Long-term olfactory enrichment promotes non-olfactory cognition, noradrenergic plasticity and remodeling of brain functional connectivity in older mice.

Brain functional and structural changes lead to cognitive decline during aging, but a high level of cognitive stimulation during life can improve cognitive performances in the older adults, forming the cognitive reserve. Noradrenaline has been proposed as a molecular link between environmental stimulation and constitution of the cognitive reserve. Taking advantage of the ability of olfactory stimulation to activate noradrenergic neurons of the locus coeruleus, we used repeated olfactory enrichment sessions over the mouse lifespan to enable the cognitive reserve buildup. Mice submitted to olfactory enrichment, whether started in early or late adulthood, displayed improved olfactory discrimination at late ages and interestingly, improved spatial memory and cognitive flexibility. Moreover, olfactory and non-olfactory cognitive performances correlated with increased noradrenergic innervation in the olfactory bulb and dorsal hippocampus. Finally, c-Fos mapping and connectivity analysis revealed task-specific remodeling of functional neural networks in enriched older mice. Long-term olfactory enrichment thus triggers structural noradrenergic plasticity and network remodeling associated with better cognitive aging and thereby forms a promising mouse model of the cognitive reserve buildup.

Lessons from behavioral lateralization in olfaction.

Sensory information, sampled by sensory organs positioned on each side of the body may play a crucial role in organizing brain lateralization. This question is of particular interest with regard to the growing evidence of alteration in lateralization in several psychiatric conditions. In this context, the olfactory system, an ancient, mostly ipsilateral and well-conserved system across phylogeny may prove an interesting model system to understand the behavioral significance of brain lateralization. Here, we focused on behavioral data in vertebrates and non-vertebrates, suggesting that the two hemispheres of the brain differentially processed olfactory cues to achieve diverse sensory operations, such as detection, discrimination, identification of behavioral valuable cues or learning. These include reports across different species on best performances with one nostril or the other or odorant active sampling by one nostril or the other, depending on odorants or contexts. In some species, hints from peripheral anatomical or functional asymmetry were proposed to explain these asymmetries in behavior. Instigations of brain activation or more rarely of brain connectivity evoked by odorants revealed a complex picture with regards to asymmetric patterns which is discussed with respect to behavioral data. Along the steps of the discussed literature, we propose avenues for future research.

Short-term availability of adult-born neurons for memory encoding.

Adult olfactory neurogenesis provides waves of new neurons involved in memory encoding. However, how the olfactory bulb deals with neuronal renewal to ensure the persistence of pertinent memories and the flexibility to integrate new events remains unanswered. To address this issue, mice performed two successive olfactory discrimination learning tasks with varying times between tasks. We show that with a short time between tasks, adult-born neurons supporting the first learning task appear to be highly sensitive to interference. Furthermore, targeting these neurons using selective light-induced inhibition altered memory of this first task without affecting that of the second, suggesting that neurons in their critical period of integration may only support one memory trace. A longer period between the two tasks allowed for an increased resilience to interference. Hence, newly formed adult-born neurons regulate the transience or persistence of a memory as a function of information relevance and retrograde interference.

Non-imaged based method for matching brains in a common anatomical space for cellular imagery.

BACKGROUND: Cellular imagery using histology sections is one of the most common techniques used in Neuroscience. However, this inescapable technique has severe limitations due to the need to delineate regions of interest on each brain, which is time consuming and variable across experimenters. NEW METHOD: We developed algorithms based on a vectors field elastic registration allowing fast, automatic realignment of experimental brain sections and associated labeling in a brain atlas with high accuracy and in a streamlined way. Thereby, brain areas of interest can be finely identified without outlining them and different experimental groups can be easily analyzed using conventional tools. This method directly readjusts labeling in the brain atlas without any intermediate manipulation of images. RESULTS: We mapped the expression of cFos, in the mouse brain (C57Bl/6J) after olfactory stimulation or a non-stimulated control condition and found an increased density of cFos-positive cells in the primary olfactory cortex but not in non-olfactory areas of the odor-stimulated animals compared to the controls. COMPARISON WITH EXISTING METHOD(S): Existing methods of matching are based on image registration which often requires expensive material (two-photon tomography mapping or imaging with iDISCO) or are less accurate since they are based on mutual information contained in the images. Our new method is non-imaged based and relies only on the positions of detected labeling and the external contours of sections. CONCLUSIONS: We thus provide a new method that permits automated matching of histology sections of experimental brains with a brain reference atlas.