In this classification lesion severity is defined on basis of the extent of striatal TH+ denervation rather than the degree of TH+ cell loss. The reason for this choice is that the behavioural deficits in the corridor and rotation tests were more closely correlated with extent of striatal denervation than cell loss. This is particularly
the case JQ1 for the identification of mice with severe lesions: all mice with > 80% loss of striatal TH+ innervation showed < 20% pellet retrieval in the corridor test and scored at least 3 turns/min in the apomorphine test (see Fig. 5). Mice with severe lesion-induced deficits were not as easily identified based on the extent of TH+ cell loss. It is notable that mice with almost complete, 90%, TH+ cell loss in SN pars compacta displayed highly variable performance in the corridor and rotation tests (0–40% retrievals in the corridor task and 0–20 turns/min
in the rotation tests; supporting Fig. S1). Maximal behavioural impairment was obtained only when the 6-OHDA lesion involved also part of the VTA: in the cohort of mice studied here, all mice with < 20% pellet retrieval in the corridor test showed a significant (20–70%) loss of TH+ neurons in the VTA (supporting Fig. S2). This suggests that C59 wnt price the entire mesostriatal projection, including cells distributed throughout the SN and VTA, has to be involved by the lesion in order to induce profound motor performance deficits in mice. Once this extent of lesion is achieved, however, our results show that the deficits are highly stable over time. Our data suggest that these selection
criteria can reliably be used to identify mice with > 60% lesion of the mesostriatal projection. The identification of mice with more triclocarban severe lesions, however, is less perfect. In the cohort studied here 4 of the 17 mice that showed a combined score consistent with a severe, > 80%, lesion (< 20% pellet retrieval in the corridor test and 3 contralateral turns/min in the apomorphine test) had a less severe lesion than predicted by this level of impairment, i.e. in the range of 60–80% striatal denervation, as determined by densitometry. In conclusion, we show that the novel corridor task is a highly useful test for the evaluation of lesion-induced sensorimotor deficits in mice with unilateral lesions of the mesostriatal dopamine system, and that this test, in combination with conventional drug-induced rotation tests, can be used to select animals with profound DAergic lesions that are stable over time.