Elevated Anxiety and Impaired Attention in Super-Smeller, Kv1.3 Knockout Mice

Abstract

It has long been recognized that olfaction and emotion are linked. While chemosensory research using both human and rodent models have indicated a change in emotion can contribute to olfactory dysfunction, there are few studies addressing the contribution of olfaction to a modulation in emotion. In mice, olfactory deficits have been linked with heightened anxiety levels, suggesting that there could be an inverse relationship between olfaction and anxiety. Furthermore, increased anxiety is often co-morbid with psychiatric conditions such as attention disorders. Our study aimed to investigate the roles of olfaction in modulating anxiety. Voltage-gated potassium ion channel Kv1.3 knockout mice (Kv1.3−/−), which have heightened olfaction, and wild-type (WT) mice were examined for anxiety-like behaviors using marble burying (MB), light-dark box (LDB) and elevated-plus maze (EPM) tests. Because Kv1.3−/− mice have increased locomotor activity, inattentive and hyperactive behaviors were quantified for both genotypes. Kv1.3−/− mice showed increased anxiety levels compared to their WT counterparts and administration of methylphenidate (MPH) via oral gavage alleviated their increased anxiety. Object-based attention testing indicated young and older Kv1.3−/− mice had attention deficits and treatment with MPH also ameliorated this condition. Locomotor testing through use of a metabolic chamber indicated that Kv1.3−/− mice were not significantly hyperactive and MPH treatment failed to modify this activity. Our data suggest that heightened olfaction does not necessarily lead to decreased anxiety levels, and that Kv1.3−/− mice may have behaviors associated with inattentiveness.

Prefrontal cortex, dorsomedial striatum, and dentate gyrus are necessary in the object-based attention test in mice

“…Since its establishment, the test has become a popular method to assess attention and related underlying mechanisms in different mouse models [6][7][8]. Among many tasks that have been developed to assess attentional functions in rodents, OBAT is easy to perform and does not require expensive equipment, and therefore may be accessible to investigators on a tight budget.…”

Scorpion toxins targeting Kv1.3 channels: insights into immunosuppression

“…They had irregular intake, as well as their metabolic activities, increased locomotion during the dark cycle and behaviors similar to hyperactivity [48, 54]. Recent studies have shown that the same mice model present exacerbated behaviors related to anxiety, in addition to being inattentive [55].…”

Timely Inhibitory Circuit Formation Controlled by Abl1 Regulates Innate Olfactory Behaviors in Mouse

“…This phenotype is like the ''super-smeller mice.'' Mice with deleted voltage-gated potassium channels present in mitral cells of the OB have also shown the high olfactory sensitivity and hyperactivity (Fadool et al, 2004;Huang et al, 2018). This infers that excitatory mitral cells and inhibitory granule cells of the OB could have similar outputs in detection and sensitivity, even though they may have different molecular machineries.…”