Developmental Studies

Abnormalities occurring during brain development may be responsible for adult alterations in dopamine neurotransmission in the medial prefrontal cortex (mPFC) and ventral striatum (nucleus accumbens, NAcc). Such abnormalities have been linked to psychiatric disorders, including schizophrenia, where under- or malfunction of mPFC dopamine contributes to cognitive symptoms and where sensitized mesolimbic dopamine function contributes to psychotic symptoms. Netrin-1, a member of the mammalian netrin protein family, is a bifunctional guidance cue that, by attracting or repelling growing neurites, directs them toward their appropriate targets. Our group is working on the idea that variations in the function of DCC (deleted in colorectal cancer) and UNC-5 homologues, two netrin-1 receptors highly expressed by dopamine neurons, at specific developmental stages, alter the establishment of mesocortical and mesolimbic dopamine circuitry and influence dopamine function in adulthood. To this end we conduct molecular, neurochemical, neuroanatomical and behavioral experiments throughout the lifespan of rats as well as different lines of transgenic mice. It is hoped that this work will provide information about molecular mechanisms underlying individual differences in susceptibility to psychopathology.