Figure 2.

Sirt1 inhibition affects synaptic inputs and mitochondrial number in POMC neurons in the hypothalamus. In a, EX-527 (i.c.v.) was administered to wild-type adult mice at the beginning of the dark cycle and synaptic inputs were measured on POMC neurons 4 h later. EX-527 decreased the recruitment of inputs onto POMC neurons, mainly affecting symmetric, putatively inhibitory, inputs, and not asymmetric, putatively excitatory synapses. Data are mean ± SEM; n = 15–21 cells. b, Electrophysiological recordings showing decreased frequency of mIPSCs in POMC-GFP neurons treated with EX-527 (mean ± SEM, n = 12 cells). c–f, Sirt1 inhibition by EX-527 affects mitochondrial density in POMC neurons. Sirt1 inhibition increased mitochondrial density (c) and relative area (d) in POMC cells (mean ± SEM, n = 13–20 cells), without affecting indexes of mitochondrial morphology, specifically the cross-sectional mitochondrial area (e) and circularity (f) (data are median ± interquartile range, n > 500). *p < 0.05; **p < 0.01.