Figure 10. Inhibition of striatal HCN channels disrupts MOR-mediated LTD.

A, representative eEPSC traces showing the effects of 25 μM ZD7288 before, during and after DAMGO (0.3 μM, 5 min) application. B–D, HCN channel inhibition disrupted glutamatergic MOR-LTD (104 ± 6%, unpaired t test, P = 0.000498, t16 = 4.67) in the DLS, showing no changes in eEPSC amplitude after DAMGO bath application (0–10 min baseline vs. final 10 min of recording; paired t test, P = 0.635, t7 = 0.496, n = 8 neurons from four mice). E, representative synaptic current traces from C57BL/6J mice showing the spontaneous excitatory postsynaptic currents (sEPSC) in absence (black trace) or presence of 25 μM ZD7288 (grey trace, 15 min) application. F–I, HCN channel inhibition increased frequency (paired t test, P = 0.00600, t18 = 3.113, n = 19 neurons from three mice) and decreased amplitude (paired t test, P < 0.0001, t18 = 5.88, n = 19 neurons from three mice), without changes in rise (paired t test, P = 0.608, t18 = 0.522, n = 19 neurons from three mice) and decay times (paired t test, P = 0.205, t18 = 1.314, n = 19 neurons from three mice) of the sEPSC events in DLS. Time course data represent means ± SEM. Box plots show average of the final 10 min of recording and represent median and interquartile ranges. ns = not significant, **P < 0.001, ***P < 0.001, ****P < 0.0001.