Characterization of the Developing Mouse Dopamine Neuron Phenotype

Abstract

Previous research in adult mice has suggested that neurons are capable of changing their phenotype, long after neurogenesis has come to a halt. In the midbrain, the changing dopamine (DA) neuron phenotype may have implications in neurological disorders such as Parkinson’s disease, addiction, attention deficit hyperactivity disorder and schizophrenia. Using a transgenic mouse model with Cre recombinase expression under control of dopamine transporter (DAT) and yellow fluorescent protein (YFP) Cre reporter, we are able to differentiate between former and current DA neurons in the ventral midbrain. Current DA neurons are identified using tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis; whereas former DA neurons are YFP positive but TH negative suggesting that they expressed dopamine transporter at some point in their lifecycle but are not currently synthesizing dopamine. Using this model in adult transgenic mice, previous research in our lab has revealed that the DA neuron phenotype is regulated by changes in the environment. In this study, mice transgenic for DATCre/YFP were analyzed at different time points during development to better understand when the DA neuron phenotype becomes susceptible to changes in the environment. Preliminary data suggests that in newborn mice, approximately 95% of all dopamine neurons identified in the substantia nigra (SN) were classified as current DA neurons with very few YFP positive, TH negative neurons. In adult mice, however, approximately 41% of DA neurons in the SN were both YFP and TH positive suggesting that as mice age, DA neurons change their phenotype in response to the environment. Generating a developmental timeline will provide a new starting point for further understanding how the changing DA neuron phenotype is implicated in dopamine‐related disorders such as Parkinson’s disease.Support or Funding InformationBrody School of Medicine at East Carolina University