Mechanisms of Tactile Sensory Phenotypes in Autism: Current Understanding and Future Directions for Research

Schaffler, Melanie D; Middleton, Leah J.; Abdus-Saboor, Ishmail

doi:10.1007/s11920-019-1122-0

Cited by 37 publications

(26 citation statements)

References 106 publications

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“…The sensory system is a highly conserved system on multiple levels from cell to circuit [ 102 ]. While sensory symptoms have been reported in up to 90% of autistic people, around 60% specifically show tactile sensory symptoms [ 7 ].…”

Section: From Asd Development To Windows Of Treatment Opportunitymentioning

confidence: 99%

Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder

Riemersma

Havekes

Kas

2021

Genes

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Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is characterized by differences in social interaction, repetitive behaviors, restricted interests, and sensory differences beginning early in life. Especially sensory symptoms are highly correlated with the severity of other behavioral differences. ASD is a highly heterogeneous condition on multiple levels, including clinical presentation, genetics, and developmental trajectories. Over a thousand genes have been implicated in ASD. This has facilitated the generation of more than two hundred genetic mouse models that are contributing to understanding the biological underpinnings of ASD. Since the first symptoms already arise during early life, it is especially important to identify both spatial and temporal gene functions in relation to the ASD phenotype. To further decompose the heterogeneity, ASD-related genes can be divided into different subgroups based on common functions, such as genes involved in synaptic function. Furthermore, finding common biological processes that are modulated by this subgroup of genes is essential for possible patient stratification and the development of personalized early treatments. Here, we review the current knowledge on behavioral rodent models of synaptic dysfunction by focusing on behavioral phenotypes, spatial and temporal gene function, and molecular targets that could lead to new targeted gene-based therapy.

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Section: From Asd Development To Windows Of Treatment Opportunitymentioning

confidence: 99%

Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder

Riemersma

Havekes

Kas

2021

Genes

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“…Shank2/3 expression has been described at the neuromuscular junction as well as at synapses of the superior cervical and myenteric ganglion ( Raab et al, 2010 ). Growing evidence suggests that ASD-genetic mutations also alter peripheral mechanisms that contribute to ASD-associated sensory abnormalities including tactile hypersensitivity ( Orefice et al, 2019 ; Schaffler et al, 2019 ). Peripheral GABA A receptor agonist treatment can reduce tactile over-reactivity, as well as improve anxiety behaviours, body condition, and some social impairments ( Orefice et al, 2019 ).…”

Section: Other Brain Regionsmentioning

confidence: 99%

Shankopathies in the Developing Brain in Autism Spectrum Disorders

et al. 2021

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The SHANK family of proteins play critical structural and functional roles in the postsynaptic density (PSD) at excitatory glutamatergic synapses. Through their multidomain structure they form a structural platform across the PSD for protein–protein interactions, as well as recruiting protein complexes to strengthen excitatory synaptic transmission. Mutations in SHANKs reflect their importance to synapse development and plasticity. This is evident in autism spectrum disorder (ASD), a neurodevelopmental disorder resulting in behavioural changes including repetitive behaviours, lack of sociability, sensory issues, learning, and language impairments. Human genetic studies have revealed ASD mutations commonly occur in SHANKs. Rodent models expressing these mutations display ASD behavioural impairments, and a subset of these deficits are rescued by reintroduction of Shank in adult animals, suggesting that lack of SHANK during key developmental periods can lead to permanent changes in the brain’s wiring. Here we explore the differences in synaptic function and plasticity from development onward in rodent Shank ASD models. To date the most explored brain regions, relate to the behavioural changes observed, e.g., the striatum, hippocampus, sensory, and prefrontal cortex. In addition, less-studied regions including the hypothalamus, cerebellum, and peripheral nervous system are also affected. Synaptic phenotypes include weakened but also strengthened synaptic function, with NMDA receptors commonly affected, as well as changes in the balance of excitation and inhibition especially in cortical brain circuits. The effects of shankopathies in activity-dependent brain wiring is an important target for therapeutic intervention. We therefore highlight areas of research consensus and identify remaining questions and challenges.

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“…There are several mutant mice with dilution of specific target genes associated with human ASD. Although these mouse models are mainly evaluated by abnormalities in social behavior, an increasing number of reports illustrates tactile performance and impairment in these mice (103,107).…”

Section: Impairments In Tactile Senses In Mouse Models Of Asdmentioning

confidence: 99%

From Multisensory Assessment to Functional Interpretation of Social Behavioral Phenotype in Transgenic Mouse Models for Autism Spectrum Disorders

Arakawa

2020

Front. Psychiatry

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Autism spectrum disorder (ASD) is a common heterogeneous disorder, defined solely by the core behavioral characteristics, including impaired social interaction and restricted and repeated behavior. Although an increasing number of studies have been performed extensively, the neurobiological mechanisms underlying the core symptoms of ASD remain largely unknown. Transgenic mouse models provide a useful tool for evaluating genetic and neuronal mechanisms underlying ASD pathology, which are prerequisites for validating behavioral phenotypes that mimic the core symptoms of human ASD. The purpose of this review is to propose a better strategy for analyzing and interpreting social investigatory behaviors in transgenic mouse models of ASD. Mice are nocturnal, and employ multimodal processing mechanisms for social communicative behaviors, including those that involve olfactory and tactile senses. Most behavioral paradigms that have been developed for measuring a particular ASD-like behavior in mouse models, such as social recognition, preference, and discrimination tests, are based on the evaluation of distance-based investigatory behavior in response to social stimuli. This investigatory behavior in mice is regulated by multimodal processing involving with two different motives: first, an olfactory-based novelty assessment, and second, tactile-based social contact, in a temporally sequential manner. Accurate interpretation of investigatory behavior exhibited by test mice can be achieved by functional analysis of these multimodal, sequential behaviors, which will lead to a better understanding of the specific features of social deficits associated with ASD in transgenic mouse models, at high temporal and spatial resolutions.

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Mechanisms of Tactile Sensory Phenotypes in Autism: Current Understanding and Future Directions for Research

Cited by 37 publications

References 106 publications

Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder

Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder

Shankopathies in the Developing Brain in Autism Spectrum Disorders

From Multisensory Assessment to Functional Interpretation of Social Behavioral Phenotype in Transgenic Mouse Models for Autism Spectrum Disorders

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