CB1R agonist WIN55,212,2 modulates MCH neuronal activity. A, The application of WIN55,212,2 to the lateral hypothalamus depolarized MCH neurons. Some spontaneously active MCH-expressing cells increased their spike frequency when WIN55,212,2 was applied to the slice [trace 1; resting membrane potential (RMP), −60.5 mV]. B, In silent MCH neurons, WIN55,212,2 usually affected only the membrane potential (trace 2 in A; RMP, −62.8 mV). C, D, The effect of WIN55,212,2 on MCH membrane potential was not observed in the presence of the selective CB1R antagonist AM251 (trace 3 in A; RMP, −63.4 mV; population graph in C) or when the slice was perfused with the GABA_A receptor antagonist Bic (trace 4 in A; RMP, −61.8 mV; graph in D). E, Bic application also depolarized MCH cells, suggesting that these hypothalamic neurons are under tonic inhibitory control mediated by GABA_A receptor activation. F, Bar graph summarizing the actions of CB1R agonist/antagonist and Bic on MCH membrane potential. Error bars indicate SEM. Win, WIN55,212,2; Ctrl, control; Win/AM251, in the presence of AM251, the change of membrane induced by WIN55,212,2; Win/Bic, with bicuculline in the bath, the change of membrane potential by additional application of WIN55,212,2; Memb pot, membrane potential.