Local accumbens in vivo imaging during deep brain stimulation reveals a strategy-dependent amelioration of hedonic feeding

Proc Natl Acad Sci U S A. 2022 Jan 4;119(1):e2109269118. doi: 10.1073/pnas.2109269118.

Abstract

Impulsive overeating is a common, disabling feature of eating disorders. Both continuous deep brain stimulation (DBS) and responsive DBS, which limits current delivery to pathological brain states, have emerged as potential therapies. We used in vivo fiber photometry in wild-type, Drd1-cre, and A2a-cre mice to 1) assay subtype-specific medium spiny neuron (MSN) activity of the nucleus accumbens (NAc) during hedonic feeding of high-fat food, and 2) examine DBS strategy-specific effects on NAc activity. D1, but not D2, NAc GCaMP activity increased immediately prior to high-fat food approach. Responsive DBS triggered a GCaMP surge throughout the stimulation period and durably reduced high-fat intake. However, with continuous DBS, this surge decayed, and high-fat intake reemerged. Our results argue for a stimulation strategy-dependent modulation of D1 MSNs with a more sustained decrease in consumption with responsive DBS. This study illustrates the important role in vivo imaging can play in understanding effects of such novel therapies.

Keywords: deep brain stimulation; fiber photometry; hedonic feeding; nucleus accumbens; responsive neurostimulation.

Publication types

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

MeSH terms

  • Animals
  • Brain / physiology*
  • Deep Brain Stimulation / methods*
  • Feeding Behavior / physiology*
  • Impulsive Behavior
  • Mice
  • Mice, Inbred C57BL
  • Nucleus Accumbens / physiology
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism

Substances

  • Drd1 protein, mouse
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2