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Disrupted cortical function underlies behavior dysfunction due to social isolation.


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 ?-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.

SUBMITTER: Miyazaki T 

PROVIDER: S-EPMC3387818 | biostudies-other | 2012 Jul

REPOSITORIES: biostudies-other

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Disrupted cortical function underlies behavior dysfunction due to social isolation.

Miyazaki Tomoyuki T   Takase Kenkichi K   Nakajima Waki W   Tada Hirobumi H   Ohya Daisuke D   Sano Akane A   Goto Takahisa T   Hirase Hajime H   Malinow Roberto R   Takahashi Takuya T  

The Journal of clinical investigation 20120618 7


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-methylisoxa  ...[more]

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