(A) Cartoon illustrating the AAV2/5 reagents and approaches for selectively expressing hM4Di-mCherry or tdTomato (as a control AAV) bilaterally in striatal astrocytes. Once such mice were prepared, behavior was assessed 3 weeks later and 2 hrs after intraperitoneal administration of 1 mg/kg CNO or vehicle.
(B) The representative open-field activity tracks show the 4 experimental groups used in behavioral analyses to control for potential off target effects of CNO and to control for AAV microinjections.
(C) Distance travelled by the mice over 20 min in an open field chamber, divided into 5 min epochs and also pooled over 20 mins for the 4 experimental groups.
(D) Cartoon of the modified open field test with a light stimulus.
(E) Distance travelled in the modified open field chamber before, during and after light stimulation (in 1 min epochs). Notably, the hM4Di + CNO group showed no significant increase in ambulation in response to light stimulation, whereas all the other groups did so.
(F) Behavioral layout of the novel object recognition task for the 4 experimental groups. No significant difference was found between hM4Di + Veh and AAV + Veh groups across all the behavioral tests, but there were clear differences between the AAV + CNO and the hM4Di + CNO groups (B-F).
Data: mean ± s.e.m. Full details of n numbers, precise P values and statistical tests are reported in Supplementary Table 1. * indicates P < 0.05, ** indicates P < 0.01, *** indicates P < 0.001, NS indicates not significantly different. See also Fig S3-4.