During the prior year we demonstrated that there are distinct forms of Drd1a-mediated activation of ERK (receptor coupled kinase) signaling in the dorsal striatum and the nucleus accumbens (Gerfen et al., 2008). Using Drd1a- and DARPP32-deficient transgenic mice we show that in the dopamine intact accumbens, psychostimulants activate ERK1/2 via a Drd1a- and DARPP32-dependent mechanism. This mechanism is activated in the dorsal striatum only following dopamine depletion as occurs in Parkinson's Disease. Work done during the past year is a continuation of studies to determine the affects of Drd1a-mediated activation of ERK1/2 in the striatum. To this end we have developed a transgenic mouse model in which ERK1 and ERK2 are deleted in the different subpopulations of striatal neurons. Developing these mice has taken over 4 years of intensive work and we are now at the stage of having the mice available to use them in animal models of Parkinson's Disease with L-DOPA induced dyskinesia. Further work on the cellular mechanisms underlying neurologic and pscyhiatric disorders is limited by the fact that neurons throughout the brain utilize common mechanisms for critical functions such as synaptic plasticity, whereas specific neural systems are affected in different disorders. A large part of the Laboratory is now working with the Gene Expression Nervous System Atlas (GENSAT) project ( funded by NINDS and NIMH ) to produce transgenic mice with Cre-recombinase under the regulation of promoters to drive expression in specific neuron populations. Our part of this work is to characterize the expression of Cre in the brains of such transgenic lines and to provide such lines to the Mutant Mouse Regional Resource Center (MMRRC) for distribution to the research community. In the past year we characterized 50 Cre driver lines and are in the process of characterizing 75 lines for the current year ( Gong et al., 2007)