Developmental Effects of Oxytocin Neurons on Social Affiliation and Processing of Social Information
- Ana Rita Nunes1,2,*,
- Michael Gliksberg2,*,
- Susana A. M. Varela1,3,
- Magda Teles1,
- Einav Wircer2,
- Janna Blechman2,
- Giovanni Petri4,
- Gil Levkowitz2,5, and
- Rui F. Oliveira1,3,6
- 1Integrative Behavioural Biology Lab, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal
- 2Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel
- 3ISPA-Instituto Universitário, Lisboa 1149-041, Portugal
- 4Institute for Scientific Interchange (ISI) Foundation and ISI Global Science Foundation, Torino 10126, Italy
- 5Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot 7610001, Israel
- 6Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon 1400-038, Portugal
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Author contributions: A.R.N., M.G., S.A.M.V., M.T., G.P., G.L., and R.F.O. designed research; A.R.N., M.G., S.A.M.V., and M.T. performed research; E.W., J.B., G.L., and R.F.O. contributed unpublished reagents/analytic tools; A.R.N., M.G., S.A.M.V., M.T., E.W., J.B., and G.P. analyzed data; A.R.N., M.G., S.A.M.V., M.T., G.P., and R.F.O. wrote the first draft of the paper; A.R.N., M.G., S.A.M.V., M.T., G.P., G.L., and R.F.O. edited the paper; A.R.N., M.G., S.A.M.V., M.T., G.P., G.L., and R.F.O. wrote the paper.
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↵*A.R.N. and M.G. contributed equally to this work.
Abstract
Hormones regulate behavior either through activational effects that facilitate the acute expression of specific behaviors or through organizational effects that shape the development of the nervous system thereby altering adult behavior. Much research has implicated the neuropeptide oxytocin (OXT) in acute modulation of various aspects of social behaviors across vertebrate species, and OXT signaling is associated with the developmental social deficits observed in autism spectrum disorders (ASDs); however, little is known about the role of OXT in the neurodevelopment of the social brain. We show that perturbation of OXT neurons during early zebrafish development led to a loss of dopaminergic neurons, associated with visual processing and reward, and blunted the neuronal response to social stimuli in the adult brain. Ultimately, adult fish whose OXT neurons were ablated in early life, displayed altered functional connectivity within social decision-making brain nuclei both in naive state and in response to social stimulus and became less social. We propose that OXT neurons have an organizational role, namely, to shape forebrain neuroarchitecture during development and to acquire an affiliative response toward conspecifics.
SIGNIFICANCE STATEMENT Social behavior is developed over the lifetime of an organism and the neuropeptide oxytocin (OXT) modulates social behaviors across vertebrate species, and is associated with neuro-developmental social deficits such as autism. However, whether OXT plays a role in the developmental maturation of neural systems that are necessary for social behavior remains poorly explored. We show that proper behavioral and neural response to social stimuli depends on a developmental process orchestrated by OXT neurons. Animals whose OXT system is ablated in early life show blunted neuronal and behavioral responses to social stimuli as well as wide ranging disruptions in the functional connectivity of the social brain. We provide a window into the mechanisms underlying OXT-dependent developmental processes that implement adult sociality.
- Received November 19, 2020.
- Revision received June 23, 2021.
- Accepted June 28, 2021.
- Copyright © 2021 the authors
