Chemogenetic inhibition of IC GABA neurons alters E/I ratio in IC-SN neurons. (A) A KOR-derived DREADD (KORD) was expressed unilaterally in the IC of vGAT-cre mice and IC-SN neurons were labeled for whole cell recordings with a retrograde AAV-tdTomato injected into the SN. (B) KORD-expressing vGAT neurons in the IC were robustly hyperpolarized by salvinorin B (SalB, 100 nM) wash-on. (C) Compared to baseline (BL), 10 min bath application of SalB significantly increased spontaneous excitatory postsynaptic current (sEPSC) frequency but not amplitude and (D) reduced spontaneous inhibitory postsynaptic current (sIPSC) frequency but not amplitude in IC-SN cells, (E) resulting in a significant increase in sEPSC/sIPSC (E/I) ratio. (F) Representative traces of sEPSCs (top) and sIPSCs (bottom) at baseline (black) and following SalB (blue) wash-on. (G-J) In non-KORD expressing tissue, SalB did not affect (G) sEPSC frequency or amplitude, (H) sIPSC frequency or amplitude, or (I) E/I ratio in IC-SN neurons. (J) Representative traces of sEPSCs and sIPSCs at baseline (black) and following SalB (blue) wash-on. Females, open circles; males closed circles; n = 2 mice/sex; *p < 0.05, **p < 0.01; BL, baseline; SalB, salvinorin B.