A tale of two circuits: CCK NTS neuron stimulation controls appetite and induces opposing motivational states by projections to distinct brain regions

Neuroscience. 2017 Sep 1;358:316-324. doi: 10.1016/j.neuroscience.2017.06.049. Epub 2017 Jul 3.

Abstract

Cholecystokinin (CCK)-expressing neurons within the nucleus of the solitary tract (CCKNTS) of the mouse are responsive to satiety signals and their chemogenetic activation suppresses appetite. Optogenetic activation of CCKNTS axon terminals within either the parabrachial nucleus (PBN) or the paraventricular nucleus of the hypothalamus (PVH) is sufficient to suppress feeding. An interesting dichotomy has been revealed when assessing the motivational valence of these two circuits. Activating CCKNTS cell bodies is aversive as demonstrated by conditioned taste aversion and place-preference assays. Activation of the CCKNTS→PBN pathway is also aversive; however, stimulating the CCKNTS→PVH pathway is appetitive when assayed using a real-time, place-preference task. Thus, these two projections from CCKNTS neurons reduce food intake through opposite motivational states; one pathway signals positive valence (CCKNTS→PVH) and the other signals negative valence (CCKNTS→PBN).

Keywords: chemogenetics; cholecystokinin; conditioned place preference; conditioned taste aversion; nucleus tractus solitarius; optogenetics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Appetite / genetics*
  • Avoidance Learning / physiology
  • Channelrhodopsins / genetics
  • Channelrhodopsins / metabolism
  • Cholecystokinin / genetics
  • Cholecystokinin / metabolism*
  • Conditioning, Operant / physiology
  • Eating / genetics
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motivation / physiology*
  • Neural Pathways / physiology*
  • Oncogene Proteins v-fos / metabolism
  • Optogenetics
  • Parabrachial Nucleus / physiology*
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Solitary Nucleus / cytology*
  • Taste / physiology
  • Transduction, Genetic

Substances

  • Channelrhodopsins
  • Luminescent Proteins
  • Oncogene Proteins v-fos
  • red fluorescent protein
  • Cholecystokinin