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Updated: May 21, 2026

Social Threat-Safety Test Uncovers Psychosocial Stress-Related Phenotypes
Published on: December 15, 2023
Disrupted cortical function underlies behavior dysfunction due to social isolation
Tomoyuki Miyazaki1, Kenkichi Takase, Waki Nakajima
1Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Insights
Neonatal social isolation disrupts brain development, impairing synaptic plasticity and leading to long-term behavioral deficits in rodents. This stress response affects crucial molecular pathways in the developing brain.
Area of Science:
- Neuroscience
- Developmental Biology
- Behavioral Science
Background:
- Early life stress profoundly impacts lifelong emotional and cognitive behaviors.
- Mechanisms linking neonatal stress to brain circuit formation remain unclear.
Purpose of the Study:
- Investigate how neonatal social isolation affects molecular, cellular, and circuit development in the brain.
- Elucidate the impact of stress on synaptic plasticity and behavior.
Main Methods:
- Studied the effects of neonatal social isolation on rodent barrel cortex development.
- Assessed long-term potentiation and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking.
- Measured stress hormone levels and calcium/calmodulin-dependent protein kinase type II (CaMKII) signaling.
Main Results:
- Neonatal isolation inhibited long-term potentiation and AMPA receptor trafficking.
- Increased stress glucocorticoid hormones mediated this inhibition.
- Reduced CaMKII signaling led to attenuated whisker sensitivity and impaired whisker-dependent behavior.
Conclusions:
- Neonatal social isolation disrupts neuronal plasticity and cortical circuit establishment.
- Altered molecular and cellular processes underlie long-lasting behavioral effects of early stress.
Abstract:
Stressful events during early childhood can have a profound lifelong influence on emotional and cognitive behaviors. However, the mechanisms by which stress affects neonatal brain circuit formation are poorly understood. Here, we show that neonatal social isolation disrupts molecular, cellular, and circuit developmental processes, leading to behavioral dysfunction. Neonatal isolation prevented long-term potentiation and experience-dependent synaptic trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors normally occurring during circuit formation in the rodent barrel cortex. This inhibition of AMPA receptor trafficking was mediated by an increase of the stress glucocorticoid hormone and was associated with reduced calcium/calmodulin-dependent protein kinase type II (CaMKII) signaling, resulting in attenuated whisker sensitivity at the cortex. These effects led to defects in whisker-dependent behavior in juvenile animals. These results indicate that neonatal social isolation alters neuronal plasticity mechanisms and perturbs the initial establishment of a normal cortical circuit, which potentially explains the long-lasting behavioral effects of neonatal stress.
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