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

Area of Science:

• Neuroscience
• Developmental Psychology
• Behavioral Biology

Background:

• Early life adversity (ELA) increases the risk for stress-related disorders.
• The developmental mechanisms linking ELA to psychopathology are not fully understood.
• Resource insecurity is a model for studying ELA effects.

Purpose of the Study:

• To investigate the impact of limited bedding (LB), a model of resource insecurity, on fear learning and emotional regulation circuits.
• To examine the effects of LB on the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) development.
• To elucidate the developmental trajectory of fear memory and emotional reactivity following early life stress.

Main Methods:

• Utilized a mouse model of resource insecurity (limited bedding).
• Assessed auditory conditioned fear memory formation and expression in peri-weanling mice.
• Examined neuronal development, specifically parvalbumin (PV)-positive cells in the BLA and PL-BLA connections.
• Employed optogenetics to investigate the role of PV-positive cells in fear expression.

Main Results:

• Limited bedding (LB) delayed fear memory expression but not formation in young mice.
• LB accelerated the development of PV-positive cells in the BLA and increased PL-BLA connectivity.
• Optogenetic inactivation of BLA PV-positive cells rescued fear expression in LB mice.
• These findings suggest a transient blunting of emotional reactivity followed by latent fear memory emergence.

Conclusions:

• Early life resource insecurity can alter the developmental timing of fear memory expression.
• Changes in BLA and mPFC development, particularly PV cell emergence and PL-BLA connections, are implicated in ELA's effects.
• Targeting specific neuronal populations, like PV-positive cells in the BLA, may offer therapeutic avenues for stress-related disorders stemming from ELA.