Autism is a neurodevelopmental disorder, and sensorimotor disturbances are among the earliest signs of atypical development in autism, revealing themselves in early infancy. As every parent knows, infants spend most of their time asleep, and about half of that sleep time is spent in rapid eye movement (REM) sleep. One of the defining features of REM sleep is myoclonic twitching, a phenomenon which is thought to play a critical role in sensorimotor development. Twitching — jerky movements of the limbs, head, face and eyes — occurs abundantly and exclusively during REM sleep, with sensory feedback from twitching limbs acting as a primary driver of neural activity throughout the sensorimotor system. This suggests that twitching plays a role in shaping, tuning, and mapping the developing sensorimotor system and that alterations in twitching might serve as a useful model for tracking sensorimotor disturbances in autism.
Liqun Luo uses conditional, cell-type-specific RAI1 deletions in mice to assess how loss of RAI1 contributes to neurodevelopmental phenotypes in Smith-Magenis syndrome.
Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental syndromes characterized by repetitive behaviors and deficits in the core domains of language development and social interactions. Although the clinical criteria used to define ASDs are entirely behavioral, a wealth of research suggests that mechanisms underlying sensory processing and sensorimotor coupling are altered in individuals with ASDs, and that these differences significantly contribute to ASD pathology. However, the neural basis for these sensory and sensorimotor phenotypes are not completely understood.
Research into the developmental underpinnings of autism spectrum disorder (ASD) is hampered by a lack of techniques for describing neural development at the cellular and circuit levels. Ethan Scott and his colleagues plan to use zebrafish as a platform for anatomical and functional analyses of ASD etiology at the level of individual neurons and the circuits that they form. Zebrafish larvae are transparent, allowing neural development in the intact animal to be examined with a range of microscopic and optogenetic techniques.
Using SHANK3 conditional knock-in mice, Guoping Feng shows that adult re-expression of SHANK3 improves cellular and behavioral abnormalities, including ASD-like deficits.
Smith-Magenis syndrome (SMS) is an autism-like neurodevelopmental disorder that causes, among other things, motor and learning disability and obesity. SMS affects 1 in 15,000 to 25,000 people, mostly due to the spontaneous loss of a segment of chromosome 17 in the sperm or the egg that produces the embryo. Loss of one copy of the RAI1 gene, which is located within this chromosomal region, recapitulates most of the symptoms of SMS. Further, having an extra copy of the RAI1-containing segment causes the autism spectrum disorder Potocki-Lupski syndrome (PTLS). While alterations in RAI1 copy number has been linked to a number of neurodevelopmental disorders, the precise function of RAI1 in the brain remains unclear. Liqun Luo and his colleagues at Stanford University aim to understand why changing RAI1 copy number leads to compromised cognitive ability and autism-like symptoms.