Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit

  1. Giuseppe D'Agostino  Is a corresponding author
  2. David J Lyons
  3. Claudia Cristiano
  4. Luke K Burke
  5. Joseph C Madara
  6. John N Campbell
  7. Ana Paula Garcia
  8. Benjamin B Land
  9. Bradford B Lowell
  10. Ralph J Dileone
  11. Lora K Heisler  Is a corresponding author
  1. University of Aberdeen, United Kingdom
  2. University of Cambridge, United Kingdom
  3. Harvard Medical School, United States
  4. Yale University School of Medicine, United States
4 figures

Figures

CCKNTSneurons are activated by feeding.

(A) Schematic of mouse crossing to generate a CCK-iCre::R26-loxSTOPlox-eYFP mouse line (CckYFP). (B) Representative expression of CckYPF in a NTS coronal section. (C) Quantification of CckYPF-express…

https://doi.org/10.7554/eLife.12225.003
Activation of CCKNTS neurons reduces feeding and body weight.

(A–D) Bilateral stereotaxic injection of Cre-dependent excitatory hM3Dq-mCherry virus into the NTS of male Cck-iCre mice facilitated activation of CCKNTS neurons. (A) Schematic and Cre-mediated …

https://doi.org/10.7554/eLife.12225.004
Figure 3 with 3 supplements
Activation of CCKNTS neurons efferent to the PVH suppresses appetite.

(A) Schematic of CCKNTS→ PVH targeting strategy using bilateral NTS delivery of Cre-dependent ChR2-eYFP expressing vector in Cck-iCre mice. (B) Selective eYFP expression following Cre-mediated …

https://doi.org/10.7554/eLife.12225.005
Figure 3—figure supplement 1
Chemogenetic activation of CCKNTS neurons elicits c-Fos in the paraventricular nucleus of the hypothalamus (PVH).

(A) Schematic and Cre-mediated recombination of hM3Dq-mCherry vector. (B) Cck-iCre-hM3Dq-mCherryNTS mice were food deprived overnight and then treated with a single systemic injection of CNO (0.3 …

https://doi.org/10.7554/eLife.12225.006
Figure 3—figure supplement 2
Hypothalamic projections of CCKNTS neurons.

Representative hypothalamic coronal sections from a Cck-iCre-ChR2-eYFPNTS mouse. Scale bar represents 200 μm. 3v, third ventricle; AHA, anterior hypothalamic (hyp) area, anterior part; AHP, anterior …

https://doi.org/10.7554/eLife.12225.007
Figure 3—figure supplement 3
Subset of PVH MC4R neurons express CCKA receptor and are responsive to CCK.

(A) Schematic of mouse crossing to generate a Mc4r-t2a-Cre::tdTomato mouse line. (B) Schematic of PVH location in a coronal hypothalamic section. (C) CT values for individual Mc4r-t2a-Cre::tdTomato

https://doi.org/10.7554/eLife.12225.008
CCKNTS neurons signal positive valence via the PVH.

(A and D) Experimental strategies for the interrogation of the valence encoded by NTSCCK→PVH terminals. (B) Food-deprived Cck-iCre-ChR2-eYFPNTS mice exhibited a significant place preference for the …

https://doi.org/10.7554/eLife.12225.009

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