Study of the neuronal response to olfactory stimuli in control and LPS-stimulated mice by functional magnetic resonance imaging. A. E. Akulov, A. V. Romashchenko, O. B. Shevelev, D. V. Petrovski, A. A. Savelov, M. P. Moshkin


Olfactory perception plays the key role in the inter­action of animals with biotic factors of the species-specific econiche. Identification of odorants informs nocturnal animals about social environment, presence of predators, or infected food. Olfactory efficiency depends on physiological conditions; in particular, odor sensitivity can be changed by infection. This work considers use of fMRI in the study of the influence of innate immunity activation on neuronal response during perception and differentiation of socially significant (2.5-dimethylpyrazine, 2-heptanon) and socially insignificant (1-hexanol and isoprene) olfactory stimuli by CD-1 mice. We stimulated innate immunity by intraperitoneal injection of bacterial lipopolysaccharide (LPS) at the dose 500 µg/kg three hours before tomography. Urethane anesthesia was used during MRI trail. Odor stimulation was done with a lab-made metering unit for supplying standard doses of volatile organic compounds. The supply of olfactory stimuli induced activation of neurons in the primary perceptual center and the centers of secondary processing of olfactory information. Olfactory stimulus type affected neuronal response rate in an olfactory bulb but did not affect response parameters in other brain regions studied. This increase in neuronal activity is likely to be of adaptive significance as a mechanism supporting olfactory sensitivity increase, which plays the key role in the identification of potential sources of infection.

About The Authors:

A. E. Akulov. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

A. V. Romashchenko. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

O. B. Shevelev. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

D. V. Petrovski. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

A. A. Savelov. International Tomography Center SB RAS, Russian Federation, Novosibirsk

M. P. Moshkin. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk


1. Andersen M.B., Zimmer J., Sams-Dodd F. Specific behavioral effects related to age and cerebral ischemia in rats. Pharmacol. Biochem. Behav. 1999;62(4):673-682.

2. Barnard S.J., Behnke J.M., Gage A.R., Brown H., Smothurst P.R. Immunity cost and behavioural modulation in male laboratory mice exposed to the odour of females. Physiol. Behav. 1997;62:857-866.

3. Bhatnagar K.P., Kennedy R.C., Baron G., Greenberg R.A. Number of mitral cells and the bulb volume in the aging human olfactory bulb: a quantitative morphological study. Anat. Rec. 1987;218(1):73-87.

4. Breder C.D., Dinarello C.A., Saper C.B. Interleukin-1 immunoreactive innervation of the human hypothalamus. Science. 1988;240:321-324.

5. Chen Y., Getchell T.V., Sparks D.L., Getchell M.L. Patterns of adrenergic and peptidergic innervation in human olfactory mucosa: agerelated trends. J. Comp. Neurol. 1993;334(1):104-116.

6. Dantzer R. Cytokine-induced sickness behavior: Where do we stand? Brain Behav. Immun. 2001;15:7-24.

7. Dong H.W. The Allen Reference Atlas: A Digital Color Brain Atlas of C57BL/6J Male Mouse. John Wiley & Sons, 2008.

8. Drickamer L.C. Urine marking and social dominance in male house mice (Mus musculus domesticus). Behav. Process. 2001;53:113-120.

9. Gibertini M., Newton C., Friedman H., Klein T.W. Spatial learning impairment in mice infected with Legionella pneumophila or administered exogenous interleukin-1-beta. Brain. Behav. Immun. 1995; 9:113-128.

10. Haehner A., Hummel T., Reichmann H. A clinical approach towards smell loss in Parkinson’s disease. J. Parkinson’s. Dis. 2014;4(2): 189-195. DOI: 10.3233/JPD-130278

11. Harrison N.A., Brydon L., Walker C., Gray M.A., Steptoe A., Critchley H.D. Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol. Psychiat. 2009a;66:407-414.

12. Harrison N.A., Brydon L., Walker C., Gray M.A., Steptoe A., Dolan R.J., Critchley H.D. Neural origins of human sickness in interoceptive responses to inflammation. Biol. Psychiat. 2009b;66:415-422.

13. Hurst J.L., Fang J., Barnard C.J. The role of substrate odours in maintaining social tolerance between male house mice, Mus musculus domesticus. Anim. Behav. 1993;45:997-1006.

14. Johnson B.A., Farahbod H., Xu Z., Saber S., Leon M. Local and global chemotopic organization: general features of the glomerular representations of aliphatic odorants differing in carbon number. J. Comp. Neurol. 2004;480:234-249.

15. Kalkonde Y.V., Shelton R., Villarreal M., Sigala G., Mishra P.K., Ahuja S.S., Barea-Rodriguez E., Moretti P., Ahuja S.K. The CC chemokine receptor 5 regulates olfactory and social recognition in mice. Neuroscience. 2011;197:153-161.

16. Kauer J.S., Moulton D.G. Responses of olfactory bulb neurons to odour stimulation of small nasal areas in the salamander. J. Physiol. 1974;243:717-737.

17. Krueger J.M., Walter J., Dinarello C.A., Wolff S.M., Chedid L. Sleeppromoting effects of endogenous pyrogen (interleukin-1). Am. J. Physiol. 1984;246:994-999.

18. Kullmann J.S., Grigoleit J.S., Wolf O.T., Engler H., Oberbeck R., Elsenbruch S., Forsting M., Schedlowski M., Gizewski E.R. Experimental human endotoxemia enhances brain activity during social cognition. Soc. Cogn. Affect Neurosci. 2014, 9(6):786-793.

19. Litvinova E.A., Goncharova E.P., Zaydman A.M., Zenkova M.A., Moshkin M.P. Female scent signals enhance the resistance of male mice to influenza. PLoS One. 2010;5(3):e9473. DOI:10.1371/journal.pone.0009473

20. Ma W., Miao Z., Novotny M.V. Role of the adrenal gland and adrenalmediated chemosignals in suppression of estrus in the house mouse: the lee-boot effect revisited. Biol. Reprod. 1998;59:1317-1320.

21. Moshkin M.P., Gerlinskaya L.A., Morozova O.V., Bakhvalova V.N., Evsikov V.I. Behaviour, chemosignals, and endocrine functions in male mice infected with tick-borne encephalitis virus. Psychoneuroendocrinology. 2002;27(5):603-608.

22. Moshkin M.P., Kolosova I.E., Novikov E.A., Litvinova E.A., Mershieva L.V., Mak V.V., Petrovskii D.V. Co-modulation of the immune function and the reproductive chemosignals. Asian-Aust. J. Anim. Sci. 2001;14:43-51.

23. Novotny M., Jemiolo B., Harvey S., Wiesler D., Marchlewska-Koj A. Adrenal-mediated endogenous metabolites inhibit puberty in female mice. Science. 1986;231:722-725.

24. Pugh C.R., Kumagawa K., Fleshner M., Watkins L.R., Maier S.F., Rudy J.W. Selective effects of peripheral lipopolysaccharide administration on contextual and auditory-cue fear conditioning. Brain Behav. Immun. 1998;12:212-229.

25. Shaw K.N., Commins S., O’Mara S.M. Lipopolysaccharide causes deficits in spatial learning in the watermaze but not in BDNF expression in the rat dentate gyrus. Behav. Brain Res. 2001;124:47-54.

26. Sultan B., May L.A., Lane A.P. The role of TNF-a in inflammatory olfactory loss. Laryngoscope. 2011;121(11):2481-2486.

27. Tirindelli R., Dibattista M., Pifferi S., Menini A. From pheromones to behavior. Physiol. Rev. 2009;89:921-956. DOI: 10.1152/physrev.00037.2008

28. Xu F., Liu N., Kida I., Rothman D.L., Hyder F., Shepherd G.M. Odor maps of aldehydes and esters revealed by functional MRI in the glomerular layer of the mouse olfactory bulb. Proc. Natl Acad. Sci. USA. 2003;100(19):11029-11034.

29. Xu F., Schaefer M., Kida I., Liu N., Rothman D.L., Hyder F., Resrtrepo D., Shepherd G.M. Simultaneous activation of mouse main and accessory olfactory bulbs by odors or pheromones. J. Comp. Neurol. 2005;489(4):491-500.

This entry was posted in Tom 19-4. Bookmark the permalink.