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Neural circuitry for maternal oxytocin release induced by infant cries

Nature volume 621, pages 788–795 (2023)Cite this article

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Abstract

Oxytocin is a neuropeptide that is important for maternal physiology and childcare, including parturition and milk ejection during nursing1,2,3,4,5,6. Suckling triggers the release of oxytocin, but other sensory cues—specifically, infant cries—can increase the levels of oxytocin in new human mothers7, which indicates that cries can activate hypothalamic oxytocin neurons. Here we describe a neural circuit that routes auditory information about infant vocalizations to mouse oxytocin neurons. We performed in vivo electrophysiological recordings and photometry from identified oxytocin neurons in awake maternal mice that were presented with pup calls. We found that oxytocin neurons responded to pup vocalizations, but not to pure tones, through input from the posterior intralaminar thalamus, and that repetitive thalamic stimulation induced lasting disinhibition of oxytocin neurons. This circuit gates central oxytocin release and maternal behaviour in response to calls, providing a mechanism for the integration of sensory cues from the offspring in maternal endocrine networks to ensure modulation of brain state for efficient parenting.

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Fig. 1: Delayed persistent activation of dam oxytocin neurons by pup vocalizations.
Fig. 2: PVN oxytocin neurons receive projections from the auditory thalamus.
Fig. 3: Activation of PIL–PVN inputs decreases inhibition in oxytocin neurons through postsynaptic NMDARs and the dynamin-dependent internalization of GABAARs.
Fig. 4: Chemogenetic inhibition of PIL projections to PVN impairs the detection of pup calls and pup-retrieval behaviour.
Fig. 5: Pup calls trigger the release of oxytocin in the VTA through the PIL-to-PVN pathway.

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Data availability

Fibre photometry data are available on Zenodo: https://doi.org/10.5281/zenodo.8060338. Any updates to the above will be reflected in the NYU Data Catalog at https://datacatalog.med.nyu.edu/dataset/10623. Requests for further information about resources and reagents used and requests for data should be directed to and will be fulfilled by S.V. and R.C.F.

Code availability

Scripts used to analyse fibre photometry are available on GitHub: https://github.com/valtchevas/valtcheva_et_al_2023.

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Acknowledgements

We thank I. Carcea, E. Glennon, K. V. Kuchibhotla, J. K. Schiavo and S. C. Song for comments, discussions and technical assistance; the NYU Langone Microscopy Core for experimental and technical support; D. Rinberg for sharing the custom-made 3D-printed headpost and head-fixation frame design; and D. Lin for help with the code for analysing the fibre photometry data. Initial aliquots of the EnvA G-Deleted Rabies-mCherry (SADΔG-mCherry) and helper AAV2-EF1a-FLEX-TVA-GFP viruses were a gift from G. Fishell. Illustrations in Figs. 1a,j and 5d,i and Extended Data Figs. 4a, 6a and 10b were made by S. E. Ross. This work was funded by a Fyssen Foundation Postdoctoral Fellowship, a Leon Levy Foundation Postdoctoral Fellowship and a Brain & Behavior Research Foundation NARSAD Young Investigator Award (S.V.); a T32 MH019524 Training in Systems and Integrative Neuroscience award (H.A.I.); a Natural Sciences and Engineering Research Council of Canada PGS-D fellowship (C.J.B.-M.); an NSF Graduate Research Fellowship (K.A.M.); DP1MH119428 (H.-B.K.); the BRAIN Initiative (NS107616; Y.Z. and R.C.F.); and NINDS (NS074972), NICHD (HD088411), NIDCD (DC12557) and a Howard Hughes Medical Institute Faculty Scholarship (R.C.F.).

Author information

Author notes

  1. These authors contributed equally: Silvana Valtcheva, Habon A. Issa

Authors and Affiliations

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

    Silvana Valtcheva, Habon A. Issa, Chloe J. Bair-Marshall, Kathleen A. Martin & Robert C. Froemke

  2. Neuroscience Institute, New York University School of Medicine, New York, NY, USA

    Silvana Valtcheva, Habon A. Issa, Chloe J. Bair-Marshall, Kathleen A. Martin, Yiyao Zhang & Robert C. Froemke

  3. Department of Otolaryngology, New York University School of Medicine, New York, NY, USA

    Silvana Valtcheva, Habon A. Issa, Chloe J. Bair-Marshall, Kathleen A. Martin & Robert C. Froemke

  4. Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY, USA

    Silvana Valtcheva, Habon A. Issa, Chloe J. Bair-Marshall, Kathleen A. Martin & Robert C. Froemke

  5. Center for Neural Science, New York University, New York, NY, USA

    Silvana Valtcheva, Habon A. Issa, Chloe J. Bair-Marshall, Kathleen A. Martin & Robert C. Froemke

  6. Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Kanghoon Jung & Hyung-Bae Kwon

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Contributions

S.V. performed in vivo cell-attached, whole-cell and tungsten recordings, fibre photometry, in vitro whole-cell recordings, behaviour for chemogenetic inactivation studies, oxytocin sensor experiments, viral injections, histology, image acquisition and data analysis of electrophysiology and behaviour experiments. H.A.I. performed fibre photometry and behaviour for chemogenetic inactivation and cannula infusion studies. C.J.B.-M. performed fibre photometry and in vitro whole-cell recordings for the scrambled dynamin inhibitor experiments. H.A.I., K.A.M. and Y.Z. wrote code and performed analysis of the photometry recordings. K.J. and H.-B.K. contributed to the design of viral constructs and data analysis for the oxytocin sensor. S.V. and R.C.F. designed the study and wrote the paper.

Corresponding authors

Correspondence to Silvana Valtcheva or Robert C. Froemke.

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Extended data figures and tables

Extended Data Fig. 1 Identification of ChR2+ (OT+) and ChR2− (OT−) neurons.

a, Sample traces and raster plots of cell-attached recordings from one ChR2+ (OT+, left) and one ChR2− (OT−, right) neuron showing reliable activation of ChR2+ (OT+) neurons in response to 50 ms pulses of blue light at 5 Hz (20–100% laser power). b, Increase in the number of spikes (left) of ChR2+ (OT+; pink circles; n = 7 neurons, N = 5 dams, p = 0.002, one-way ANOVA) and spike probability (right; p = 0.009) in response to 50 ms light pulse steps. Number of spikes of ChR2− (OT−; black circles; n = 13, N = 3, p = 0.11) neurons, as well as spike probability (p = 0.13) was not modulated. c, Sample traces and raster plots of cell-attached recordings of one ChR2+ (OT+, left) and one ChR2− (OT−, right). ChR2+ (OT+) neuron was reliably activated in response to 200-ms pulses of blue light (0–100% laser power). d, Increase in the number of spikes (left) of ChR2+ (OT+; pink circles; n = 9 neurons, N = 6 dams, p = 0.002, one-way ANOVA) and spike probability (right; p = 0.01) in response to 200 ms light pulse steps. Number of spikes of ChR2− (OT−; black circles; n = 13, N = 3, p = 0.49) neurons, as well as spike probability (p = 0.62) was not modulated. e, Increase in firing rate of ChR2+ (OT+; n = 10 neurons, N = 5 dams, p = 0.0001, one-way ANOVA) but not of ChR2− (OT−; n = 13, N = 3, p = 0.68) neurons in response to 200 ms light pulse of 100% laser power (‘Opto’) compared to their baseline firing rate immediately preceding (‘Pre’) and immediately after (‘Post’) the light pulse. f, Change of firing rate of ChR2+ (OT+; n = 10 neurons, N = 5 dams, p = 0.002, Wilcoxon matched-pairs signed-rank two-tailed test) but not of ChR2− (OT−; n = 13, N = 3, p = 0.91) neurons in response to 200-ms light pulse of 100% laser power (‘Opto’) compared to baseline firing immediately preceding the light pulse (‘Pre’). g, Box plots (showing the median (line), second to third quartiles (box), minimum to maximum (whiskers) of latency to first spike was significantly shorter in ChR2+ (OT+; n = 14 neurons, N = 6 dams, p < 0.0001, Mann–Whitney two-tailed test) compared to ChR2− (OT−; n = 8, N = 2) neurons in response to 200-ms light pulse of 100% laser power. ‘First spike’ in ChR2− (OT−) cells was not light-evoked but occurred spontaneously. Data reported as mean ± s.e.m. *P < 0.05. **P < 0.01.

Source data

Extended Data Fig. 2 In vivo responses to individual pup calls.

a, Location and firing rate of cell-attached (n = 19 neurons, N = 8 dams) and whole-cell (n = 1) recordings of ChR2+ OT+ neurons and ChR2− neurons (OT−, cell-attached: n = 16 neurons, N = 8 dams; whole-cell: n = 2, N = 2). b, Sample traces of whole-cell recordings of one ChR2+ (OT+; upper trace) and one ChR2− (OT−; lower trace) neuron during call playback (‘Calls’). Pink bars, individual pup calls. c, Left, Cell-attached recording of one ChR2+ (OT+) neuron before pup-call onset (1, ‘Pre’), and around 2 min after call onset (2, ‘Post’). Right, Peristimulus time histogram. Bins: 20 s. d, Timeline of ChR2+ (OT+; n = 12 neurons) and ChR2− (OT−; n = 11) responses. Period before (1, ‘Pre’) and after (2, ‘Post’) pup-call onset. e,f, Sample traces of whole-cell recordings of one ChR2+ (OT+; e) and one ChR2− (OT−; f) neuron showing baseline spiking activity preceding onset of pup calls (1, ‘Pre’, upper trace), activity during playback of a set of pup calls (‘Calls’, middle trace) and activity after pup calls playback (2, ‘Post’, lower trace). Note increased firing rate for ChR2+ (OT+) neuron but not ChR2− (OT−) neuron. g, ChR2+ (OT+) did not respond to individual pup calls within a set. ‘Pre’, average spiking rate of cell-attached recordings during all baseline periods immediately preceding each call within the set. ‘Call’, average spiking rate during pup-call stimulus for each call within the set. Neither ChR2+ (OT+; n = 9 neurons, N = 6 dams, p = 0.38, Wilcoxon matched-pairs signed-rank two-tailed test), nor ChR2− (OT−; n = 9, N = 5, p = 0.30) neurons increased their firing rate during individual calls (‘Call’) compared to baseline (‘Pre’). h–j, ChR2+ (OT+) did not respond to presentation of individual pup calls on a trial-by-trial basis. h, Sample traces of cell-attached recordings of one ChR2+ (OT+), one ChR2− (OT−) and one unidentified PVN neuron, as well as whole-cell recording of a PVN neuron during trial-by-trial individual pup-call presentation. i, No increase in the firing rates of either ChR2+ (OT+; n = 8 neurons, N = 2 dams, p = 0.38, Wilcoxon matched-pairs signed-rank two-tailed test), ChR2− (OT−; n = 7, N = 3, p = 0.08), or unidentified PVN (cell-attached: n = 26, N = 13; whole-cell: n = 6, N = 4, p = 0.48) neurons during individual pup calls (‘Call’) compared to baseline (‘Pre’) on a trial-by-trial basis. j, No difference in the z-scores of spiking responses of cell-attached and whole-cell recordings during individual pup calls in ChR2+ (OT+; n = 8, N = 2, p = 0.30, one-way ANOVA), ChR2− (OT−; n = 7, N = 4), and unidentified PVN (cell-attached: n = 21, N = 11; whole-cell: n = 6, N = 4) neurons. Data reported as mean ± s.e.m. *P < 0.05.

Source data

Extended Data Fig. 3 In vivo responses to auditory stimuli.

a–h, Z-scores of fluorescence activity during fibre photometry recordings of dams and virgins in response to auditory stimuli. Pup calls trigger sustained increase in the activity of oxytocin neurons in dams (a; N = 7; Pre vs Post: p = 0.018; Wilcoxon matched-pairs signed-rank one-tailed test) but not virgins (b; N = 4; p = 0.50; Wilcoxon matched-pairs signed-rank one-tailed test). No responses to adult calls (c; N = 4 dams; p = 0.5966; and d; N = 3 virgins; p = 0.09; Wilcoxon matched-pairs signed-rank one-tailed test) or ultrasound pure tones (e; N = 3 dams; p = 0.38; and f; N = 3 virgins; p = 0.47; Wilcoxon matched-pairs signed-rank one-tailed test). No response to pure tones (g; N = 3; p = 0.11; Wilcoxon matched-pairs signed-rank one-tailed test) or FM sweeps (h; N = 5; p = 0.20; Wilcoxon matched-pairs signed-rank one-tailed test) in dams. Insets represent fluorescence activity during a single trial from two different mice per condition. i, Responses to pup calls across dams and trials (pup calls, dam: n = 28 trials; adult calls, dam: n = 16; FM sweeps, dam: n = 19; tones, dam: n = 12; ultrasound, dam: n = 12; pup calls, virgin: n = 16). j, Average z-score responses to auditory stimuli for individual trials. k, PVN neurons did not respond to individual pure tones. Left, example cell-attached recording of one PVN neuron in response to 23 kHz tone presentation and tuning profile of pure-tone frequency responses in this cell. Right, average tuning profile of pure-tone frequency responses in PVN cells (n = 15 neurons, N = 9 dams). Data reported as median ± 95% CI (j) or as median or mean ± s.e.m. (k). *P < 0.05.

Source data

Extended Data Fig. 4 Auditory responses in the PIL.

a, Left, experimental set-up showing in vivo multiunit recordings via tungsten electrode in the PIL of awake head-fixed wild-type dams while playing pup calls from an ultrasound speaker. Right, validation of PIL recording site by coating tungsten electrode tip with DiI. Scale, 500 µm. MGB, medial geniculate body of the thalamus; PIL, posterior intralaminar nucleus of the thalamus; SN, substantia nigra. b–g, In vivo activation of PIL during playback of pup calls and pure tones. Sample trace of stimulus-evoked PIL multiunit spiking activity during individual pup call (b) and 23 kHz tone (c) presentation. Note the increase in PIL activity during the entire duration of the pup call (>1 s) compared to transient activation during pure tones. Pup calls increased the firing frequency of PIL neurons (d; N = 6 dams, p = 0.03, Wilcoxon matched-pairs signed-rank two-tailed test) which corresponded to a significant increase from baseline values (e; N = 6 dams; p = 0.02, one-sample two-tailed Student’s t-test). f, There was no difference in the frequency of multiunit spiking during pup calls and pure tones playback (N = 6 dams; p = 0.33, Mann–Whitney two-tailed test). g, Tuning profile of pure-tone frequency responses in PIL (N = 5 dams). Data reported as mean ± s.e.m. *P < 0.05; ns, not significant.

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Extended Data Fig. 5 Auditory projections to the PVN.

a, Schematic showing injection of AAV1-hSyn-hChR2(H134R)-EYFP in the PIL of Oxytocin:Cre × Ai9 dams prior to whole-cell recordings from oxytocin neurons (tdTomato+) in PVN brain slices. PIL, posterior intralaminar nucleus of the thalamus; PVN, paraventricular nucleus of the hypothalamus. b,c, PVN oxytocin neurons receive mainly glutamatergic input from the PIL. Percentage of optogenetically evoked excitatory (oEPSCs) and inhibitory (oIPSCs) currents in oxytocin neurons triggered by optogenetic stimulation of PIL axons (b) and characterization of oIPSCs (c; n = 12 neurons). d,e, PIL inputs to oxytocin cells are monosynaptic. d, Example traces and summary graph showing oEPSCs in the presence of TTX and 4-AP and their inhibition by DNQX (n = 8 neurons, p = 0.016, Wilcoxon matched-pairs signed-rank test). e, Example traces and summary graph showing oIPSCs in the presence of TTX and 4-AP; DNQX had no effect on oIPSCs amplitude (n = 5 neurons, p = 0.63, Wilcoxon). f–h, Parvocellular PVN oxytocin neurons are the main target of input from the PIL. Magnocellular (MagnOT) and parvocellular (ParvOT) oxytocin neurons were characterized by their signature spiking patterns in current-clamp mode (f; left). 5/16 MagnOT and 11/16 ParvOT cells received inputs from the PIL (f; right). g,h, Characterization of oEPSCs in MagnOT and ParvOT neurons triggered by optogenetic stimulation of PIL axons. g, Example traces from one magnocellular (left) and one parvocellular (right) oxytocin cell. There was no difference in oEPSCs amplitude (h, left; MagnOT: n = 5 neurons, ParvOT: n = 11; p = 0.51, Mann–Whitney two-tailed test) but the latency of oEPSCs in ParvOT cells was longer (h, right; MagnOT: n = 5 neurons, ParvOT: n = 11; p = 0.0275, Mann–Whitney two-tailed test). i, The PVN does not receive input from IC. Left, injection of AAV1-hSyn-hChR2(H134R)-EYFP in IC of wild-type dams. Right, no EYFP staining was found in PVN, suggesting that IC does not project to PVN. Scale, 200 µm. N = 3. IC, inferior colliculus. j, The PVN does not receive input from AuCx. Left, injection of AAV1-hSyn-hChR2(H134R)-EYFP in AuCx of wild-type dams. Right, no EYFP staining was found in PVN, suggesting that AuCx does not project to PVN. Scale, 200 µm. N = 2. AuCx, auditory cortex. Data reported as mean ± s.e.m. *P < 0.05.

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Extended Data Fig. 6 PIL neurons do not exhibit sustained increases in firing after pup calls in vivo.

a, Experimental set-up showing in vivo cell-attached recordings in PIL of awake wild-type dams while playing pup calls from an ultrasound speaker. PIL, posterior intralaminar nucleus of the thalamus. b, Location (depth from pia) and firing rate of PIL neurons (n = 9 neurons; N = 4 dams). c–e, PIL neurons did not modulate their firing rate following playback of a set of pup calls (15 pup calls, 1 s gap in between calls). c, Sample traces from a cell-attached recording of one PIL neuron showing its baseline firing rate immediately preceding (1, ‘Pre’) and at 90 s after the onset of pup calls playback (2, ‘Post’). Firing rates during baseline and after pup calls were calculated over 1–2 min. d, Timeline of responses of PIL neurons. e, PIL neurons (n = 9) did not exhibit persistent increases in baseline firing following pup calls, as calculated between 80–160 s after onset of pup-call playback (e, n = 9 neurons, N = 4 dams, p = 0.77, one-sample two-tailed Student’s t-test). Data reported as mean ± s.e.m.; ns, not significant.

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Extended Data Fig. 7 PIL inputs to the PVN do not induce postsynaptic spiking or affect the excitability of oxytocin neurons.

a, Schematic showing injection of AAV1-hSyn-hChR2(H134R)-EYFP in PIL of Oxytocin:Cre × Ai9 dams before whole-cell recordings from oxytocin neurons (tdTomato+) in PVN brain slices. PIL, posterior intralaminar nucleus of the thalamus; PVN, paraventricular nucleus of the hypothalamus. b, Whole-cell recordings from tdTomato+ oxytocin neurons in PVN slices, optogenetic stimulation of PIL axons and placement of the extracellular stimulation electrode. c,d, Optogenetic stimulation of PIL axons in PVN does not induce postsynaptic spiking in oxytocin neurons. c, Single pulse of optogenetic stimulation triggered postsynaptic potentials but did not induce spiking in oxytocin cells (n = 8 neurons). d, Repeated optogenetic stimulation of PIL axons (‘PIL opto’) did not trigger depolarization of oxytocin cells (n = 16 neurons; p = 0.10, Wilcoxon matched-pairs signed-rank two-tailed test) and did not induce postsynaptic spiking (n = 16 neurons; p = 0.26, Wilcoxon matched-pairs signed-rank two-tailed test). e,f, No change in the number of spikes in oxytocin neurons in response to 20 pA steps of intracellular current injection before (‘Pre’) or after (‘Post’) PIL opto. Sample traces (e) and summary (f; n = 9 neurons, p > 0.44, Wilcoxon matched-pairs signed-rank two-tailed test). g–i, No change in the intrinsic properties of oxytocin neurons after PIL opto, in terms of rheobase (g; n = 9 neurons; p = 0.38, Wilcoxon matched-pairs signed-rank two-tailed test), resting membrane potential (h; n = 6 neurons; p = 0.16, Wilcoxon matched-pairs signed-rank two-tailed test), or input resistance (i; n = 12 neurons; p = 0.06, Wilcoxon matched-pairs signed-rank two-tailed test). Data reported as mean ± s.e.m.

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Extended Data Fig. 8 Prolonged but not brief optogenetic stimulation of PIL axons triggers iLTD.

a, Whole-cell recordings from tdTomato+ oxytocin neurons in PVN slices, optogenetic stimulation of PIL axons and placement of the extracellular stimulation electrode. b, Whole-cell voltage-clamp recordings showing that the amplitude of oEPSCs triggered by single pulse of optogenetic stimulation was not modified following repeated optogenetic stimulation of PIL axons (‘PIL opto’; n = 6 neurons, p = 0.13, one-sample two-tailed Student’s t-test). c, IPSC/EPSC ratio decreased following PIL opto (n = 6 neurons; p = 0.0018, one-sample two-tailed Student’s t-test). d–f, Repeated but brief optogenetic stimulation of PIL axons (‘PIL opto short’) did not induce iLTD: example cell (d; p = 0.74, Mann–Whitney two-tailed test) and summary (e; n = 6 neurons, p = 0.99, one-sample two-tailed Student’s t-test). f, No change in IPSC/EPSC ratio following PIL opto short (n = 6 neurons; p = 0.49, one-sample two-tailed Student’s t-test). g–i, In vivo exposed to pup calls playback occlude iLTD. g,h, Schematic of experimental protocol (g): example cell (g; p = 0.94, Mann–Whitney two-tailed test) and summary (h; n = 4 neurons, p = 0.98, one-sample two-tailed Student’s t-test). i, No change in IPSC/EPSC ratio following PIL opto in slices of dams exposed to pup calls in vivo (n = 4 neurons; p = 0.76, one-sample two-tailed Student’s t-test). Data reported as mean ± s.d. **P < 0.01; ns, not significant.

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Extended Data Fig. 9 iLTD in oxytocin neurons relies on postsynaptic NMDARs and dynamin signalling.

a, Whole-cell voltage-clamp recordings showing intact iLTD after repeated optogenetic stimulation of PIL terminals in PVN (‘PIL opto’) in presence of bath-applied type-III mGluR antagonist MAP4 (250 µM), for example neuron (top; p < 0.0001, Mann–Whitney two-tailed test) and summary (middle; n = 5 neurons, p = 0.02, one-sample two-tailed Student’s t-test). Bottom, IPSC/EPSC ratio in the presence of MAP4. b, iLTD in oxytocin neurons is NMDAR-dependent. Whole-cell voltage-clamp recordings showing no plasticity after PIL opto in presence of bath-applied AP5 (50 µM), for example neuron (top; p = 0.62, Mann–Whitney two-tailed test) and summary (middle; n = 8 neurons, p = 0.44, one-sample two-tailed Student’s t-test). Bottom, unchanged IPSC/EPSC ratio in the presence of AP5. c, iLTD in oxytocin neurons is dependent on postsynaptic NMDARs. Whole-cell voltage-clamp recordings showing no plasticity after PIL opto when i-MK801 (1 mM) was applied in the recording pipette, for example neuron (top; p = 0.11, Mann–Whitney two-tailed test) and summary (middle; n = 6 neurons, p = 0.18, one-sample two-tailed Student’s t-test). Bottom, unchanged IPSC/EPSC ratio in the presence of i-MK801. d, Whole-cell voltage-clamp recordings showing intact iLTD after PIL opto in presence of bath-applied OXTR antagonist OTA (1 µM), for example neuron (top; p < 0.0001, Mann–Whitney two-tailed test) and summary (middle; n = 8 neurons, p = 0.0008, one-sample two-tailed Student’s t-test). Bottom, IPSC/EPSC ratio in the presence of OTA. e,f, iLTD in oxytocin neurons is dependent on dynamin signalling. e, Whole-cell voltage-clamp recordings showing no plasticity after PIL opto when i-Dynamin inhibitor (1.5 mM) was applied in the recording pipette, for example neuron (top; p = 0.30, Mann–Whitney two-tailed test) and summary (middle; n = 7 neurons, p = 0.63, one-sample two-tailed Student’s t-test). Bottom, unchanged IPSC/EPSC ratio in the presence of i-Dynamin inhibitor. f, Whole-cell voltage-clamp recordings showing intact iLTD in oxytocin cells in the presence of a scrambled dynamin inhibitor in the recording pipette, for example neuron (top; p < 0.0001, Mann–Whitney two-tailed test) and summary (middle; n = 8 neurons, p = 0.0096, one-sample two-tailed Student’s t-test). Bottom, IPSC/EPSC ratio in the presence of a scrambled dynamin inhibitor. Data reported as mean ± s.d. *P < 0.05, **P < 0.01; ns, not significant.

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Extended Data Fig. 10 Inhibiting oxytocin signalling in the VTA impairs pup-retrieval behaviour.

a, Pup-retrieval protocol. b,c, Wild-type dams infused with the OXTR antagonist OTA (0.5 mg ml−1; b) retrieved less pups compared to saline controls (c; N = 4 dams, P at least <0.02, two-tailed Fisher’s test). Data reported as mean ± s.e.m. *P < 0.05.

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Valtcheva, S., Issa, H.A., Bair-Marshall, C.J. et al. Neural circuitry for maternal oxytocin release induced by infant cries. Nature 621, 788–795 (2023). https://doi.org/10.1038/s41586-023-06540-4

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