Food Restriction Engages Prefrontal Corticostriatal Cells and Local Microcircuitry to Drive the Decision to Run versus Conserve Energy

Adrienne N. Santiago, Emily A. Makowicz, Muzi Du, Chiye Aoki

Research output: Contribution to journalArticlepeer-review

Abstract

Food restriction (FR) evokes running, which may promote adaptive foraging in times of food scarcity, but can become lethal if energy expenditure exceeds caloric availability. Here, we demonstrate that chemogenetic activation of either the general medial prefrontal cortex (mPFC) pyramidal cell population, or the subpopulation projecting to dorsal striatum (DS) drives running specifically during hours preceding limited food availability, and not during ad libitum food availability. Conversely, suppression of mPFC pyramidal cells generally, or targeting mPFC-to-DS cells, reduced wheel running specifically during FR and not during ad libitum food access. Post mortem c-Fos analysis and electron microscopy of mPFC layer 5 revealed distinguishing characteristics of mPFC-to-DS cells, when compared to neighboring non-DS-projecting pyramidal cells: 1) greater recruitment of GABAergic activity and 2) less axo-somatic GABAergic innervation. Together, these attributes position the mPFC-to-DS subset of pyramidal cells to dominate mPFC excitatory outflow, particularly during FR, revealing a specific and causal role for mPFC-to-DS control of the decision to run during food scarcity. Individual differences in GABAergic activity correlate with running response to further support this interpretation. FR enhancement of PFC-to-DS activity may influence neural circuits both in studies using FR to motivate animal behavior and in human conditions hallmarked by FR.

Original languageEnglish (US)
Pages (from-to)2868-2885
Number of pages18
JournalCerebral cortex (New York, N.Y. : 1991)
Volume31
Issue number6
DOIs
StatePublished - May 10 2021

Keywords

  • DREADD
  • GABA
  • anorexia
  • prefrontal cortex
  • striatum

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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