Effect of prenatal exposure to alcohol on the distribution and time of origin of corticospinal neurons in the rat

The distribution and the time of origin of corticospinal neurons were examined in rats prenatally exposed to ethanol and in control rats. The distribution of corticospinal neurons was determined by tracing the retrograde transport of horseradish peroxidase (HRP) from an injection site in the cervical spinal cord. In control rats, HRP-positive neurons were distributed in layer Vb throughout motor area 4, rostral motor area 6/8, dorsal somatosensory area 3, caudal somatosensory area 2, and various "association" regions including parietal areas 14, 39, and 40, occipital areas 18a and 18b, cingulate areas 24a and 24b, and prefrontal area 32. In ethanol-exposed rats, the distribution of retrogradely labeled neurons was similar to control animals with three notable exceptions: (1) HRP-positive neurons were evident throughout the rostrocaudal extent of area 6/8; (2) occasionally ectopic labeled neurons were identified in the supragranular layers, layers Va and Vc, and superficial layer VI; and (3) the density of HRP-labeled neurons and the ratio of labeled neurons to the total number of neurons in areas 4, 6/8, 3 and 2 were significantly greater (20-48%) in ethanol-exposed rats than in controls. There was, however, no intergroup difference in the area of the cell bodies of HRP-positive neurons. Taken together, these findings indicate that ethanol exposure resulted in an increased number of corticospinal neurons. The time of origin of corticospinal neurons was determined by using a technique that combined tritiated thymidine autoradiography and retrograde transport of HRP. In control animals, HRP-positive neurons were double labeled by an injection of tritiated thymidine on gestational day (GD) 15, 16, or 17. In ethanol-exposed rats, corticospinal neurons were generated on GD 16, 17, and 18, the late-generated ones being distributed in caudal area 6/8. These intergroup differences represent a persisting ethanol-induced alteration of cortical structure that may underlie motor dysfunction and mental retardation in fetal alcohol-affected offspring. Moreover, the increase in the number and the delay in the time of origin of corticospinal neurons suggest that the normal process of paring down exuberant corticospinal projections may be affected by prenatal exposure to ethanol.