Sustained NPY signaling enables AgRP neurons to drive feeding
- University of California, San Francisco, United States
Figures
Figure 1 with 2 supplements
NPY is uniquely required for sustained hunger driven by AgRP neurons.
(a) AgRP neurons are rapidly inhibited by food presentation but nevertheless promote food intake through a sustained hunger signal. (b) System for measuring food intake in response to activation of …
Figure 1—figure supplement 1
Temporal pattern of pellet consumption in response to different pre-stimulation protocols.
(a–f) Raster plot of pellet intake (1 hr) by AgRP- (a), AgRP+ (d), GABA- (b), GABA+ (e), NPY- (c) and NPY+ (f) mice in response to pre-stimulation of variable length. Red color indicates cumulative …
Figure 1—figure supplement 2
Bout analysis of food intake in response to pre-stimulation a-c.
Bout size for food intake (1 hr) by AgRP+ (N = 10) and AgRP- (N = 5) (a), GABA+ (N = 6) and GABA- (N = 8) (b), and NPY+ (N = 7) and NPY- (N = 6) (c) mice in response to pre-stimulation of variable …
Figure 2
NPY, but not GABA or AgRP, is required for the sustained effect of AgRP neuron stimulation on appetitive behavior.
(a) Schematic for progressive ratio three tasks, in which each successive pellet of food requires the mouse to press the lever three more times than the previous pellet. (b) Raster plot showing …
Figure 3
The requirement for NPY is rescued by reexpression of NPY in AgRP neurons.
(a) Experimental setup for optogenetic stimulation with alternating laser ON and OFF epochs. (b) Pattern of pellet consumption for NPY +and NPY- mice in response to alternating laser ON and OFF …
Figure 4 with 1 supplement
AgRP neurons show variable responses to concurrent stimulation in the absence of NPY.
(a) Schematic for measurement of food intake during chemogenetic stimulation of AgRP neurons. (b) Expression of hM3Dq in AgRP neurons. Sample was stained for the HA tag on hM3Dq (magenta). (c) Food …
Figure 4—figure supplement 1
Chemogenetic activation of AgRP neurons induces feeding in mice with or without NPY.
(a) Food intake (1 hr) for NPY+ (hM3Dq+ N = 4; hM3Dq- N = 4) and NPY- (hM3Dq+ N = 6; hM3Dq- N = 4) mice following chemogenetic stimulation (CNO, 0.3 mg/kg) or control treatment. (b) Cumulative …
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Genetic reagent (Mus musculus) | B6; Agrptm1(cre)Lowl/J | Jackson Labs Stock | #012899 | |
| Genetic reagent (Mus musculus) | B6; 129S-Gt(ROSA)26Sortm32(CAG-COP4*H134R/EYFP)Hze/J; | Jackson Labs Stock | #012569 | |
| Genetic reagent (Mus musculus) | B6; Tg (CAG-CHRM3,-mCitrine)1Ute/J | Jackson Labs Stock | #026220 | |
| Genetic reagent (Mus musculus) | B6; Cg-Ay/J | Jackson Labs Stock | #000021 | |
| Genetic reagent (Mus musculus) | Slc32a1tm1Lowl/J | Jackson Labs Stock | #012897 | |
| Genetic reagent (Mus musculus) | 129S-Npytm1Rpa/J | Jackson Labs Stock | #004545 | |
| Antibody | anti-NPY (rabbit monoclonal) | Cell Signaling | 11976 | (1:1000) dilution |
| Recombinant DNA reagent | pAAV-EF1a-DIO-NPY | this paper | NA | plasmid with AAV backbone to express NPY in the presence of Cre recombinase |
Additional files
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Transparent reporting form
- https://doi.org/10.7554/eLife.46348.015
