Data are expressed as mean ± SEM, unless otherwise stated. Details on brains fixation, immunofluorescence, electron microscopy, Tenofovir supplier and camera lucida reconstructions are given in the Supplemental Information. The authors thank R. Hauer, L. Norman, and K. Whitworth for excellent technical assistance. B.R. Micklem helped creating figures. J.-M. Fritschy and P. Greengard and A. Nairn kindly provided antibodies (anti-GABAAR-α1 and anti-DARPP-32, respectively). Y. Dalezios, Linda Katona, and D. Lapray are acknowledged for their help with statistical analysis. We are most grateful to P. Somogyí for his guidance throughout the study, particularly on the collection and interpretation of anatomical

data, and Adriamycin ic50 for his comments on the paper. We also thank C. Herry, M. Mańko, O. Paulsen, A. Sharott, and R. Stewart for critically commenting on earlier versions of the manuscript. This work was supported by the Medical Research Council, UK to M.C. (MRC award U138197106) and P.J.M. (MRC award U138197109), the Austrian

Science Fund-Fonds zur Förderung der wissenschaftlichen Forschung (FWF) grant S10207 and W01206-10 to F.F. and by the Academic Research Collaboration Program of the British Council to F.F. and M.C. T.C.M.B. was funded by an MRC DPhil studentship, and is a fellow of Ecole de l’Inserm Liliane Bettencourt MD-PhD Program, France. All the authors participated in designing the study. Experiments were performed by T.C.M.B. (in vivo recordings, histological processing, neuron identification) and D.B. (electron microscopy, neuron reconstructions). P.J.M., F.F., and M.C. supervised the project. All the authors analyzed the data. T.C.M.B., P.J.M., F.F., and M.C. wrote the paper. All the authors commented on the paper and agreed on the

final version of the manuscript. “
“Functional dichotomy in striatal projection neurons is pivotal for the hugely influential “direct/indirect pathways” model of basal ganglia (BG) organization (Albin et al., 1989, Bergman et al., 1990, Gerfen and Surmeier, 2011, Smith et al., 1998 and Wichmann and DeLong, 1996). Two major types of medium-sized densely-spiny neuron (MSN) preferentially innervate either external globus pallidus (GPe) or BG output heptaminol nuclei (the internal globus pallidus, also known as the entopeduncular nucleus [EPN] in rodents, and the substantia nigra pars reticulata [SNr]). They are further distinguished by distinct electrophysiological properties, selective expression of neuropeptides and dopamine receptors, and their opposing influences on behavior (Gerfen and Surmeier, 2011 and Kravitz et al., 2010). Dopamine balances these two striatal outputs, and its loss in Parkinson’s disease (PD) promotes functional extremes, with disastrous behavioral consequences (Albin et al., 1989 and Wichmann and DeLong, 1996).