Fig. 4: Serpinb2⁺ neurons mediate food intake via LH projection.

a,b, Diagram of injection of the NAc Serpinb2⁺ neurons with AAV-hSyn-FLEx-mGFP-2A-synaptophysin-mRuby (a) and the expression FLEx-mGFP in the NAcSh (b). Scale bar, 100 μm. One technical replicate of three biological replicates. c, Top, Serpinb2⁺ neuron projection to the LH. Scale bar, 500 μm. Bottom, enlarged image of the top square. Square in the right is an enlargement of the left. Arrows indicate the colocalization. Scale bar, 50 μm. d, Diagram of retrograde tracing approach. e, Left, validation of injection site of CTB-555 in the hypothalamus. Middle, validation of injection site of DIO-ChR2-eYFP in the NAcSh. Right, colocalization of retrograde tracing of LH neurons with CTB-555, with the Serpinb2⁺ neurons labeled by AAV-DIO-ChR2-eYFP. Scale bars, 200 μm (left), 100 μm (middle), 30 μm (right). n = 4 mice. f,g, Diagram illustrating the indicated AAV injection into NAc and optic cannulas implantation in the LH area (f) and histology validating virus expression and cannula implantation site (g). Scale bar, 200 μm. h, Optogenetic activation (left) or inhibition (right) of NAc^Serpinb2+→LH neurons, respectively increasing or decreasing food intake. n = 8 mice per group. Two-tailed, unpaired t-test, t₁₄ = 6.195 (left), t₁₄ = 4.773 (right). Data in h are presented as mean ± s.e.m. 3V, third ventricle; AHN, anterior hypothalamic nucleus; AHP, anterior hypothalamic area, posterior part; DMH, ventromedial hypothalamic nucleus; HY, hypothalamus; VMH, ventromedial hypothalamic nucleus; ZI, zona incerta.

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