Sensory Abnormalities in Autism Spectrum Disorders: A Focus on the Tactile Domain, From Genetic Mouse Models to the Clinic

Abstract

Sensory abnormalities are commonly recognized as diagnostic criteria in autism spectrum disorder (ASD), as reported in the last edition of the Diagnostic and Statistical Manual of Mental Disorder (DSM-V). About 90% of ASD individuals have atypical sensory experiences, described as both hyper- and hypo-reactivity, with abnormal responses to tactile stimulation representing a very frequent finding. In this review, we will address the neurobiological bases of sensory processing in ASD, with a specific focus of tactile sensitivity. In the first part, we will review the most relevant sensory abnormalities detected in ASD, and then focus on tactile processing deficits through the discussion of recent clinical and experimental studies. In the search for the neurobiological bases of ASD, several mouse models have been generated with knockout and humanized knockin mutations in many ASD-associated genes. Here, we will therefore give a brief overview of the anatomical structure of the mouse somatosensory system, and describe the somatosensory abnormalities so far reported in different mouse models of ASD. Understanding the neurobiological bases of sensory processing in ASD mouse models may represent an opportunity for a better comprehension of the mechanisms underlying sensory abnormalities, and for the development of novel effective therapeutic strategies.

Keywords: autism; behavior; mouse; somatosensory; touch.

Figure 1

The mouse somatosensory system. Somatosensory stimuli coming from the head region of the mouse are conveyed to the brain through trigeminal ganglion neurons. Neuronal fibers are depicted in blue (for trigeminal ganglion pathway) and green (for anterior and lateral spinothalamic pathways). The ophthalmic (V1), maxillary (V2) and mandibular (V3) branches of trigeminal ganglion process region-specialized somatosensory information with the maxillary branch (V2) innervating the whiskers. Here whiskers are indicated and color-coded to best follow their brain representations (whisker pad). Trigeminal ganglion neurons project to brainstem nuclei (spinal trigeminal nuclei – Sp) where they form an inverted neuronal representation of single whiskers (barrelettes). Trigeminothalamic fibers in turn project to the ventral posteromedial nucleus in the thalamus (Vpm) where again single whiskers are represented and shifted in orientation (barreloids). Finally, thalamocortical axons from the Vpm reach the primary somatosensory cortex (S1) in the barrel field, forming the final neuronal representation of single whiskers (barrels). Somatosensory stimuli coming from the body of the mouse are instead conveyed to the brainstem through dorsal root ganglia (DRG) neurons. The main difference in this system is the fact that somatosensory stimuli are conveyed to the ventral posterolateral nucleus of the thalamus (Vpl) before reaching the sensory cortex. See text for references.

Figure 2

Comparison of cortical somatosensory representation in mice and humans. Distorted representation of body areas in the mouse (A) and human (B) primary somatosensory cortex (S1). In both species, S1 somatosensory maps reflect the extent of cortical areas devoted to the processing of sensory information from different parts of the body. In mice, the altered proportions of the head and whisker pad with respect to other body regions mirrors the extent of innervation from these areas. Similarly, in humans, the cortical somatosensory representation is enlarged for those regions, such as the hands and the lips, that are densely innervated by sensory fibers. Conversely, the structure of supragranular layers 2 and 3 markedly differs between the mouse (A) and human (B) somatosensory cortex. See text for references.