Resource Scarcity But Not Maternal Separation Provokes Unpredictable Maternal Care Sequences in Mice and Both Upregulate Crh-Associated Gene Expression in the Amygdala

23 Pages Posted: 9 Jul 2022

See all articles by Camila Demaestri

Camila Demaestri

Columbia University

Meghan E. Gallo

Brown University

Elisa Mazenod

Brown University - Department of Cognitive, Linguistic and Psychological Sciences

Alexander T. Hong

University of California, Irvine

Hina Arora

University of California, Irvine

Annabel K. Short

University of California, Irvine

Hal S. Stern

University of California, Irvine - Department of Statistics

Tallie Z. Baram

University of California, Irvine, School of Medicine, Department of Pediatrics; University of California, Irvine, School of Medicine, Department of Anatomy/Neurobiology; University of California, Irvine - Department of Neurology

Kevin G. Bath

Columbia University

Abstract

Early life adversity (ELA) is a major risk factor for the development of pathology, including anxiety disorders. Neurodevelopmental and behavioral outcomes following ELA are multifaceted and are influenced heavily by the type of adversity experienced and sex of the individual experiencing ELA. It remains unclear what properties of ELA portend differential neurobiological risk and the basis of sex-differences for negative outcomes. Predictability of the postnatal environment has emerged as being a core feature supporting development, with the most salient signals deriving from parental care. Predictability of parental care may be a distinguishing feature of different forms of ELA, and the degree of predictability afforded by these manipulations may contribute to the diversity of outcomes observed across models. Further, questions remain as to whether differing levels of predictability may contribute to differential effects on neurodevelopment and expression of genes associated with risk for pathology. Here, we tested the hypothesis that changes in maternal behavior in mice would be contingent on the type of ELA experienced, directly comparing predictability of care in the limited bedding and nesting (LBN) and maternal separation (MS) paradigms. We then tested whether the predictability of the ELA environment altered the expression of corticotropin-releasing hormone (Crh), a sexually-dimorphic neuropeptide that regulates threat-related learning, in the amygdala of male and female mice. The LBN manipulation reliably increased the entropy of maternal care, a measure that indicates lower predictability between sequences of dam behavior. LBN and MS rearing similarly increased the frequency of nest sorties and licking of pups but had mixed effects on other aspects of dam-, pup-, and nest- related behaviors. Increased expression of Crh-related genes was observed in pups that experienced ELA, with gene expression measures showing a significant interaction with sex and type of ELA manipulation. Specifically, MS was associated with increased expression of Crh-related genes in males, but not females, and LBN primarily increased expression of these genes in females, but not males. The present study provides evidence for predictability as a distinguishing feature of models of ELA and demonstrates robust consequences of these differing experience on sex-differences in gene expression critically associated with stress responding and sex differences in risk for pathology.

Note:

Funding Information: The work was supported by the National Institutes of Health RO1-MH115914 (KGB) and RO1- MH115049 (KGB).

Declaration of Interests: No competing financial interests or any other conflicts of interest exist.

Ethical Approval Statement: Pups were weaned and sex segregated at postnatal day (PD) 21. All animal procedures were approved by the Brown University Institutional Animal Care and Use Committee and consistent with the guide for the care and use of animals in research.

Keywords: Early life adversity, entropy, maternal behavior, amygdala, sex-differences, corticotropin-releasing hormone

Suggested Citation

Demaestri, Camila and Gallo, Meghan E. and Mazenod, Elisa and Hong, Alexander T. and Arora, Hina and Short, Annabel K. and Stern, Hal S. and Baram, Tallie Z. and Bath, Kevin G., Resource Scarcity But Not Maternal Separation Provokes Unpredictable Maternal Care Sequences in Mice and Both Upregulate Crh-Associated Gene Expression in the Amygdala. Available at SSRN: https://ssrn.com/abstract=4158328 or http://dx.doi.org/10.2139/ssrn.4158328

Camila Demaestri

Columbia University ( email )

Meghan E. Gallo

Brown University ( email )

Box 1860
Providence, RI 02912
United States

Elisa Mazenod

Brown University - Department of Cognitive, Linguistic and Psychological Sciences ( email )

Alexander T. Hong

University of California, Irvine ( email )

Division of Nephrology, University of California I
101 City Drive South, City Tower, Suite 400-ZOT;40
Orange, CA California 92868-3217
United States

Hina Arora

University of California, Irvine ( email )

Division of Nephrology, University of California I
101 City Drive South, City Tower, Suite 400-ZOT;40
Orange, CA California 92868-3217
United States

Annabel K. Short

University of California, Irvine ( email )

Division of Nephrology, University of California I
101 City Drive South, City Tower, Suite 400-ZOT;40
Orange, CA California 92868-3217
United States

Hal S. Stern

University of California, Irvine - Department of Statistics ( email )

Campus Drive
Irvine, CA California 62697-3125
United States

Tallie Z. Baram

University of California, Irvine, School of Medicine, Department of Pediatrics ( email )

Irvine, CA 92697-4475
United States

University of California, Irvine, School of Medicine, Department of Anatomy/Neurobiology ( email )

Irvine, CA 92697-4475
United States

University of California, Irvine - Department of Neurology ( email )

CA 92697
United States

Kevin G. Bath (Contact Author)

Columbia University ( email )

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