A systematic-review of olfactory deficits in neurodevelopmental disorders: From mouse to human

Abstract

Olfactory impairment is a common clinical motif across neurodevelopmental disorders, suggesting olfactory circuits are particularly vulnerable to disease processes and can provide insight into underlying disease mechanisms. The mouse olfactory bulb is an ideal model system to study mechanisms of neurodevelopmental disease due to its anatomical accessibility, behavioral relevance, ease of measuring circuit input and output, and the feature of adult neurogenesis. Despite the clinical relevance and experimental benefits, olfactory testing across animal models of neurodevelopmental disease has been inconsistent and non-standardized. Here we performed a systematic literature review of olfactory function testing in mouse models of neurodevelopmental disorders, and identified intriguing inconsistencies that include evidence for both increased and decreased acuity in odor detection in various mouse models of Autism Spectrum Disorder (ASD). Based on our identified gaps in the literature, we recommend direct comparison of different mouse models of ASD using standardized tests for odor detection and discrimination. This review provides a framework to guide future olfactory function testing in mouse models of neurodevelopmental diseases.

Keywords: Anosmia; Hyposmia; Mouse models of neurological disease; Neurodevelopmental disorders; Olfaction; Sensory circuits.

Figure 1

Flowsheet of systematic literature review.

Figure 2. Olfactory bulb development and local circuitry.

A) Timeline of olfactory bulb development. B) View of whole mouse brain. Olfactory bulbs are labeled and coronal section of mouse olfactory bulb highlighting different layers and local circuitry. E-embryonic day, MC-mitral cells, LOT-lateral olfactory tract, GC-granule cells, GL-glomerular layer, PGC-periglomerular cells.

Figure 3. Olfactory skill testing in mice and humans.

Figure shows the different types of olfactory tests in mice and humans for each testable olfactory skill. Note that for humans, the Sniffin’ sticks test evaluates olfactory sensitivity, discrimination, and identification. In the mouse, each olfactory skill is evaluated by different types of tests. There is no test for olfactory preference in the human. UPSIT-University of Pennsylvania Smell Identification Test. BSIT – Brief Smell Identification Test