Figure 1. Expression and activation of the hM₃D_q transgene.

A) Transgenic mice used in this study carry the 2 transgenes shown allowing Dox regulated and neural activity dependent expression of the hM₃D_q receptor. B) Overall spatial expression profile of the hM₃D_q transgene in mice off dox maintained in the homecage. Immunofluorescence was strong in hippocampus, basalateral amygdala, and throughout the cortex. Fluorescence was also observed to a small extent in the pontine nucleus and in brainstem. C) Expression in the CA1 region of the hippocampus showing sparse and distributed expression of the hM₃D_q transgene. D) CNO injection causes increased neural activity in hM₃D_q^fos mice. Red curve shows multi unit activity (MUA) recorded from dorsal CA1of an anesthetized hM₃D_q^fos mouse over time. Inset gives fold increase in MUA (4.76 for hM₃D_q^fos vs. .9 for WT, mean 30-40 minutes post-injection/mean pre-injection baseline. n=6 and 6, *=Wilcoxon signed-rank: P<0.01). E & F) cfos induction 1.5 hours after CNO administration in a control (left) and hM₃D_q^fos (right) mouse. hM₃D_q^fos mice showed on average a 2.5-fold increase in cfos expression in the hippocampal CA1 region compared to control mice (see supplementary table 1 hM₃D_q^fos n = 10, control, n = 10, T-test p <.02).