Neurogenesis of Dopaminergic Neurons in the Adult Mammalian Olfactory Bulb: A Possible Source of Cells for Neural Repair Strategies

Contrary to previously held beliefs, the adult brain is in fact capable of generating new neurons that can integrate into its complex circuitry. Recent researches have demonstrated that neurogenesis constitutively occurs in two specific regions of the adult mammalian brain, olfactory bulb (OB) and hippocampus. In the OBthere is a significant number of dopaminergic (DA) precursors, originated from the subventricular zone and migrated following the rostral migratory stream. The properties of these cells has been studied with the patch-clamp technique in a transgenic animalmodel expressing GFP under the tyrosine hydroxylase (TH) promoter. Using BrdU we have first demonstrated that, in regions not normally occupied by DA neurones (mitral and external plexiform layers, ML and EPL) there are cells in which the transcription of the TH gene occurs in the absence of significant translational activity. We have studied the functional properties of these cells, showing that they seem to reflect different degree of maturation towards the DA phenotype as they become progressively closer to their final destination, the glomerular layer. In fact, cells in the EPL are autorhythmic, as are mature DA neurons in the glomerular layer, whereas TH-GFP cells in the ML are not. Furthermore, the cells in the EPL are synaptically connected to the olfactory nerve, whereas those in the ML are not. A new technique, based on dielectrophoresis, is being developed to sort immature DA neurones. It is hoped that these cells, present in a region easily accessible with surgical techniques, expanded in vitro and induced to differentiate towards the DA phenotype, could be a convenient source of neurons for cellular replacement strategies to treat neurodegenerative diseases affecting DA systems