Genetic influences of autism candidate genes on circuit wiring and olfactory decoding

Abstract

Olfaction supports a multitude of behaviors vital for social communication and interactions between conspecifics. Intact sensory processing is contingent upon proper circuit wiring. Disturbances in genetic factors controlling circuit assembly and synaptic wiring can lead to neurodevelopmental disorders, such as autism spectrum disorder (ASD), where impaired social interactions and communication are core symptoms. The variability in behavioral phenotype expression is also contingent upon the role environmental factors play in defining genetic expression. Considering the prevailing clinical diagnosis of ASD, research on therapeutic targets for autism is essential. Behavioral impairments may be identified along a range of increasingly complex social tasks. Hence, the assessment of social behavior and communication is progressing towards more ethologically relevant tasks. Garnering a more accurate understanding of social processing deficits in the sensory domain may greatly contribute to the development of therapeutic targets. With that framework, studies have found a viable link between social behaviors, circuit wiring, and altered neuronal coding related to the processing of salient social stimuli. Here, the relationship between social odor processing in rodents and humans is examined in the context of health and ASD, with special consideration for how genetic expression and neuronal connectivity may regulate behavioral phenotypes.

Tackling hypo and hyper sensory processing heterogeneity in autism: From clinical stratification to genetic pathways

“…Individuals with a high dSSP score, that is, those with an excess of hyper-sensory processing sensitivities, displayed a significant trend for the enrichment of deleterious gene mutations in the GABAergic pathway. Our results were in accordance with numerous reports describing the association between genes affecting directly (such as GABRA4, GRIN1) or indirectly (such CACNA1C, SHANK1-3, CNTN3-6) the GABAergic pathway homeostasis and sensory processing divergences in autism spectrum (Hartig et al, 2021;Leblond et al, 2014;Mercati et al, 2017;Tavassoli et al, 2021). The excess load of deleterious mutations affecting the genes of GABAergic pathway reported in our study may reduce the GABAergic tone (Ferguson & Gao, 2018)-as previously showed (Sapey-Triomphe et al, 2019)-and may explain the hypersensitivity observed in autism spectrum.…”

Hypo- and hyper- sensory processing heterogeneity in Autism Spectrum Disorder

“…We speci cally observed mutations affecting the genes as GABARAPL1, GABBR2,…(Supplementary Table 2). Our results were in accordance with numerous reports describing the association between genes affecting directly (such as GABRA4, GRIN1) or indirectly (such CACNA1C, SHANK1-3, CNTN3-6) the GABAergic pathway homeostasis and sensory processing atypicalities in ASD (Leblond et al, 2014;Mercati et al, 2017;Tavassoli et al, 2021, Hartig et al, 2021. The excess load of deleterious mutations affecting the genes of GABAergic pathway reported in our study may reduce the GABAergic tone (Ferguson and Gao, 2018) -as previously showed (Sapey-Triomphe et al, 2019) -and may explained the hypersensitivity observed in ASD.…”

Editorial for the special issue "Olfactory Coding and Circuitries"

“…The causes and consequences of a disruption of the human sense of smell and currently available treatments of olfactory dysfunction are reviewed by Schäfer et al (2021). The last review of this series deals with genetic influence of autism candidate genes on circuit wiring and olfactory decoding (Hartig et al 2021). This review in detail examines the relationship between social odor processing in humans and rodents in the context of health and autism spectrum disorder.…”