7%), which was significant

compared to the intact hemisphere (t35 = −18.8, P < 0.0001). The denervation was most pronounced in the dorsal part, including to the CPu, which is the main target of the TH+ cells in the SN (−75.2 ± 21.6%; t35 = −20.9, P < 0.0001), and overall less severe in the ventral part, corresponding to the VTA-innervated NAc (−50.8 ± 23.4%; t35 = −13, P < 0.0001). From the scatter plots in Fig. 4 one can see that the loss of TH+ innervation in the whole striatum was highly correlated with the overall cell loss measured by stereology in the midbrain (SN and VTA combined; R2 = 0.52, P < 0.0001; Fig. 4A), and that the loss of TH+ innervation in the dorsal striatum (CPu) was highly correlated with the TH+ cell loss in the SN (R2 = 0.61, P < 0.0001; ICG-001 mouse Fig. 4B). The denervation of the ventral striatum, on the other hand, was less well correlated with the TH+

cell loss in the Pifithrin-�� purchase VTA (R2 = 0.34, P < 0.0001; Fig. 4C). Deficits in motor function were evaluated in the two drug-induced rotational asymmetry tests, amphetamine- and apomorphine-induced rotation, which are the most commonly used motor tests in unilaterally lesioned mice, and in two tests of spontaneous motor performance, the stepping and cylinder tests, which are standard tools in 6-OHDA-lesioned rats but are less commonly used in mice. In addition, we wanted to validate a novel motor performance test, the so-called corridor task (Dowd et al., 2005a), which so far has not been used for assessment PIK-5 of motor impairments in mice. In Fig. 5, the performance of the individual 6-OHDA-lesioned mice in each of the five tests is plotted against the striatal TH+ innervation density (in panels A–E), and against the total number of

TH+ cells in SN and VTA combined (in panels F–J). Linear regression analysis showed that the corridor task had the best predictive value for both striatal denervation (R2 = 0.46, P < 0.0001; Fig. 5A) and TH+ cell loss in the midbrain (R2 = 0.29, P < 0.0001; Fig. 5F), followed by the apomorphine-induced rotation test (striatal denervation: R2 = 0.45, P < 0.0001; TH+ cell loss: R2 = 0.28, P < 0.0001; Fig. 5B and G). The scores recorded in the amphetamine-induced rotation test showed a significant correlation with both striatal denervation (R2 = 0.44, P < 0.0001; Fig. 5C) and TH+ cell loss (R2 = 0.23, P < 0.05; Fig. 5H). Closer inspection of the plots, however, reveals that this measure has much less predictive value than the two other tests. The impairment seen in the stepping test showed no correlation with striatal denervation (R2 = 0.08, P = 0.14, n.s; Fig. 5D) and only very weak correlation with the TH+ cell loss (R2 = 0.16, P < 0.05; Fig. 5I). The cylinder test, finally, showed only weak correlation with striatal denervation (R2 = 0.14, P < 0.05; Fig. 5E) and no correlation with TH+ cell loss (R2 = 0.04, P = 0.24, n.s; Fig. 5J).