Appetite Controlled by a Cholecystokinin Nucleus of the Solitary Tract to Hypothalamus Neurocircuit

Elife. 2016 Mar 14;5:e12225. doi: 10.7554/eLife.12225.

Abstract

The nucleus of the solitary tract (NTS) is a key gateway for meal-related signals entering the brain from the periphery. However, the chemical mediators crucial to this process have not been fully elucidated. We reveal that a subset of NTS neurons containing cholecystokinin (CCK(NTS)) is responsive to nutritional state and that their activation reduces appetite and body weight in mice. Cell-specific anterograde tracing revealed that CCK(NTS) neurons provide a distinctive innervation of the paraventricular nucleus of the hypothalamus (PVH), with fibers and varicosities in close apposition to a subset of melanocortin-4 receptor (MC4R(PVH)) cells, which are also responsive to CCK. Optogenetic activation of CCK(NTS) axon terminals within the PVH reveal the satiating function of CCK(NTS) neurons to be mediated by a CCK(NTS)→PVH pathway that also encodes positive valence. These data identify the functional significance of CCK(NTS) neurons and reveal a sufficient and discrete NTS to hypothalamus circuit controlling appetite.

Keywords: feeding behavior; mouse; neuronal circuits; neuropeptides; neuroscience.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Appetite*
  • Brain Mapping
  • Cholecystokinin / metabolism*
  • Mice
  • Neural Pathways / anatomy & histology*
  • Optogenetics
  • Paraventricular Hypothalamic Nucleus / physiology*
  • Solitary Nucleus / physiology*

Substances

  • Cholecystokinin