Prenatal Ethanol Exposure Impairs Synaptic Function in the Medial Prefrontal Cortex and Causes Attention Deficits in Rats
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Background. Prenatal ethanol exposure (PE) causes multiple behavioral and cognitive deficits, collectively referred to as fetal alcohol spectrum disorders (FASD). Over 50% of FASD children exhibit attention deficits, of which the underlying neural mechanisms are still unclear. The medial prefrontal cortex (mPFC) in rats, corresponding to the dorsolateral PFC in humans, plays a significant role in attentional control. Prenatal ethanol exposure could lead to alterations in neuronal function in the mPFC, contributing to attention deficits in rats. In addition, the deficits may be ameliorated by postnatal environmental intervention. Neonatal handling and environmental enrichment have been proven effective in treating a variety of mental disorders in animal models. Thus, these intervention approaches were investigated in the present study.Methods. Pregnant rats were administered with 15% (w/v) ethanol (6 g/kg/day) during gestational days 8 – 20, and their male offspring were the subjects of this study. A modified 2-choice reaction time (2-CRT) task was used to illustrate attention deficits in PE rats. In vitro whole-cell electrophysiological recordings were performed to examine PE-induced changes in synaptic function in layer V prelimbic cortex, where the major output neurons are located. Moreover, an optogenetic experiment was conducted to assess the relationship between the mPFC dysfunction and attention deficits. We also investigated if enriched rearing, by consecutively applying neonatal handling and post-weaning environmental enrichment, could reverse PE-induced behavioral and neuronal alterations.Results. Prenatal ethanol exposure led to increased impulsive premature responses and augmented lapses of attention shown by greater skewness of reaction time distribution in the 2-CRT task. Electrophysiological recordings in layer V pyramidal neurons in the prelimbic cortex showed an increased excitation/inhibition ratio, which was mediated by enhanced excitatory synaptic strength and unaltered inhibitory synaptic strength. Optogenetic excitation of deep layer mPFC pyramidal neurons led to increased premature responses in naïve rats, mimicking what was observed in PE rats. Additionally, enriched rearing reversed the attention deficits and the enhancement in excitatory synaptic strength in layer V prelimbic cortex in PE rats.Conclusion. Prenatal ethanol exposure causes overexcitability of layer V pyramidal neurons in the prelimbic cortex, which could contribute to attention deficits in PE rats. Enriched rearing in early life is effective in treating the condition. These findings could provide insights into the development of intervention strategies for FASD.