[P1.69]: Prenatal exposure to a cannabinoid agonist results in persistent behavioral deficits and hippocampal dendritic abnormalities in the young and adult rat

formation of mDAs, we used a conditional mouse genetics approach. First, we performed fate-mapping experiments which determined that the Sonic hedgehog (Shh) producing progenitor cells give rise to all midbrain dopamine neurons. Then, we used Shh(Cre to delete the Dicer enzyme, which is critical for microRNA biogenesis. Since Dicer is necessary for proper microRNA processing, we effectively removed all functionally mature microRNAs from the dopamine progenitor pool. Our results indicate that these conditional mutants have a marked reduction in the total number of dopamine neurons and corresponding projections to the striatum by 18.5 days post coitus (dpc). Moreover, in the Dicer conditional knock out the dopamine progenitors continue to proliferate until 16.5 dpc, well beyond the normal neurogenetic interval for dopamine neurons. This data suggests that without microRNAs a significant population of dopamine progenitors remain in the cell cycle instead of differentiating in to mature dopamine neurons. Therefore, we conclude that microRNAs are essential for the accurate coordination of midbrain dopaminergic neurogenesis and maturation.