Article | Published:

Oxytocin enables maternal behaviour by balancing cortical inhibition

Nature volume 520, pages 499504 (23 April 2015) | Download Citation

Abstract

Oxytocin is important for social interactions and maternal behaviour. However, little is known about when, where and how oxytocin modulates neural circuits to improve social cognition. Here we show how oxytocin enables pup retrieval behaviour in female mice by enhancing auditory cortical pup call responses. Retrieval behaviour required the left but not right auditory cortex, was accelerated by oxytocin in the left auditory cortex, and oxytocin receptors were preferentially expressed in the left auditory cortex. Neural responses to pup calls were lateralized, with co-tuned and temporally precise excitatory and inhibitory responses in the left cortex of maternal but not pup-naive adults. Finally, pairing calls with oxytocin enhanced responses by balancing the magnitude and timing of inhibition with excitation. Our results describe fundamental synaptic mechanisms by which oxytocin increases the salience of acoustic social stimuli. Furthermore, oxytocin-induced plasticity provides a biological basis for lateralization of auditory cortical processing.

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Acknowledgements

We thank V. Azzara, R. Alicka, H. Bernstein, G. Buzsaki, I. Carcea, C. Grosso, M. Insanally, M. Jin, K. Kuchibhotla, B. Y. B. Lau, D. Lin, M. A. Long, N. Lopez, J. Marlin, C. McFarlane, E. Morina, S. Norden, D. Okobi, K. Peng, R. Priya, W. Rashid, L. Rubin, S. Shea, R. M. Sullivan, R. W. Tsien, D. Vallentin, L. J. Young and N. Zaika for comments, discussions and technical assistance, A. Mar and the NYU School of Medicine Behavioral Core for assistance with behavioural analysis, and C. A. Loomis and the NYU School of Medicine Histology Core for assistance with anatomical studies. Oxytocin-IRES-Cre mice were obtained from D. Olson and B. Lowell. Oxytocin receptor knockout mice were obtained from R. W. Tsien. Oxytocin receptor plasmid (pAAV-OXTR) was obtained from L. J. Young. Adeno-associated virus was obtained from the U. Penn Vector Core. S. E. Ross created artwork in Fig. 1a. This work was funded by NIDCD (DC009635, DC12557), a Klingenstein Fellowship, a McKnight Scholarship, a Pew Scholarship, a Sloan Research Fellowship, and a Whitehead Foundation Fellowship (R.C.F.); a Skirball Institute Collaborative Research Award (M.V.C. and R.C.F.); and NIMH (T32; B.J.M.).

Author information

Affiliations

  1. Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA

    • Bianca J. Marlin
    • , Mariela Mitre
    • , James A. D’amour
    • , Moses V. Chao
    •  & Robert C. Froemke
  2. Neuroscience Institute, New York University School of Medicine, New York, New York 10016, USA

    • Bianca J. Marlin
    • , Mariela Mitre
    • , James A. D’amour
    • , Moses V. Chao
    •  & Robert C. Froemke
  3. Department of Otolaryngology, New York University School of Medicine, New York, New York 10016, USA

    • Bianca J. Marlin
    • , Mariela Mitre
    • , James A. D’amour
    •  & Robert C. Froemke
  4. Department of Neuroscience and Physiology, New York University School of Medicine, New York, New York 10016, USA

    • Bianca J. Marlin
    • , Mariela Mitre
    • , James A. D’amour
    • , Moses V. Chao
    •  & Robert C. Froemke
  5. Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA

    • Mariela Mitre
    •  & Moses V. Chao
  6. Department of Psychiatry, New York University School of Medicine, New York, New York 10016, USA

    • Mariela Mitre
    •  & Moses V. Chao
  7. Center for Neural Science, New York University, New York, New York 10003, USA

    • Moses V. Chao
    •  & Robert C. Froemke

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Contributions

B.J.M. conducted behavioural studies and in vivo recordings. M.M. conducted anatomical studies. J.A.D. conducted in vitro recordings. M.M. and M.V.C. generated OXTR-2. R.C.F. and B.J.M. designed the study. All authors analysed data and wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Robert C. Froemke.

Extended data

Supplementary information

Videos

  1. 1.

    Pup retrieval by experienced mother

    This video shows pup retrieval by an experienced mother.

  2. 2.

    No retrieval by saline-injected virgin female

    This video shows no retrieval by saline-injected virgin female.

  3. 3.

    Pup retrieval by Oxt-IRES-Cre virgin female after PVN optical stimulation

    This video shows pup retrieval by Oxt-IRES-Cre virgin female after PVN optical stimulation.

  4. 4.

    Muscimol in left auditory cortex prevents pup retrieval

    This video shows muscimol in left auditory cortex prevents pup retrieval.

  5. 5.

    Pup retrieval by wild-type virgin female after left AI oxytocin infusion

    This video shows pup retrieval by wild-type virgin female after left AI oxytocin infusion.

  6. 6.

    Pup retrieval by Oxt-IRES-Cre virgin female after left AI optical stimulation

    This video shows pup retrieval by Oxt-IRES-Cre virgin female after left AI optical stimulation.

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DOI

https://doi.org/10.1038/nature14402

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