Dyscoordination of thalamic reticular spindles is associated with social memory deficits in mice and humans with autism spectrum disorder

Social memory, the ability to recognize and remember conspecifics, is frequently impaired in psychiatric disorders such as autism, yet the underlying mechanisms remain unclear. We examined the role of sleep spindles across non-rapid eye movement sleep in social memory consolidation, focusing on the sensory thalamic reticular nucleus (sTRN). Here we show that impaired spindles were associated with defective social memory. Through pharmacological/optogenetic manipulations and optical Ca2+ recordings, we demonstrated that parvalbumin-positive neurons in the sTRN (sTRNPvalb) are essential for sleep spindle generation, mediated by the sTRNPvalb–ventroposteromedial (VPM) thalamic nucleus circuit. Increasing the activity of the sTRNPvalb–VPM pathway could rescue impaired spindles and social memory deficits in Neuroligin 2 mutant mice. Moreover, we developed machine learning-based models to predict autism in children based on spindle eigenvalues. These findings underscore the critical role of spindles in social memory, suggesting spindles may serve as candidate diagnostic markers. The relationship between sleep spindles and social memory is not fully understood. Here authors identify a thalamic sleep spindle circuit that supports social memory consolidation and is disrupted in autism. Restoring spindle activity rescued social deficits in mice, and spindle features predicted autism in children.