Olfactory bulb removal and its effects on reproduction in rodents

1. Olfactory bulb removal and its effects on reproduction in rodents Andrew Clark Eco/Evo 208 November 10, 2004

2. A review of past experiments • Brunjes, P. C. 1992. Lesson from lesions: the effects of olfactory bulbectomy. Chemical Senses. 17: 729-763. • Included 406 citations

3. Olfactory Bulbectomy • Studies include effects on: • anosmia • hormones • circadian rhythms • aggression • activity • learning • development • maternal behavior • thermoregulation • heart rate • sexual behavior & physiology (Brunjes, 1992)

4. Ideal Surgical & Experimental Procedures • Pretest: to determine if subjects are sexually competent. • Surgery: • Bulbectomy (exposure and aspiration of olfactory bulb) • Sham Operation (exposure of bulbs alone) • Experiments • Euthanization of bulbectomized individuals for histological data • bulbs may be partially removed

5. Problems with some past studies • Explaining effects of bulbectomy should not be based on anosmia alone • Clear description of surgical methods lacking • Few histological data from post-mortem examinations • Partial removal of olfactory bulb might have presented inadequate results • bulb remnants may be sufficient enough to maintain olfaction (Brunjes, 1992)

6. Specific References • Donovan, B. T. & P. C. Kopriva. 1965. Effect of removal or stimulation of the olfactory bulbs on the estrous cycle of the Guinea pig. Endocrinology. 77: 213-217. • Horton, L. W. & B. A. Shepherd. 1979. Effects of olfactory bulb ablation on estrus-induction and frequency of pregnancy. Physiology & Behavior. 22: 847-850. • Lumia, A. R., Zebrowski, A. F., & M. Y. McGinnis. 1987. Olfactory bulb removal decreases androgen receptor binding in amygdala and hypothalamus and disrupts masculine sexual behavior. Brain Research. 404: 121-126.

7. Overall Hypothesis • Removal and/or stimulation of the olfactory bulbs in mammals (Rodenta) will induce changes in their reproductive physiology, which in turn will decrease reproductive activity.

8. Introduction (Donovan & Kopriva, 1965) • Subject: the Guinea pig • inspired by a previous experiment on bulbectomy in the pig • similar sexual cycles to the pig • Purpose: • to determine the effect of removal and electrical stimuli of olfactory bulbs on reproduction in the guinea pig

9. Methods (Donovan & Kopriva, 1965) • Bulbectomized Guinea Pigs • cycle lengths compared with normal females • estrus determined by vaginal smears (% cornified cells) • mating frequencies compared with normal females • Electrically Stimulated Guinea Pigs • no bulbectomies • cycle lengths compared with non-stimulated Guinea pigs

10. Results (Donovan & Kopriva, 1965) • Bulbectomized Guinea Pigs: • No significant difference in cycle lengths between experimental & control groups. • Significant difference in mating occurrences between experimental & control groups. • However pregnancy and delivery were normal for experimental guinea pigs that mated

11. Results (Donovan & Kopriva, 1965) • Electrically Stimulated Guinea Pigs: • No significant difference in cycle lengths between electrically stimulated groups and control groups

12. Conclusions (Donovan & Kopriva, 1965) • Olfactory bulbs • not needed for estrus cycling in the Guinea pig • contradicts findings from earlier experiment on the pig • could be necessary for inducing mating behaviors

13. Introduction (Horton & Shepherd, 1978) • Subject: the Prairie vole (Microtus ochrogaster ochrogaster). • Reflex ovulators • estrus in females induced by male odors • Hypothesis: • estrus induction in M. o. ochrgaster is dependent on intact olfactory bulbs.

14. Methods (Horton & Shepherd, 1978) • Groups under study: • Intact (IC) • Sham-operated (SC) • Partially bulbectomized (PB) • Completely bulbectomized (CB) • Estrus cycling indicated by lordosis

15. Results (Horton & Shepherd, 1978) • No significant differences: • in lordosis and pregnancy between IC and SC • in lordosis and pregnancy between PB and SC • Significant reduction in lordosis and pregnancy: • CB vs IC, CB vs SC, and CB vs PB

16. Conclusions (Horton & Shepherd, 1978) • Estrus induction in M. o. ochrogaster depends on olfactory stimuli • Still in question: • 4 pregnant CB females that did not show lordosis • the effects of partial bulbectomy

17. Introduction (Lumia et al., 1987) • Subject: male rats • Hypothesis: • Bulbectomy will reduce androgen receptor levels in limbic structures: • amygdala • hypothalamus • preoptic area • septum • Decreased androgen receptor binding will be correlated with reduced masculine copulatory behavior

18. Methods (Lumia et al., 1987) • 2 groups of sexually experienced male rats: • Bulbectomized • Sham operated • Measured: • copulatory behavior (achieving > 2 ejaculations) • concentrations of cell nuclear androgen binding in limbic structures

19. Results (Lumia et al., 1987) • Bulbectomy significantly reduced percentage of sexually experienced males that achieved ejaculation • * = P < 0.007 • ** = P < 0.009 • *** = P < 0.001 • **** = P < 0.004

20. Results (Lumia et al., 1987) • Bulbectomy significantly reduced concentrations of androgen-receptor binding in amygdala and hypothalamus • * = P < 0.05 • ** = P < 0.025

21. Conclusion (Lumia et al., 1987) • Olfactory and limbic structures • important in modulating androgen receptor interactions • Bulbectomy • reduces androgen receptor binding • impairs sexual behavior in male rats

22. Overall Conclusions • Female Rodents • Olfactory Bulbs • needed for estrus cycling and mating behavior • importance may vary between species of rodents • Male Rodents • Olfactory Bulbs and Limbic Structures • needed for androgen-binding at receptors • affects mating behavior

23. Questions & Comments?