see citing works
Morris, J. F., Christian, H., Ma, D., & Wang, H. (2000) · Experimental Physiology · doi:10.1111/j.1469-445x.2000.tb00016.x · Cited by 52 · see citing works
Ghetti, A., & Heinemann, S. F. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-08-02766.2000 · Cited by 46 · see citing works
Mansvelder, H. D., & Kits, K. S. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-01-00081.1998 · Cited by 46 · see citing works
Self-citationAl‐Ghoul, W. M., Meeker, R. B., & Greenwood, R. (1997) · Molecular Brain Research · doi:10.1016/s0169-328x(96)00205-7 · Cited by 43 · see citing works
Modulation of GABAergic transmission by endogenous glutamate in the rat supraoptic nucleus
Piet, R., Bonhomme, R., Theodosis, D. T., Poulain, D. A., & Oliet, S. H. R. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02611.x · Cited by 38 · see citing works
Expression and plasticity of glutamate receptors in the supraoptic nucleus of the hypothalamus
Pak, C. W., & Currás‐Collazo, M. (2002) · Microscopy Research and Technique · doi:10.1002/jemt.10017 · Cited by 28 · see citing works
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Eyal, G., Verhoog, M. B., Testa-Silva, G., Deitcher, Y., Lodder, J. C., Benavides-Piccione, R., Morales, J., DeFelipe, J., de Kock, C. P., Mansvelder, H. D., et al. (2016) · eLife · doi:10.7554/elife.16553 · Cited by 196 · see citing works
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- Authors
- De Kock, C. P. J., Burnashev, N., Lodder, J. C., Mansvelder, H. D., & Brussaard, A. B.
- Affiliations
- Vrije Universiteit Amsterdam (NL)
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2004-11
- Volume
- 561
- Issue
- 1
- Pages
- 53-64
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- OpenAlex
- W2138215802
- Cited by
- 50
- References
- 51
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 8 · 2013: 3 · 2012: 1
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- VU Research Portal (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- NMDA receptor, oxytocin release, hypothalamic neurons, lactation, retrograde signaling, GABA release, calcium influx, glutamatergic synaptic input, presynaptic inhibition
- MeSH terms
- Action Potentials, Animals, Calcium, Dendrites, Female, Hypothalamus, Lactation, Neuronal Plasticity, Neurons, Synapses, Synaptic Vesicles, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Rats, Wistar, Patch-Clamp Techniques, Glutamic Acid, Electric Capacitance, Rats
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