Early life adversity decreases pre-adolescent fear expression by accelerating amygdala PV cell development.

Gabriela Manzano Nieves,Saba Baskoylu,Kevin G Bath,Marilyn Bravo

doi:10.7554/elife.55263

Abstract

Early life adversity (ELA) is associated with increased risk for stress-related disorders later in life. The link between ELA and risk for psychopathology is well established but the developmental mechanisms remain unclear. Using a mouse model of resource insecurity, limited bedding (LB), we tested the effects of LB on the development of fear learning and neuronal structures involved in emotional regulation, the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). LB delayed the ability of peri-weanling (21 days old) mice to express, but not form, an auditory conditioned fear memory. LB accelerated the developmental emergence of parvalbumin (PV)-positive cells in the BLA and increased anatomical connections between PL and BLA. Fear expression in LB mice was rescued through optogenetic inactivation of PV-positive cells in the BLA. The current results provide a model of transiently blunted emotional reactivity in early development, with latent fear-associated memories emerging later in adolescence.

Highlights

Life adversity (ELA) increases the lifetime risk for multiple forms of psychopathology, including anxiety disorders and major depressive disorder (Agid et al, 1999; Draijer and Langeland, 1999; Heim and Nemeroff, 2001; Koenen and Widom, 2009; Widom, 1999)
We found that limited bedding (LB) reared female mice weighed significantly less than control mice at postnatal day (PND) 16, 21, and 28, with differences diminishing by PND 35 (Figure 1B top), while LB reared males weighed significantly less than control male mice at PND 21 and 28 (Figure 1B bottom)
We identify LB effects on the developmental expression of cued fear learning and provide a potential causal link between the neurodevelopmental and behavioral consequences of LB rearing on fear learning and developmental fear expression

Summary

Introduction

Life adversity (ELA) increases the lifetime risk for multiple forms of psychopathology, including anxiety disorders and major depressive disorder (Agid et al, 1999; Draijer and Langeland, 1999; Heim and Nemeroff, 2001; Koenen and Widom, 2009; Widom, 1999). The increased lifetime risk for psychopathology is proposed to be the result of alterations in the developmental trajectories of brain centers regulating emotional learning and emotional expression. In agreement with this prediction, ELA has been shown to drive early engagement of the basolateral amygdala (BLA), a key node supporting emotional processing, threat assessment, and fear learning (Bath et al, 2016; Moriceau et al, 2009).

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Conclusion