The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons
Open accessAbstract
Neuromodulatory control by oxytocin is essential to a wide range of social, parental and stress-related behaviours. Autism spectrum disorders (ASD) are associated with deficiencies in oxytocin levels and with genetic alterations of the oxytocin receptor (OXTR). Thirty years ago, Mühlethaler et al. found that oxytocin increases the firing of inhibitory hippocampal neurons, but it remains unclear how elevated inhibition could account for the ability of oxytocin to improve information processing in the brain. Here we describe in mammalian hippocampus a simple yet powerful mechanism by which oxytocin enhances cortical information transfer while simultaneously lowering background activity, thus greatly improving the signal-to-noise ratio. Increased fast-spiking interneuron activity not only suppresses spontaneous pyramidal cell firing, but also enhances the fidelity of spike transmission and sharpens spike timing. Use-dependent depression at the fast-spiking interneuron-pyramidal cell synapse is both necessary and sufficient for the enhanced spike throughput. We show the generality of this novel circuit mechanism by activation of fast-spiking interneurons with cholecystokinin or channelrhodopsin-2. This provides insight into how a diffusely delivered neuromodulator can improve the performance of neural circuitry that requires synapse specificity and millisecond precision.
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In the citing paper
“In contrast to hippocampal CA2, oxytocin does not depolarize CA1 pyramidal cells but instead activates parvalbumin-positive fast-spiking interneurons”
From Oxytocin, Neural Plasticity, and Social Behavior (2021) · cites this paper as Owen et al. 2013
Experimental — accuracy not yet measuredIn the citing paper
“OTR and V1aR are classic neuromodulators, mediating both short- and long-term changes in neural and hence behavioral outcomes (Owen et al., 2013).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Owen et al., 2013
In the citing paper
“Oxytocin is thought to modulate neural activity by affecting the excitatory/inhibitory balance and also seems to improve the signal-to-noise ration by stimulating fast spiking parvalbumin inter-neuron activity (Owen et al. 2013).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Owen et al. 2013
In the citing paper
“Together with recent findings showing that OT can increase processing efficiency at the neuronal level by optimizing signal-to-noise during cell firing43”
From Intranasal oxytocin enhances connectivity in the neural circuitry supporting social motivation and social perception in children with autism (2016) · cites this paper as [43]
In the citing paper
“these results show that in ASD, OT may not only serve to enhance neural activity to “preferred” stimuli, but also improve communication among brain regions involved in social motivation and perception.”
From Intranasal oxytocin enhances connectivity in the neural circuitry supporting social motivation and social perception in children with autism (2016) · cites this paper as [43]
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Citations
Cites
Interneurons of the hippocampus
Freund, T. F., & Buzsáki, G. (1998) · Hippocampus · doi:10.1002/(sici)1098-1063(1996)6:4 · Cited by 3,478
Oxytocin improves “mind-reading” in humans
Domes, G., Heinrichs, M., Michel, A., Berger, C., & Herpertz, S. C. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.07.015 · Cited by 1,298 · cited 6×
“TGOT was simulated by (1) reducing the evoked somatic IPSC conductance to 60% of “baseline”, while sparing the evoked EPSC and the dendritic IPSC, (2) doubling the spontaneous IPSC amplitude, and (3) increasing the spontaneous IPSC rate from 5 Hz to 35 Hz.”
BackgroundMethodInfluentialVerret, L., Mann, E. O., Hang, G. B., Barth, A. M. I., Cobos, I., Ho, K., Devidze, N., Masliah, E., Kreitzer, A. C., Mody, I., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.046 · Cited by 1,216
A Developmental Switch in the Response of DRG Neurons to ETS Transcription Factor Signaling
Hippenmeyer, S., Pecho‐Vrieseling, E., Sigrist, M., Portmann, T., Laengle, C., Ladle, D. R., & Arber, S. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030159 · Cited by 1,111
Enforcement of Temporal Fidelity in Pyramidal Cells by Somatic Feed-Forward Inhibition
Pouille, F., & Scanziani, M. (2001) · Science · doi:10.1126/science.1060342 · Cited by 1,097
Evoked axonal oxytocin release in the central amygdala attenuates fear response
Knobloch, H. S., Charlet, A., Hoffmann, L. C., Eliava, M., Khrulev, S., Cetin, A. H., Osten, P., Schwarz, M. K., Seeburg, P. H., Stoop, R., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.030 · Cited by 1,049
Oxytocin in the Medial Amygdala is Essential for Social Recognition in the Mouse
Ferguson, J. N., Aldag, J. M., Insel, T. R., & Young, L. J. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-20-08278.2001 · Cited by 1,043 · cited 9×
“TGOT increased the spontaneous firing of presynaptic FSIs and also diminished the FSI-pyramidal cell unitary IPSC, without affecting RS interneurons (Fig 3a,b).”
BackgroundMethodInfluentialIntranasal oxytocin improves emotion recognition for youth with autism spectrum disorders.
Guastella, A. J., Einfeld, S. L., Gray, K. M., Rinehart, N. J., Tonge, B. J., Lambert, T. J., & Hickie, I. B. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.020 · Cited by 962
Plasma oxytocin levels in autistic children
Modahl, C., Green, L. A., Fein, D., Morris, M., Waterhouse, L., Feinstein, C., & Levin, H. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00439-3 · Cited by 728
Instantaneous Modulation of Gamma Oscillation Frequency by Balancing Excitation with Inhibition
Atallah, B. V., & Scanziani, M. (2009) · Neuron · doi:10.1016/j.neuron.2009.04.027 · Cited by 614
Common circuit defect of excitatory-inhibitory balance in mouse models of autism
Gogolla, N., LeBlanc, J. J., Quast, K. B., Südhof, T. C., Fagiolini, M., & Hensch, T. K. (2009) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-009-9023-x · Cited by 610
Yoshida, M., Takayanagi, Y., Inoue, K., Kimura, T., Young, L. J., Onaka, T., & Nishimori, K. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5593-08.2009 · Cited by 608
Activation of specific interneurons improves V1 feature selectivity and visual perception
Lee, S.-H., Kwan, A. C., Zhang, S., Phoumthipphavong, V., Flannery, J. G., Masmanidis, S. C., Taniguchi, H., Huang, Z. J., Zhang, F., Boyden, E. S., et al. (2012) · Nature · doi:10.1038/nature11312 · Cited by 593
Searching for ways out of the autism maze: genetic, epigenetic and environmental clues
Persico, A. M., & Bourgeron, T. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.05.010 · Cited by 575
Positive Association of the Oxytocin Receptor Gene (OXTR) with Autism in the Chinese Han Population
Wu, S., Jia, M., Ruan, Y., Liu, J., Guo, Y., Mei, S., Gong, X., Zhang, Y., Yang, X., & Zhang, D. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.03.013 · Cited by 565
Presynaptic Specificity of Endocannabinoid Signaling in the Hippocampus
Wilson, R. I., Kunos, G., & Nicoll, R. A. (2001) · Neuron · doi:10.1016/s0896-6273(01)00372-5 · Cited by 543
Galarreta, M., & Hestrin, S. (1998) · Nature Neuroscience · doi:10.1038/2822 · Cited by 436
Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential
Shu, Y., Hasenstaub, A. R., Duque, A., Yu, Y., & McCormick, D. A. (2006) · Nature · doi:10.1038/nature04720 · Cited by 397
Madison, D. V., & Nicoll, R. A. (1986) · The Journal of Physiology · doi:10.1113/jphysiol.1986.sp016006 · Cited by 391
Oxytocin improves long-lasting spatial memory during motherhood through MAP kinase cascade
Tomizawa, K., Iga, N., Lü, Y.-F., Moriwaki, A., Matsushita, M., Li, S., Miyamoto, O., Itano, T., & Matsui, H. (2003) · Nature Neuroscience · doi:10.1038/nn1023 · Cited by 372 · cited 5×
“specified), and (3) multiple ‘spontaneous’ IPSCs onto the soma with randomly distributed amplitudes and timing.”
BackgroundInfluentialAnagnostou, E., Soorya, L., Chaplin, W., Bartz, J., Halpern, D., Wasserman, S., Wang, A. T., Pepa, L., Tanel, N., Kushki, A., et al. (2012) · Molecular Autism · doi:10.1186/2040-2392-3-16 · Cited by 350
Unreliable evoked responses in autism
Dinstein, I., Heeger, D. J., Lorenzi, L., Minshew, N. J., Malach, R., & Behrmann, M. (2012) · Neuron · doi:10.1016/j.neuron.2012.07.026 · Cited by 318
Segal, M., & Bloom, F. E. (1976) · Brain Research · doi:10.1016/0006-8993(76)90141-4 · Cited by 314
Motherhood improves learning and memory
Kinsley, C. H., Madonia, L., Gifford, G. W., Tureski, K., Griffin, G. R., Lowry, C., Williams, J., Collins, J., McLearie, H., & Lambert, K. G. (1999) · Nature · doi:10.1038/45957 · Cited by 297
Efficacy and Stability of Quantal GABA Release at a Hippocampal Interneuron–Principal Neuron Synapse
Kraushaar, U., & Jonas, P. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-15-05594.2000 · Cited by 281
Distinct timing in the activity of cannabinoid-sensitive and cannabinoid-insensitive basket cells
Glickfeld, L. L., & Scanziani, M. (2006) · Nature Neuroscience · doi:10.1038/nn1688 · Cited by 222
Excitatory actions of norepinephrine on multiple classes of hippocampal CA1 interneurons
Bergles, D. E., Doze, V. A., Madison, D. V., & Smith, S. J. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-02-00572.1996 · Cited by 195
Commissural projection to the dentate gyrus of the rat: evidence for feed-forward inhibition
Buzsáki, G., & Eidelberg, E. (1981) · Brain Research · doi:10.1016/0006-8993(81)90413-3 · Cited by 179
An arithmetic rule for spatial summation of excitatory and inhibitory inputs in pyramidal neurons
Jiang, H., Wang, X.-D., Dan, Y., Poo, M., & Zhang, X.-H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912022106 · Cited by 150
Synaptic localization of adrenergic disinhibition in the rat hippocampus
Doze, V. A., Cohen, G. A., & Madison, D. V. (1991) · Neuron · doi:10.1016/0896-6273(91)90229-s · Cited by 123
Cell type–specific gating of perisomatic inhibition by cholecystokinin
Földy, C., Lee, S. Y., Szabadics, J., Neu, A. D., & Soltész, I. (2007) · Nature Neuroscience · doi:10.1038/nn1952 · Cited by 121
Mühlethaler, M., Charpak, S., & Dreifuss, J. J. (1984) · Brain Research · doi:10.1016/0006-8993(84)90921-1 · Cited by 109
Zaninetti, M., & Raggenbass, M. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00290.x · Cited by 82
Local Control of Postinhibitory Rebound Spiking in CA1 Pyramidal Neuron Dendrites
Ascoli, G. A., Gasparini, S., Medinilla, V., & Migliore, M. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.4066-09.2010 · Cited by 75
Kuo, S. P., & Trussell, L. O. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.039 · Cited by 57
Alberi, S., Dreifuss, J. J., & Raggenbass, M. (1997) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1997.tb01690.x · Cited by 44
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Robertson, C. E., & Baron-Cohen, S. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.112 · Cited by 1,157
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Metadata
- Authors
- Owen, S. F., Tuncdemir, S. N., Bader, P. L., Tirko, N. N., Fishell, G., & Tsien, R. W.
- Affiliations
- Stanford Medicine (US)
- New York University (US)
- Corresponding author
- Tsien, Richard W.
- Venue
- Nature
- Published
- 2013-08
- Volume
- 500
- Issue
- 7463
- Pages
- 458-462
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5283693
- OpenAlex
- W2008069212
- Cited by
- 339
- References
- 36
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 21 · 2023: 26 · 2022: 22 · 2021: 28 · 2020: 21 · 2019: 23 · 2018: 35 · 2017: 35 · 2016: 33 · 2015: 37 · 2014: 26 · 2013: 7
- FWCI
- 51.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of Mental Health (F31MH084430, MH071739, MH064070, R01MH071739, R37MH071739)
- National Institute of Neurological Disorders and Stroke (NS024067, R01NS024067, R01NS074785)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- oxytocin, hippocampus, fast-spiking interneurons, signal-to-noise ratio, neuromodulation, synaptic depression, pyramidal neurons, cholecystokinin, channelrhodopsin-2, autism spectrum disorder, oxytocin receptor, inhibitory interneurons
- MeSH terms
- Action Potentials, Animals, Brain, Cholecystokinin, Glycine, Hippocampus, Interneurons, Neural Pathways, Synaptic Transmission, Oxytocin, Rhodopsin, Synapses, Threonine, Pyramidal Cells, Receptors, Oxytocin, Excitatory Postsynaptic Potentials, Feedback, Physiological, Mice, Rats
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