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
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“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
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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
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Bouchard-Cannon, P. (2018) · TSpace (University of Toronto)
The Contribution of Hippocampal Oxytocin Receptors to Social Memory Processing
Raam, T. (2018) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
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Faculty Opinions recommendation of Oxytocin transforms firing mode of CA2 hippocampal neurons.
Sajikumar, S., & Benoy, A. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734147277.793553360
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Attachment Stimuli Trigger Widespread Synchrony across Multiple BrainsPreprint
Shimon-Raz, O., Yeshurun, Y., Ulmer-Yaniv, A., Levinkron, A., Salomon, R., & Feldman, R. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.10.527970
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(2023) · International Journal of Public Health and Preventive Medicine · doi:10.38007/ijphpm.2023.040105
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Hidema, S., Nishimori, K., Otsuka, A., Horiai, M., Mizuno, K., Ono, T., Maejima, Y., & Shimomura, K. (2025) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2025.120263 · Cited by 1
Chamberland, S., Rosenberg, E. C., Nebet, E. R., Devinsky, O., & Tsien, R. W. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.26.672420
Fu, X., Shelkar, G. P., Coleman, E. M., Antonoudiou, P., Maguire, J. L., & Tasker, J. G. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.10.693563
Bertoni, A. (2019) · theses.fr (ABES) · doi:10.70675/d43fcf44zc66ez47a1zae43zd20439e2b233
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New regulators in oxytocin and vasopressin release : role of the endolysosomal two-pore channels
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“At the microcircuit level, oxytocin has been shown to reshape the excitatory - inhibitory balance by enhancing tonic inhibitory tone while suppressing phasic inhibition via use - dependent depression, effectively serving as a neural gain control and signal - to - noise regulator (5, 11).”
Circuit logic of oxytocin and vasopressin complementary actions
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“A similar population co-expressing OTR and V1b exists in CA2 neurons projecting to LS for excitatory amplification (Leroy et al., 2018), and CA3 targets for feedforward inhibition (Cymerblit-Sabba et al., 2023).”
InfluentialComparative atlas of PVN oxytocin and vasopressin systems reveals sex-conserved input–output wiring
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Endogenous oxytocin reconfigures brainwide network dynamics toward salience-related statesPreprint
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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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