The teratogenic effects of chronic prenatal alcohol exposure have been well documented and are classified as fetal alcohol spectrum disorders (FASD). Of the cognitive deficits associated with FASD, attention deficits are among the most prevalent and persistent, yet there is a limited understanding of the neural mechanisms underlying these deficits. It has been shown that pyramidal neurons in layer VI of the medial prefrontal cortex (mPFC) are critical for optimal attention. The morphological development of these neurons is driven by nicotinic acetylcholine receptors, which are vulnerable to dysregulation by developmental ethanol exposure in rodents. To date, studies of developmental ethanol exposure on mPFC neuronal morphology have been quite limited. In this study, a quantitative Sholl analysis of mPFC layer VI neuron morphology was performed on biocytin-filled neurons using Neurolucida software to produce three-dimensional neuron tracings. Mice of both sexes were exposed to either ethanol vapour or air during the human 2nd and 3rd trimester equivalents, and assessed for neuron morphology at the juvenile-equivalent age of postnatal day 15. Morphological measures analyzed included apical and basal dendritic matter, complexity, and cell body area. Compared to the controls, developmental ethanol exposure decreased the length and complexity of apical dendrites in male mice, but increased the length and complexity of basal dendrites in female mice. This demonstrates a sex difference in developmental ethanol-induced morphological alterations to mPFC layer VI neurons. These findings suggest that exposure to ethanol during development cause structural changes within the mPFC early in postnatal life, which may alter the trajectory of normal morphological refinements during mPFC maturation. Alterations to dendrite morphology may influence the function of the mPFC through changes to the location and type of afferent axonal inputs from other brain areas to layer VI pyramidal cell dendrites. Furthermore, these results provide a potential morphological mechanism underlying attention deficits associated with FASD.
Written By Laura Spatafora, Emma Louth, Charles Sutton, Craig Bailey
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