Zinc-induced peripheral anosmia and behavioral responses to novelty in mice: A quantitative-genetic analysis

doi:10.1016/S0163-1047(87)90589-9

Behavioral and Neural Biology

Volume 48, Issue 1, July 1987, Pages 63-82

https://doi.org/10.1016/S0163-1047(87)90589-9 Get rights and content

Adult male mice were made anosmic by intranasal flushing with a 5% zinc sulfate solution. Twelve behavioral variables were measured in treated as well as saline-irrigated control animals placed in a novel environment. The genetic underpinnings and the genotype—treatment interactions with regard to these behaviors were analyzed in a classical Mendelian cross between the inbred strains C57BL/6 and DBA/2 and in a full 4 × 4 diallel cross, replicated five times, between these strains and strains C3H/St an CPB-K. Based on the hypothesis of an evolutionary history of directional selection for a well-balanced information-processing system, one might expect directional dominance for decrease in exploration after anosmization. Although decreases were found for several behavioral phenotypes, only few and relatively unimportant genotype—treatment interactions were present. This absence of any kind of genetic variation for behavioral change after anosmization points to an extremely strong directional selection which has eliminated all less favorable alleles. The findings support the hypothesis of directional selection for an efficient olfactory information-processing system.

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Additionally, experiments with anosmic mice (lacking sense of smell) have shown that the presence of sensory afferentation is critical for granule cells to survive between 15 and 45 days and even later after birth (Mandairon et al., 2003; Petreanu and Alvarez-Buylla, 2002). [ Technically, anosmic mice can be obtained either by targeted mutations (McEwen et al., 2007; Belluscio et al., 1998) or by destroying olfactory receptor cells with zinc sulfate solution (Crusio and van Abeelen, 1987; Andiné et al., 1995; Uebayashi et al., 2001; McBride et al., 2003)]. Different molecules, including both growth and trophic factors, are also important for insertion of new cells into existing networks (Kuhn et al., 2005).
The outpost position of the olfactory bulb (OB) between the direct inputs from sensory neurons of the nasal epithelium and other parts of the brain suggests its highest vulnerability among all brain structures to penetration of exogenous agents. A number of neurotropic viruses have been found to invade the brain through the OB. There is growing evidence that microscopic particles of toxic dusts can propagate from the nasal epithelium to the OB and further into the brain. These harmful agents impair cellular elements of the brain. Apparently, cells in the OB are the most affected, as they are the first to encounter viral infections and toxic particles. It is well known that neuronal and glial progenitors are continuously generated from neuronal stem cells in the subventricular zone of the adult brain and then migrate predominantly into the OB. Therefore, it is feasible to suggest that substitution of injured or dead cells in the OB by new-born neurons, differentiating from progenitors, plays a role in protecting the OB neuronal microcircuits from destruction. Furthermore, some cytokines and chemokines released in response to infection and/or intoxication can modulate different stages of neurogenesis (proliferation, migration, and differentiation). We hypothesize that continuous neurogenesis in the olfactory system throughout adulthood evolved as a protective mechanism to prevent impairment of the most ancient but vitally important sensory system. In addition, differentiation of a substantial portion of progenitors to glial cells, including macrophages and microglia, may create an additional barrier to exogenous agents on their way deep to the brain.
Effects of intranasal ZnSO<inf>4</inf> irrigation on olfactory and trigeminal cues
1994, Physiology and Behavior
Intranasal irrigation with ZnSO₄ solutions is used for experimental induction of anosmia. It is, however, unknown whether the trigeminal nerve is affected by the treatment. One day after irrigation (concentrations investigated were between 0.05–1%) the ability of food finding, an olfactory cue, was decreased in a concentration-dependent manner. The trigeminal effect was investigated from a reflexively induced decrease in respiratory rate due to n-propanol exposure. No impairment occurred at 1% ZnSO₄. Anosmia was also seen 2–3 h after an irrigation with solutions of 0.05–1% ZnSO₄. At the same time, 0.2 and 1% solutions in themselves decreased the respiratory rate due to reflexes from the upper and lower respiratory tract. A conspicuous systemic effect can be ruled out as the Zn⁺⁺ antidote, CaNa₂EDTA, had no effect on the decrease. A direct activation of the trigeminal nerve due to a reaction with a thiol group may explain the effect from the upper airways.
Genetic analysis of isolation-induced aggression in the mouse. III. Classical cross-breeding analysis of differences between two closely related inbred strains
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In two preceding papers we reported on two closely related inbred mouse strains, ABG and AB//Halle that display very large differences in isolation-induced intermale aggression. In the present article we investigated animals from a complete Mendelian cross between these strains to test the hypothesis that the behavioral difference is due to genetic variation at only a few loci, possibly only one. In the quantitative—genetic analysis of generation means and variances for the behavioral variables analyzed, relatively simple models were found. As epistasis was present in some cases, the monogenic hypothesis could not be confirmed. Also, the analysis of the segregating generations by means of Collins' nonparametric method revealed significant deviations of observed from expected distributions. We conclude that differences at more than only one single locus are correlated with the behavioral difference.
Peripheral olfactory deafferentation of the primary olfactory system in rats using ZnSO<inf>4</inf> nasal spray with special reference to maternal behavior
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A modified method of applying ZnSO₄ to the olfactory mucosa is described. Treated rats experienced severe nasal congestion that cleared within 24 h; more persistent morbidity did not occur. Nonpregnant females observed with male intruders 24 h following ZnSO₄ showed no alterations in behavior other than a reduction in anogenital sniffing, indicating that they were not hypoactive or irritable. In other experiments, lactating females were observed in a hole-board apparatus; 2 days posttreatment anosmia was confirmed in 80% of bilaterally ZnSO₄-treated females by the absence of preference for pup odors. After bilateral but not unilateral ZnSO₄ treatment, initially activity scores and nose pokes were equivalent in all groups, but later they both were lower than in controls, probably due to a more rapid habituation to the novel apparatus. We conclude that intranasal ZnSO₄ by small-volume spray is a useful experimental tool.
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Does intranasal application of zinc sulfate produce anosmia in the mouse? An olfactometric and anatomical study
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¹: We thank Anne K. Kremer (Utrecht) for kindly providing breeders of strain CPB-K; Dr. J.M.L. Kerbusch (Nijmegen) for advice and for the computer program of his modelsearching procedure; Mr. W. H. Doesburg and Mr. W.A.J.G. Lemmens (Nijmegen) for their statistical advice concerning the allocation procedure; Anton Buis and Ron Engels for their skillful biotechnical assistance; Professor A.P. van Overbeeke for reading an earlier version of the manuscript; and two anonymous reviewers for their very useful comments.

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Zinc-induced peripheral anosmia and behavioral responses to novelty in mice: A quantitative-genetic analysis

Physiology and Behavior

Neurosciences and Biobehavioral Reviews

Physiology and Behavior

Physiology and Behavior

Animal behavior: An evolutionary approach

What genetical architecture can tell us about the natural selection of behavioural traits

A quantitative-genetic analysis of hippocampal variation in the mouse

Journal of Neurogenetics

The replicated diallel cross: A generalized method of analysis

Behavior Genetics

The genetic architecture of behavioural responses to novelty in mice

Heredity