a, ARC in Agrp-Cre;Pomc-TopazFP mice expressing ChR2:tdTomato in AGRP neurons. b, Left, scheme for testing ARCAGRP→ARCPOMC synaptic connections. Red: ChR2:tdTomato. Right, ARCAGRP→ARCPOMC synaptic currents. Blue: light pulses. c, Synaptic connectivity between AGRP and POMC neurons. Dashed lines: not detected. d, Cell-attached recording (top) and normalised firing rate (bottom, n = 5) from ARCAGRP→ARCPOMC photostimulation in brain slices (with Npy1r, Npy5r, and GABAB receptor antagonists). e, POMC neuron expression of hM4D and GFP from Cre-dependent rAAV. f, Top, hM4D agonism with CNO (10 μM). Bottom, firing rate normalised to baseline (paired t-test, n = 4). g, Intraperitoneal CNO (5 mg/kg) did not increase food intake (1 h) in POMC-hM4D mice (paired t-test, P = 0.32, n = 8). h–j, Occlusion of ARCAGRP→ ARCPOMC inhibition by optical co-stimulation of AGRP and POMC neurons (h) did not impair the feeding response (i,j) (n = 9). Pre, Stim, Post: before, during (blue), after photostimulation (1 h each). Red line: AGRP neuron-evoked food intake from ref. 4. Values are means ± s.e.m. n.s.: not significant, *P < 0.05.