Modulation of olfactory-driven behavior by metabolic signals: role of the piriform cortex
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.
KeywordsOlfaction Piriform Glucose GLUT4 Insulin Kv1.3 Sniffing behavior
We would like to thank Ounsa Ben Hellal, Wesley Joshua Earl, and Abigail Thomas for routine technical assistance and rat husbandry.
This work was supported by the Centre National de la Recherche Scientifique, University Lyon 1, the Laboratoire d’Excellence Cortex (ANR-11-LABX-0042), and the National Institutes of Health (NIH) R01 DC013080 from the National Institutes of Deafness and Communication Disorders (NIDCD). The collaboration was supported by a PALSE grant (Programme Avenir Lyon Saint-Etienne) from the University of Lyon 1; the Robert B. Short Zoology Scholarship, the Brenda Weems Bennison Endowment, and the Pasquale Graziadei Endowment Fund from The Florida State University.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving animals and ethical approval
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Experimental protocols were approved by the Lyon University Animal Experimentation Committee, the French Ministry of Higher Education and Research (APAFIS#9924-20170051614351992 v1), and the Florida State University (FSU) Institutional Animal Care and Use Committee (IACUC) under protocols no. 1427 and 1733. Experiments were carried out in accordance with the European Community Council Directive of November 24, 1986 (86/609/EEC), the American Veterinary Medicine Association (AVMA), and the National Institutes of Health (NIH).
This article does not contain any studies with human participants performed by any of the authors.
- Aime P, Hegoburu C, Jaillard T, Degletagne C, Garcia S, Messaoudi B, Thevenet M, Lorsignol A, Duchamp C, Mouly AM, Julliard AK (2012) A physiological increase of insulin in the olfactory bulb decreases detection of a learned aversive odor and abolishes food odor-induced sniffing behavior in rats. PLoS One 7(12):e51227. https://doi.org/10.1371/journal.pone.0051227 CrossRefPubMedPubMedCentralGoogle Scholar
- Aime P, Palouzier-Paulignan B, Salem R, Al Koborssy D, Garcia S, Duchamp C, Romestaing C, Julliard AK (2014) Modulation of olfactory sensitivity and glucose-sensing by the feeding state in obese Zucker rats. Front Behav Neurosci 8:326. https://doi.org/10.3389/fnbeh.2014.00326 CrossRefPubMedPubMedCentralGoogle Scholar
- Colley BS, Biju KC, Visegrady A, Campbell S, Fadool DA (2007) Neurotrophin B receptor kinase increases Kv subfamily member 1.3 (Kv1.3) ion channel half-life and surface expression. Neuroscience 144(2):531–546. https://doi.org/10.1016/j.neuroscience.2006.09.055 CrossRefPubMedGoogle Scholar
- Djukic B, Casper KB, Philpot BD, Chin LS, McCarthy KD (2007) Conditional knock-out of Kir4.1 leads to glial membrane depolarization, inhibition of potassium and glutamate uptake, and enhanced short-term synaptic potentiation. J Neurosci 27(42):11354–11365. https://doi.org/10.1523/JNEUROSCI.0723-07.2007 CrossRefPubMedGoogle Scholar
- Fadool DA, Tucker K, Perkins R, Fasciani G, Thompson RN, Parsons AD, Overton JM, Koni PA, Flavell RA, Kaczmarek LK (2004) Kv1.3 channel gene-targeted deletion produces “Super-Smeller Mice” with altered glomeruli, interacting scaffolding proteins, and biophysics. Neuron 41(3):389–404. (S0896627303008444 [pii])CrossRefGoogle Scholar
- Gibb AJ, Edwards FA (1994) Patch clamp recording from cells in sliced tissues. In: Microelectrode Techniques. The Plymouth Workshop Handbook, CambridgeGoogle Scholar
- Hegoburu C, Shionoya K, Garcia S, Messaoudi B, Thevenet M, Mouly AM (2011) The RUB cage: respiration–ultrasonic vocalizations–behavior acquisition setup for assessing emotional memory in rats. Front Behav Neurosci 5:25. https://doi.org/10.3389/fnbeh.2011.00025 CrossRefPubMedPubMedCentralGoogle Scholar
- Kapur A, Lytton WW, Ketchum KL, Haberly LB (1997) Regulation of the NMDA component of EPSPs by different components of postsynaptic GABAergic inhibition: computer simulation analysis in piriform cortex. J Neurophysiol 78(5):2546–2559. https://doi.org/10.1152/jn.19188.8.131.526 CrossRefPubMedGoogle Scholar
- Kuczewski N, Fourcaud-Trocme N, Savigner A, Thevenet M, Aime P, Garcia S, Duchamp-Viret P, Palouzier-Paulignan B (2014) Insulin modulates network activity in olfactory bulb slices: impact on odour processing. J Physiol 592(13):2751–2769. https://doi.org/10.1113/jphysiol.2013.269639 CrossRefPubMedPubMedCentralGoogle Scholar
- Lacroix MC, Caillol M, Durieux D, Monnerie R, Grebert D, Pellerin L, Repond C, Tolle V, Zizzari P, Baly C (2015) Long-lasting metabolic imbalance related to obesity alters olfactory tissue homeostasis and impairs olfactory-driven behaviors. Chem Senses 40(8):537–556. https://doi.org/10.1093/chemse/bjv039 CrossRefPubMedGoogle Scholar
- Moriyama R, Tsukamura H, Kinoshita M, Okazaki H, Kato Y, Maeda K (2004) In vitro increase in intracellular calcium concentrations induced by low or high extracellular glucose levels in ependymocytes and serotonergic neurons of the rat lower brainstem. Endocrinology 145(5):2507–2515. https://doi.org/10.1210/en.2003-1191 CrossRefPubMedGoogle Scholar
- Paxinos G, Watson C (2013) The rat brain in stereotaxic coordinates, 7th edn. Academic Press, San DiegoGoogle Scholar
- Rankin CH, Abrams T, Barry RJ, Bhatnagar S, Clayton DF, Colombo J, Coppola G, Geyer MA, Glanzman DL, Marsland S, McSweeney FK, Wilson DA, Wu CF, Thompson RF (2009) Habituation revisited: an updated and revised description of the behavioral characteristics of habituation. Neurobiol Learn Mem 92(2):135–138. https://doi.org/10.1016/j.nlm.2008.09.012 CrossRefPubMedGoogle Scholar
- Riera CE, Tsaousidou E, Halloran J, Follett P, Hahn O, Pereira MMA, Ruud LE, Alber J, Tharp K, Anderson CM, Bronneke H, Hampel B, Filho CDM, Stahl A, Bruning JC, Dillin A (2017) The Sense of Smell Impacts Metabolic Health and Obesity. Cell Metab 26(1):198–211 e195. https://doi.org/10.1016/j.cmet.2017.06.015 CrossRefPubMedGoogle Scholar
- Rudell JB, Rechs AJ, Kelman TJ, Ross-Inta CM, Hao S, Gietzen DW (2011) The anterior piriform cortex is sufficient for detecting depletion of an indispensable amino acid, showing independent cortical sensory function. J Neurosci 31(5):1583–1590. https://doi.org/10.1523/JNEUROSCI.4934-10.2011 CrossRefPubMedPubMedCentralGoogle Scholar
- Thiebaud N, Johnson MC, Butler JL, Bell GA, Ferguson KL, Fadool AR, Fadool JC, Gale AM, Gale DS, Fadool DA (2014) Hyperlipidemic diet causes loss of olfactory sensory neurons, reduces olfactory discrimination, and disrupts odor-reversal learning. J Neurosci 34(20):6970–6984. https://doi.org/10.1523/JNEUROSCI.3366-13.2014 CrossRefPubMedPubMedCentralGoogle Scholar
- Venner A, Karnani MM, Gonzalez JA, Jensen LT, Fugger L, Burdakov D (2011) Orexin neurons as conditional glucosensors: paradoxical regulation of sugar sensing by intracellular fuels. J Physiol 589(Pt 23):5701–5708. https://doi.org/10.1113/jphysiol.2011.217000 CrossRefPubMedPubMedCentralGoogle Scholar