Although autism is a neurodevelopmental disorder, few animal studies of autism have adopted a neurodevelopmental perspective. Sensorimotor disturbances are among the earliest signs of atypical development in autism, and rapid eye movement (REM) sleep is known to be disrupted in children with autism. Interestingly, one of the defining features of REM sleep is myoclonic twitching, which is thought to play a critical role in promoting sensorimotor development and functional connectivity. Myoclonic twitches are jerky movements of the limbs, head, face and eyes that occur abundantly and exclusively during REM sleep. Critically, sensory feedback from twitching limbs is a primary driver of neural activity and functional connectivity throughout the sensorimotor system, suggesting that myoclonic twitches play a role in shaping, tuning and mapping the developing brain.
To investigate possible links between alterations in REM sleep and sensorimotor disturbances in autism, Mark Blumberg’s laboratory is investigating the neonatal expression of myoclonic twitching in a mouse model of 16p11.2 deletion. Preliminary findings from Blumberg’s SFARI Explorer Award indicate that 16p11.2 deletion mice show pronounced deficits in both the quantity and patterning of limb twitching during the neonatal period. Building on these findings, Blumberg’s group plans to assess the neural causes and consequences of decreased twitching in 16p11.2 deletion mice. With respect to causes, the team will record from the red nucleus — a midbrain structure that produces forelimb and hindlimb twitching — with an expectation that the 16p11.2 deletion mice will show reduced neural activity in this structure during REM sleep at ages when these mice also exhibit decreased rates of twitching. With respect to consequences, Blumberg’s group will assess the effects of decreased sensory feedback from twitching on both brain activity and functional connectivity within and between key sensorimotor structures. Altogether, the proposed experiments uniquely combine behavioral and neurophysiological measures to provide novel insights into the contributions of sleep to the early development of the sensorimotor system and how that process can go awry in autism and related neurodevelopmental disorders.