THALAMOCORTICAL ENCODING OF TACTILE STIMULI IN THE <EM>SHANK3 </EM>KO MOUSE MODEL OF AUTISM SPECTRUM DISORDER

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with social communication deficits, repetitive behaviors, and atypical sensory responses. Sensory abnormalities, including abnormal responses to tactile stimulation, are prevalent in 90% of individuals with ASD, but the neurobiological mechanisms underlying tactile dysfunction remain poorly understood. In this work, a combination of behavioral, histological, and electrophysiological approaches was employed to investigate tactile sensitivity and neuronal responses to glabrous skin tactile stimulation in Shank3 KO mice. Our behavioral tests show that Shank3 KO mice not only exhibit increased repetitive behaviors when exposed to a novel textured surface, but also a tendency for increased withdrawal probability when exposed to tactile stimulation on the hindpaw in the von Frey test. In addition, simultaneous in vivo electrophysiological recordings in the hindlimb region of the primary somatosensory cortex (S1HL) and the ventral posterolateral nucleus of the thalamus (VPL) show increased firing rates in both spontaneous and tactile-evoked activity of both brain regions, including across all cortical layers of the S1HL, particularly in layer 5. By providing insight into the functional alterations behind atypical touch processing in ASD, this works opens ways to the development of novel effective therapeutic strategies.