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

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.

Sex Differences in Affective Dysfunction and Alterations in Parvalbumin in Rodent Models of Early Life Adversity

“…Here, we detail that the two of the most prominent models of ELA, MS and LB, have markedly different effects on PV outcomes both acutely and in the long-term. LB models have led to increases in PV in the PFC (Bath et al, 2016 ; Manzano-Nieves et al, 2020 ) of male mice, and the OFC of female, but not male rats (Goodwill et al, 2018 ). Conversely, MS leads to a general decrease in PV in the PFC (Leussis et al, 2012 ; Wieck et al, 2013 ; Ganguly et al, 2015 ) and HPC (Katahira et al, 2018 ; Murthy et al, 2019 ) of rats, which differs based on sex (see Table 1 ).…”

“…Specifically, MS has been associated with a decrease in PV cells in the HPC (Katahira et al, 2018 ; Murthy et al, 2019 ), the BLA (Lukkes et al, 2017 ; Gildawie et al, 2020 ), and the PFC (Leussis et al, 2012 ; Wieck et al, 2013 ; Ganguly et al, 2015 ). Conversely, LB has been associated with an increase in PV in the BLA (Manzano-Nieves et al, 2020 ), PFC (Manzano-Nieves et al, 2020 ), and HPC (Bath et al, 2016 ). However, decreased PV following LB has been observed in the OFC of females but not males (Goodwill et al, 2018 ).…”

Environmental influences on the pace of brain development

“…Although the limited bedding paradigm fails to capture many of the social, emotional and cognitive aspects of being raised in a low-SES environment, this constraint does result in fragmented and unpredictable nurturing behaviours and increased glucocorticoid release in the pups 96 , 97 . Offspring of the dams exposed to this paradigm show earlier declines in the levels of markers of postnatal neurogenesis in the hippocampus, earlier increases in the levels of markers of synaptic maturity, earlier increases in the level of myelin basic protein and impairments in cognitive function 98 – 100 . They also show an initial increase in neuronal proliferation in the hippocampus in early life, but at later times show reduced numbers of neurons and reduced hippocampal volume, suggestive of an earlier peak in neurogenesis 101 .…”

Concurrent environmental enrichment and chronic restraint stress: Effects on innate anxiety and depressive‐like behavior in male adolescent mice

“…In the present study, the increased anxiety only appeared in RS 8 h for 2‐W‐T but not for 4‐W‐T, this result suggests the complexity of behavior consequence upon varies RS treatment. Besides the duration and daily length of RS, the age at the time of testing may be another potential factor since different developmental age has shown different behavioral sensitivity to environmental stimulus (Locci, Geoffroy, Miesch, Mensah‐Nyagan, & Pinna, 2017; Manzano‐Nieves, Bravo, Baskoylu, & Bath, 2020; Miller, Caruso, & Kamens, 2019).…”