Age-related differences in perception and coding of attractive odorants in mice.

Hedonic perception deeply changes with aging, significantly impacting health and quality of life in elderly. In young adult mice, an odor hedonic signature is represented along the antero-posterior axis of olfactory bulb, and transferred to the olfactory tubercle and ventral tegmental area, promoting approach behavior. Here, we show that while the perception of unattractive odorants was unchanged in older mice (22 months), the appreciation of some but not all attractive odorants declined. Neural activity in the olfactory bulb and tubercle of older mice was consistently altered when attraction to pleasant odorants was impaired while maintained when the odorants kept their attractivity. Finally, in a self-stimulation paradigm, optogenetic stimulation of the olfactory bulb remained rewarding in older mice even without ventral tegmental area's response to the stimulation. Aging degrades behavioral and neural responses to some pleasant odorants but rewarding properties of olfactory bulb stimulation persisted, providing new insights into developing novel olfactory training strategies to elicit motivation even when the dopaminergic system is altered as observed in normal and/or neurodegenerative aging.

Combining a Breath-Synchronized Olfactometer with Brain Simulation to Study the Impact of Odors on Corticospinal Excitability and Effective Connectivity.

It is widely accepted that olfactory stimulation elicits motor behaviors, such as approaching pleasant odorants and avoiding unpleasant ones, in animals and humans. Recently, studies using electroencephalography and transcranial magnetic stimulation (TMS) have demonstrated a strong link between processing in the olfactory system and activity in the motor cortex in humans. To better understand the interactions between the olfactory and the motor systems and to overcome some of the previous methodological limitations, we developed a new method combining an olfactometer that synchronizes the random order presentation of odorants with different hedonic values and the TMS (single- and dual-coil) triggering with nasal breathing phases. This method allows probing the modulations of corticospinal excitability and effective ipsilateral connectivity between the dorsolateral prefrontal cortex and the primary motor cortex that could occur during pleasant and unpleasant odor perception. The application of this method will allow for objectively discriminating the pleasantness value of an odorant in a given participant, indicating the biological impact of the odorant on brain effective connectivity and excitability. In addition, this could pave the way for clinical investigations in patients with neurological or neuropsychiatric disorders who may exhibit odor hedonic alterations and maladaptive approach-avoidance behaviors.

Chronic unpredictable mild stress alters odor hedonics and adult olfactory neurogenesis in mice.

Experiencing chronic stress significantly increases the risk for depression. Depression is a complex disorder with varied symptoms across patients. However, feeling of sadness and decreased motivation, and diminished feeling of pleasure (anhedonia) appear to be core to most depressive pathology. Odorants are potent signals that serve a critical role in social interactions, avoiding danger, and consummatory behaviors. Diminished quality of olfactory function is associated with negative effects on quality of life leading to and aggravating the symptoms of depression. Odor hedonic value (I like or I dislike this smell) is a dominant feature of olfaction and guides approach or avoidance behavior of the odor source. The neural representation of the hedonic value of odorants is carried by the granule cells in the olfactory bulb, which functions to modulate the cortical relay of olfactory information. The granule cells of the olfactory bulb and those of the dentate gyrus are the two major populations of cells in the adult brain with continued neurogenesis into adulthood. In hippocampus, decreased neurogenesis has been linked to development or maintenance of depression symptoms. Here, we hypothesize that chronic mild stress can alter olfactory hedonics through effects on the olfactory bulb neurogenesis, contributing to the broader anhedonia phenotype in stress-associated depression. To test this, mice were subjected to chronic unpredictable mild stress and then tested on measures of depressive-like behaviors, odor hedonics, and measures of olfactory neurogenesis. Chronic unpredictable mild stress led to a selective effect on odor hedonics, diminishing attraction to pleasant but not unpleasant odorants, an effect that was accompanied by a specific decrease in adult neurogenesis and of the percentage of adult-born cells responding to pleasant odorants in the olfactory bulb.

Relationship between depression and olfactory sensory function: a review.

Links between olfactory sensory function and effect have been well established. A robust literature exists in both humans and animals showing that disrupting olfaction sensory function can elicit disordered mood state, including serve as a model of depression. Despite this, considerably less is known regarding the directionality and neural basis of this relationship, e.g. whether disruptions in sensory function precede and contribute to altered mood or if altered mood state precipitates changes in olfactory perception. Further, the neural basis of altered olfactory function in depression remains unclear. In conjunction with clinical studies, animal models represent a valuable tool to understand the relationship between altered mood and olfactory sensory function. Here, we review the relevant literature assessing olfactory performance in depression in humans and in rodent models of depressive-like behavioral states. Rodents allow for detailed characterization of alterations in olfactory perception, manipulation of experiential events that elicit depressive-like phenotypes, and allow for interrogation of potential predictive markers of disease and the cellular basis of olfactory impairments associated with depressive-like phenotypes. We synthesize these findings to identify paths forward to investigate and understand the complex interplay between depression and olfactory sensory function.