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 (sTRN^Pvalb) are essential for sleep spindle generation, mediated by the sTRN^Pvalb–ventroposteromedial (VPM) thalamic nucleus circuit. Increasing the activity of the sTRN^Pvalb–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.