Brain Structure and Function

, Volume 222, Issue 1, pp 577–586 | Cite as

Activity in the rat olfactory cortex is correlated with behavioral response to odor: a microPET study

  • Philippe Litaudon
  • Caroline Bouillot
  • Luc Zimmer
  • Nicolas Costes
  • Nadine Ravel
Original Article

Abstract

How olfactory cortical areas interpret odor maps evoked in the olfactory bulb and translate odor information into behavioral responses is still largely unknown. Indeed, rat olfactory cortices encompass an extensive network located in the ventral part of the brain, thus complicating the use of invasive functional methods. In vivo imaging techniques that were previously developed for brain activation studies in humans have been adapted for use in rodents and facilitate the non-invasive mapping of the whole brain. In this study, we report an initial series of experiments designed to demonstrate that microPET is a powerful tool to investigate the neural processes underlying odor-induced behavioral response in a large-scale olfactory neuronal network. After the intravenous injection of [18F]Fluorodeoxyglucose ([18F]FDG), awake rats were placed in a ventilated Plexiglas cage for 50 min, where odorants were delivered every 3 min for a 10-s duration in a random order. Individual behavioral responses to odor were classified into categories ranging from 1 (head movements associated with a short sniffing period in response to a few stimulations) to 4 (a strong reaction, including rearing, exploring and sustained sniffing activity, to several stimulations). After [18F]FDG uptake, rats were anesthetized to perform a PET scan. This experimental session was repeated 2 weeks later using the same animals without odor stimulation to assess the baseline level of activation in each individual. Two voxel-based statistical analyses (SPM 8) were performed: (1) a two-sample paired t test analysis contrasting baseline versus odor scan and (2) a correlation analysis between voxel FDG activity and behavioral score. As expected, the contrast analysis between baseline and odor session revealed activations in various olfactory cortical areas. Significant increases in glucose metabolism were also observed in other sensory cortical areas involved in whisker movement and in several modules of the cerebellum involved in motor and sensory function. Correlation analysis provided new insight into these results. [18F]FDG uptake was correlated with behavioral response in a large part of the anterior piriform cortex and in some lobules of the cerebellum, in agreement with the previous data showing that both piriform cortex and cerebellar activity in humans can be driven by sniffing activity, which was closely related to the high behavioral scores observed in our experiment. The present data demonstrate that microPET imaging offers an original perspective for rat behavioral neuroimaging.

Keywords

Olfaction Piriform cortex Sniffing MicroPET [18F]Fluorodeoxyglucose 

Notes

Acknowledgments

This work was supported by the LABEX CORTEX (ANR-11-LABX-0042) and the LABEX PRIMES (ANR-11-LABX-0063) of Université de Lyon, within the program “Investissements d’Avenir” (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures received approval from the Lyon 1 University Ethics Committee (permission BH2012-48).

Informed consent

This article does not contain any studies with human participants performed by any of the authors.

References

  1. Armstrong DM, Drew T (1980) Responses in the posterior lobe of the rat cerebellum to electrical stimulation of cutaneous afferents to the snout. J Physiol 309:357–374CrossRefPubMedPubMedCentralGoogle Scholar
  2. Best C, Lange E, Buchholz H-G et al (2014) Left hemispheric dominance of vestibular processing indicates lateralization of cortical functions in rats. Brain Struct Funct 219:2141–2158. doi: 10.1007/s00429-013-0628-1 CrossRefPubMedGoogle Scholar
  3. Bojsen-Moller F, Fahrenkrug J (1971) Nasal swell-bodies and cyclic changes in the air passage of the rat and rabbit nose. J Anat 110:25–37PubMedPubMedCentralGoogle Scholar
  4. Bosman LWJ, Koekkoek SKE, Shapiro J et al (2010) Encoding of whisker input by cerebellar Purkinje cells. J Physiol 588:3757–3783. doi: 10.1113/jphysiol.2010.195180 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Chabaud P, Ravel N, Wilson DA, Gervais R (1999) Functional coupling in rat central olfactory pathways: a coherence analysis. Neurosci Lett 276:17–20CrossRefPubMedGoogle Scholar
  6. Chapuis J, Garcia S, Messaoudi B et al (2009) The way an odor is experienced during aversive conditioning determines the extent of the network recruited during retrieval: a multisite electrophysiological study in rats. J Neurosci 29:10287–10298. doi: 10.1523/JNEUROSCI.0505-09.2009 CrossRefPubMedGoogle Scholar
  7. Chapuis J, Cohen Y, He X et al (2013) Lateral entorhinal modulation of piriform cortical activity and fine odor discrimination. J Neurosci 33:13449–13459. doi: 10.1523/JNEUROSCI.1387-13.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Chen C-FF, Zou D-J, Altomare CG et al (2014) Nonsensory target-dependent organization of piriform cortex. Proc Natl Acad Sci USA 111:16931–16936. doi: 10.1073/pnas.1411266111 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Cohen Y, Putrino D, Wilson DA (2015) Dynamic cortical lateralization during olfactory discrimination learning. J Physiol 593:1701–1714. doi: 10.1113/jphysiol.2014.288381 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Corballis MC (2008) Of mice and men—and lopsided birds. Cortex 44:3–7. doi: 10.1016/j.cortex.2007.10.001 CrossRefPubMedGoogle Scholar
  11. Courtiol E, Amat C, Thevenet M et al (2011) Reshaping of bulbar odor response by nasal flow rate in the rat. PLoS One 6:e16445. doi: 10.1371/journal.pone.0016445 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Courtiol E, Lefèvre L, Garcia S et al (2014) Sniff adjustment in an odor discrimination task in the rat: analytical or synthetic strategy? Front Behav Neurosci 8:145. doi: 10.3389/fnbeh.2014.00145 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Deschênes M, Moore J, Kleinfeld D (2012) Sniffing and whisking in rodents. Curr Opin Neurobiol 22:243–250. doi: 10.1016/j.conb.2011.11.013 CrossRefPubMedGoogle Scholar
  14. Esclassan F, Courtiol E, Thevenet M et al (2012) Faster, deeper, better: the impact of sniffing modulation on bulbar olfactory processing. PLoS One 7:e40927. doi: 10.1371/journal.pone.0040927 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Fontanini A, Spano P, Bower JM (2003) Ketamine–xylazine-induced slow (<1.5 Hz) oscillations in the rat piriform (olfactory) cortex are functionally correlated with respiration. J Neurosci 23:7993–8001PubMedGoogle Scholar
  16. Fueger BJ, Czernin J, Hildebrandt I et al (2006) Impact of animal handling on the results of 18F-FDG PET studies in mice. J Nucl Med 47:999–1006PubMedGoogle Scholar
  17. Gadziola MA, Tylicki KA, Christian DL, Wesson DW (2015) The olfactory tubercle encodes odor valence in behaving mice. J Neurosci 35:4515–4527. doi: 10.1523/JNEUROSCI.4750-14.2015 CrossRefPubMedGoogle Scholar
  18. Ghosh S, Larson SD, Hefzi H et al (2011) Sensory maps in the olfactory cortex defined by long-range viral tracing of single neurons. Nature 472:217–220. doi: 10.1038/nature09945 CrossRefPubMedGoogle Scholar
  19. Gire DH, Whitesell JD, Doucette W, Restrepo D (2013) Information for decision-making and stimulus identification is multiplexed in sensory cortex. Nat Neurosci 16:991–993. doi: 10.1038/nn.3432 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Grosmaitre X, Santarelli LC, Tan J et al (2007) Dual functions of mammalian olfactory sensory neurons as odor detectors and mechanical sensors. Nat Neurosci 10:348–354. doi: 10.1038/nn1856 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Haberly LB (1973) Summed potentials evoked in opossum prepyriform cortex. J Neurophysiol 36:775–788PubMedGoogle Scholar
  22. Haberly LB (2001) Parrallel-distributed processing in olfactory cortex: new insights from morphological and physiological analysis of neuronal circuitry. Chem Senses 26:551–576. doi: 10.1093/chemse/26.5.551 CrossRefPubMedGoogle Scholar
  23. Haberly LB, Price JL (1977) The axonal projection patterns of the mitral and tufted cells of the olfactory bulb in the rat. Brain Res 129:152–157CrossRefPubMedGoogle Scholar
  24. Illig KR, Haberly LB (2003) Odor-evoked activity is spatially distributed in piriform cortex. J Comp Neurol 457:361–373. doi: 10.1002/cne.10557 CrossRefPubMedGoogle Scholar
  25. Jang D-P, Lee S-H, Lee S-Y et al (2009) Neural responses of rats in the forced swimming test: [F-18]FDG micro PET study. Behav Brain Res 203:43–47. doi: 10.1016/j.bbr.2009.04.020 CrossRefPubMedGoogle Scholar
  26. Johnson BA, Leon M (2007) Chemotopic odorant coding in a mammalian olfactory system. J Comp Neurol 503:1–34. doi: 10.1002/cne.21396 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Jourdan F, Duveau A, Astic L, Holley A (1980) Spatial distribution of [14C]-2-deoxyglucose uptake in the olfactory bulbs of rats stimulated with two different odours. Brain Res 188:139–154CrossRefPubMedGoogle Scholar
  28. Kida I, Xu F, Shulman RG, Hyder F (2002) Mapping at glomerular resolution: fMRI of rat olfactory bulb. Magn Reson Med 48:570–576. doi: 10.1002/mrm.10248 CrossRefPubMedGoogle Scholar
  29. Lancelot S, Zimmer L (2010) Small-animal positron emission tomography as a tool for neuropharmacology. Trends Pharmacol Sci 31:411–417. doi: 10.1016/j.tips.2010.06.002 CrossRefPubMedGoogle Scholar
  30. Lancelot S, Roche R, Slimen A et al (2014) A multi-atlas based method for automated anatomical rat brain MRI segmentation and extraction of PET activity. PLoS One 9:e109113. doi: 10.1371/journal.pone.0109113 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Litaudon P, Cattarelli M (1994) Multisite recordings of the brain in the in vivo rat using a voltage-sensitive dye. Neurosci Prot 070–02:1–15Google Scholar
  32. Litaudon P, Datiche F, Cattarelli M (1997a) Optical recording of the rat piriform cortex activity. Prog Neurobiol 52:485–510CrossRefPubMedGoogle Scholar
  33. Litaudon P, Mouly A-M, Sullivan R et al (1997b) Learning-induced changes in rat piriform cortex mapped using multisite recording with voltage-sensitive dye. Eur J Neurosci 8:1593–1602CrossRefGoogle Scholar
  34. Litaudon P, Amat C, Bertrand B et al (2003) Piriform cortex functional heterogeneity revealed by cellular responses to odours. Eur J Neurosci 17:2457–2461. doi: 10.1046/j.1460-9568.2003.02654.x CrossRefPubMedGoogle Scholar
  35. Litaudon P, Garcia S, Buonviso N (2008) Strong coupling between pyramidal cell activity and network oscillations in the olfactory cortex. Neuroscience 156:781–787CrossRefPubMedGoogle Scholar
  36. Luyten L, Casteels C, Vansteenwegen D et al (2012) Micro-positron emission tomography imaging of rat brain metabolism during expression of contextual conditioning. J Neurosci 32:254–263. doi: 10.1523/JNEUROSCI.3701-11.2012 CrossRefPubMedGoogle Scholar
  37. Martin C, Grenier D, Thévenet M et al (2007) fMRI visualization of transient activations in the rat olfactory bulb using short odor stimulations. Neuroimage 36:1288–1293. doi: 10.1016/j.neuroimage.2007.04.029 CrossRefPubMedGoogle Scholar
  38. Miyamichi K, Amat F, Moussavi F et al (2011) Cortical representations of olfactory input by trans-synaptic tracing. Nature 472:191–196. doi: 10.1038/nature09714 CrossRefPubMedGoogle Scholar
  39. Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates. Elsevier Academic Press, SidneyGoogle Scholar
  40. Poo C, Isaacson JS (2009) Odor representations in olfactory cortex: “sparse” coding, global inhibition, and oscillations. Neuron 62:850–861. doi: 10.1016/j.neuron.2009.05.022 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Rampin O, Bellier C, Maurin Y (2012) Electrophysiological responses of rat olfactory tubercle neurons to biologically relevant odours. Eur J Neurosci 35:97–105. doi: 10.1111/j.1460-9568.2011.07940.x CrossRefPubMedGoogle Scholar
  42. Ravasi L, Shimoji K, Soto-Montenegro ML et al (2011) Use of [18F]fluorodeoxyglucose and the ATLAS small animal PET scanner to examine cerebral functional activation by whisker stimulation in unanesthetized rats. Nucl Med Commun 32:336–342. doi: 10.1097/MNM.0b013e3283447292 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Rennaker RL, Chen CF, Ruyle AM et al (2007) Spatial and temporal distribution of odorant-evoked activity in the piriform cortex. J Neurosci 27:1534–1542. doi: 10.1523/JNEUROSCI.4072-06.2007 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Royet J-P, Plailly J (2004) Lateralization of olfactory processes. Chem Senses 29:731–745. doi: 10.1093/chemse/bjh067 CrossRefPubMedGoogle Scholar
  45. Scalia F, Winans SS (1975) The differential projections of the olfactory bulb and accessory olfactory bulb in mammals. J Comp Neurol 161:31–55. doi: 10.1002/cne.901610105 CrossRefPubMedGoogle Scholar
  46. Schoenbaum G, Eichenbaum H (1995) Information coding in the rodent prefrontal cortex.1. Single-neuron activity in orbitofrontal cortex compared with that in pyriform cortex. J Neurophysiol 74:733–750PubMedGoogle Scholar
  47. Schwob JE, Price JL (1978) The cortical projections of the olfactory bulb: development in fetal and neonatal rats with additional observations in the adult. Brain Res 151:369–374CrossRefPubMedGoogle Scholar
  48. Sharp FR, Gonzalez MF (1985) Multiple vibrissae sensory regions in rat cerebellum: a (14C) 2-deoxyglucose study. J Comp Neurol 234:489–500. doi: 10.1002/cne.902340407 CrossRefPubMedGoogle Scholar
  49. Sharp FR, Kauer JS, Shepherd GM (1975) Local sites of activity-related glucose metabolism in rat olfactory bulb during olfactory stimulation. Brain Res 98:596–600CrossRefPubMedGoogle Scholar
  50. Sharp FR, Gonzalez MF, Sharp JW, Sagar SM (1989) c-fos expression and (14C) 2-deoxyglucose uptake in the caudal cerebellum of the rat during motor/sensory cortex stimulation. J Comp Neurol 284:621–636. doi: 10.1002/cne.902840409 CrossRefPubMedGoogle Scholar
  51. Sobel N, Prabhakaran V, Desmond JE et al (1998a) Sniffing and smelling: separate subsystems in the human olfactory cortex. Nature 392:282–286. doi: 10.1038/32654 CrossRefPubMedGoogle Scholar
  52. Sobel N, Prabhakaran V, Hartley CA et al (1998b) Odorant-induced and sniff-induced activation in the cerebellum of the human. J Neurosci 18:8990–9001PubMedGoogle Scholar
  53. Sobel N, Prabhakaran V, Zhao Z et al (2000) Time course of odorant-induced activation in the human primary olfactory cortex. J Neurophysiol 83:537–551PubMedGoogle Scholar
  54. Sosulski DL, Bloom ML, Cutforth T et al (2011) Distinct representations of olfactory information in different cortical centres. Nature 472:213–216. doi: 10.1038/nature09868 CrossRefPubMedPubMedCentralGoogle Scholar
  55. Soto-Montenegro ML, Vaquero JJ, Pascau J et al (2009) Detection of visual activation in the rat brain using 2-deoxy-2-[(18)F]fluoro-d-glucose and statistical parametric mapping (SPM). Mol Imaging Biol 11:94–99. doi: 10.1007/s11307-008-0179-7 CrossRefPubMedGoogle Scholar
  56. Sung K-K, Jang D-P, Lee S et al (2009) Neural responses in rat brain during acute immobilization stress: a [F-18]FDG micro PET imaging study. NeuroImage 44:1074–1080. doi: 10.1016/j.neuroimage.2008.09.032 CrossRefPubMedGoogle Scholar
  57. Takahashi YK, Kurosaki M, Hirono S, Mori K (2004) Topographic representation of odorant molecular features in the rat olfactory bulb. J Neurophysiol 92:2413–2427. doi: 10.1152/jn.00236.2004 CrossRefPubMedGoogle Scholar
  58. Torquet N, Aimé P, Messaoudi B et al (2014) Olfactory preference conditioning changes the reward value of reinforced and non-reinforced odors. Front Behav Neurosci 8:229. doi: 10.3389/fnbeh.2014.00229 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Veyrac A, Allerborn M, Gros A et al (2015) Memory of occasional events in rats: individual episodic memory profiles, flexibility, and neural substrate. J Neurosci 35:7575–7586. doi: 10.1523/JNEUROSCI.3941-14.2015 CrossRefPubMedGoogle Scholar
  60. Welker WI (1964) Analysis of sniffing of the albino rat. Behavior 22:223–244CrossRefGoogle Scholar
  61. Xu W, Wilson DA (2012) Odor-evoked activity in the mouse lateral entorhinal cortex. Neuroscience 223:12–20. doi: 10.1016/j.neuroscience.2012.07.067 CrossRefPubMedPubMedCentralGoogle Scholar
  62. Xu F, Kida I, Hyder F, Shulman RG (2000) Assessment and discrimination of odor stimuli in rat olfactory bulb by dynamic functional MRI. Proc Nat Acad Sci USA 19:10601–10606. doi: 10.1073/pnas.180321397 CrossRefGoogle Scholar
  63. Xu F, Liu N, Kida I et al (2003) Odor maps of aldehydes and esters revealed by functional MRI in the glomerular layer of the mouse olfactory bulb. Proc Natl Acad Sci USA 100:11029–11034. doi: 10.1073/pnas.1832864100 CrossRefPubMedPubMedCentralGoogle Scholar
  64. Yang X, Renken R, Hyder F et al (1998) Dynamic mapping at the laminar level of odor-elicited responses in rat olfactory bulb by functional MRI. Proc Nat Acad Sci USA 95:7715–7720CrossRefPubMedPubMedCentralGoogle Scholar
  65. Zhan C, Luo M (2010) Diverse patterns of odor representation by neurons in the anterior piriform cortex of awake mice. J Neurosci 30:16662–16672. doi: 10.1523/JNEUROSCI.4400-10.2010 CrossRefPubMedGoogle Scholar
  66. Zinyuk LE, Datiche F, Cattarelli M (2001) Cell activity in the anterior piriform cortex during an olfactory learning in the rat. Behav Brain Res 124:29–32CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Philippe Litaudon
    • 1
  • Caroline Bouillot
    • 2
  • Luc Zimmer
    • 2
    • 3
    • 4
  • Nicolas Costes
    • 2
  • Nadine Ravel
    • 1
  1. 1.Lyon Neuroscience Research Center, Olfaction: from coding to memory TeamCNRS UMR 5292, INSERM U1028, Université Claude Bernard Lyon 1Lyon CedexFrance
  2. 2.CERMEP-Imagerie du VivantBronFrance
  3. 3.Hospices Civils de LyonLyonFrance
  4. 4.Lyon Neuroscience Research Center, Radiopharmaceutical and Neurochemical Biomarkers TeamCNRS UMR 5292, INSERM U1028, Université Claude Bernard Lyon 1BRON CedexFrance

Personalised recommendations