Modulation of olfactory-driven behavior by metabolic signals: role of the piriform cortex

Brain Struct Funct. 2019 Jan;224(1):315-336. doi: 10.1007/s00429-018-1776-0. Epub 2018 Oct 13.


Olfaction is one of the major sensory modalities that regulates food consumption and is in turn regulated by the feeding state. Given that the olfactory bulb has been shown to be a metabolic sensor, we explored whether the anterior piriform cortex (aPCtx)-a higher olfactory cortical processing area-had the same capacity. Using immunocytochemical approaches, we report the localization of Kv1.3 channel, glucose transporter type 4, and the insulin receptor in the lateral olfactory tract and Layers II and III of the aPCtx. In current-clamped superficial pyramidal (SP) cells, we report the presence of two populations of SP cells: glucose responsive and non-glucose responsive. Using varied glucose concentrations and a glycolysis inhibitor, we found that insulin modulation of the instantaneous and spike firing frequency are both glucose dependent and require glucose metabolism. Using a plethysmograph to record sniffing frequency, rats microinjected with insulin failed to discriminate ratiometric enantiomers; considered a difficult task. Microinjection of glucose prevented discrimination of odorants of different chain-lengths, whereas injection of margatoxin increased the rate of habituation to repeated odor stimulation and enhanced discrimination. These data suggest that metabolic signaling pathways that are present in the aPCtx are capable of neuronal modulation and changing complex olfactory behaviors in higher olfactory centers.

Keywords: GLUT4; Glucose; Insulin; Kv1.3; Olfaction; Piriform; Sniffing behavior.

MeSH terms

  • Action Potentials
  • Animals
  • Behavior, Animal* / drug effects
  • Discrimination, Psychological
  • Energy Metabolism* / drug effects
  • Female
  • Glucose / administration & dosage
  • Glucose Transporter Type 4 / metabolism
  • Habituation, Psychophysiologic
  • Hypoglycemic Agents / administration & dosage
  • Insulin / administration & dosage
  • Kv1.3 Potassium Channel / metabolism
  • Male
  • Mice
  • Odorants*
  • Olfactory Perception* / drug effects
  • Piriform Cortex / cytology
  • Piriform Cortex / drug effects
  • Piriform Cortex / metabolism*
  • Potassium Channel Blockers / pharmacology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism*
  • Rats, Wistar
  • Receptor, Insulin / metabolism
  • Scorpion Venoms / pharmacology
  • Smell* / drug effects


  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • Insulin
  • Kcna3 protein, rat
  • Kv1.3 Potassium Channel
  • Potassium Channel Blockers
  • Scorpion Venoms
  • Slc2a4 protein, rat
  • margatoxin
  • Receptor, Insulin
  • Glucose