Bidirectional control of infant rat social behavior via dopaminergic innervation of the basolateral amygdala

Maya Opendak; Charlis Raineki; Rosemarie E Perry; Millie Rincón-Cortés; Soomin C Song; Roseanna M Zanca; Emma Wood; Katherine Packard; Shannon Hu; Joyce Woo; Krissian Martinez; K Yaragudri Vinod; Russell W Brown; Gerald A Deehan Jr; Robert C Froemke; Peter A Serrano; Donald A Wilson; Regina M Sullivan

doi:10.1016/j.neuron.2021.09.041

Bidirectional control of infant rat social behavior via dopaminergic innervation of the basolateral amygdala

Neuron. 2021 Dec 15;109(24):4018-4035.e7. doi: 10.1016/j.neuron.2021.09.041. Epub 2021 Oct 26.

Authors

Maya Opendak¹, Charlis Raineki², Rosemarie E Perry³, Millie Rincón-Cortés⁴, Soomin C Song⁵, Roseanna M Zanca⁶, Emma Wood⁷, Katherine Packard⁷, Shannon Hu⁷, Joyce Woo⁷, Krissian Martinez⁸, K Yaragudri Vinod⁹, Russell W Brown¹⁰, Gerald A Deehan Jr¹¹, Robert C Froemke¹², Peter A Serrano¹³, Donald A Wilson¹⁴, Regina M Sullivan¹⁵

Affiliations

¹ Department of Child and Adolescent Psychiatry, NYU Langone Health, New York, NY 10016, USA; Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Kennedy Krieger Institute, Baltimore, MD 21205, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: opendak@kennedykrieger.org.
² Department of Child and Adolescent Psychiatry, NYU Langone Health, New York, NY 10016, USA; Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Department of Psychology, Brock University, St. Catharines, ON L2S 3A1, Canada.
³ Department of Child and Adolescent Psychiatry, NYU Langone Health, New York, NY 10016, USA; Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Department of Applied Psychology, New York University, New York, NY 10012, USA.
⁴ Department of Child and Adolescent Psychiatry, NYU Langone Health, New York, NY 10016, USA; Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Department of Neuroscience, University of Pittsburgh, Pittsburgh PA 15260, USA.
⁵ Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA; Neuroscience Institute, New York University School of Medicine, New York, NY 10016, USA.
⁶ Department of Child and Adolescent Psychiatry, NYU Langone Health, New York, NY 10016, USA; Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Department of Psychology, CUNY Hunter College, New York, 10016, USA; The Graduate Center of CUNY, New York, 10016, USA.
⁷ Department of Child and Adolescent Psychiatry, NYU Langone Health, New York, NY 10016, USA; Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
⁸ Department of Child and Adolescent Psychiatry, NYU Langone Health, New York, NY 10016, USA.
⁹ Department of Child and Adolescent Psychiatry, NYU Langone Health, New York, NY 10016, USA; Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
¹⁰ Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
¹¹ Department of Psychology, East Tennessee State University, Johnson City, TN 37614, USA.
¹² Center for Neural Science, New York University, New York, NY 10003, USA; Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA; Neuroscience Institute, New York University School of Medicine, New York, NY 10016, USA; Department of Otolaryngology, New York University School of Medicine, New York, NY 10016, USA; Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016, USA.
¹³ Department of Psychology, CUNY Hunter College, New York, 10016, USA; The Graduate Center of CUNY, New York, 10016, USA.
¹⁴ Department of Child and Adolescent Psychiatry, NYU Langone Health, New York, NY 10016, USA; Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Center for Neural Science, New York University, New York, NY 10003, USA.
¹⁵ Department of Child and Adolescent Psychiatry, NYU Langone Health, New York, NY 10016, USA; Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Center for Neural Science, New York University, New York, NY 10003, USA. Electronic address: regina.sullivan@nyulangone.org.

Abstract

Social interaction deficits seen in psychiatric disorders emerge in early-life and are most closely linked to aberrant neural circuit function. Due to technical limitations, we have limited understanding of how typical versus pathological social behavior circuits develop. Using a suite of invasive procedures in awake, behaving infant rats, including optogenetics, microdialysis, and microinfusions, we dissected the circuits controlling the gradual increase in social behavior deficits following two complementary procedures-naturalistic harsh maternal care and repeated shock alone or with an anesthetized mother. Whether the mother was the source of the adversity (naturalistic Scarcity-Adversity) or merely present during the adversity (repeated shock with mom), both conditions elevated basolateral amygdala (BLA) dopamine, which was necessary and sufficient in initiating social behavior pathology. This did not occur when pups experienced adversity alone. These data highlight the unique impact of social adversity as causal in producing mesolimbic dopamine circuit dysfunction and aberrant social behavior.

Keywords: adversity; amygdala; development; dopamine; parenting; social behavior.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amygdala
Animals
Basolateral Nuclear Complex*
Dopamine*
Humans
Optogenetics
Rats
Social Behavior

Substances

Dopamine

Abstract

Publication types

MeSH terms

Substances

Grants and funding