Formation of the neocortex in mice developing in conditions of prenatal serotonin deficiency.

We report here detailed studies of structural changes occurring in the mouse neocortex formed and stratified in conditions of prenatal experimental blockade of serotonin synthesis. Studies were performed using F1(C57BL/CBA) hybrid mice. Endogenous serotonin levels were decreased by exposure of the mice to parachlorophenylalanine, which inhibits the key serotonin synthesis enzyme tryptophan hydroxylase. Offspring brains were studied at 1, 5 and 10 days (n = 10-15 for each time point) of postnatal development. Controls consisted of intact animals at the same periods of development. These experiments showed that prenatal blockade of serotonin synthesis leads to impaired formation of all neocortical layers, impaired growth, development, and differentiation of neurons, and alterations in neuron shape and size. As postnatal development proceeded, significant numbers of neurons died in the brain structures of these animals.