Parallel social information processing circuits are differentially impacted in autism

Parallel processing circuits are thought to dramatically expand the network capabilities of the nervous system. Magnocellular and parvocellular oxytocin neurons have been proposed to subserve two parallel streams of social information processing, which allow a single molecule to encode a diverse array of ethologically distinct behaviors, although to date direct evidence to support this hypothesis is lacking. Here we provide the first comprehensive characterization of magnocellular and parvocellular oxytocin neurons, validated across anatomical, projection target, electrophysiological, and transcriptional criteria. We next used novel multiple feature selection tools in Fmr1 KO mice to provide direct evidence that normal functioning of the parvocellular but not magnocellular oxytocin pathway is required for autism-relevant social reward behavior. Finally, we demonstrate that autism risk genes are uniquely enriched in parvocellular oxytocin neurons. Taken together these results provide the first evidence that oxytocin pathway specific pathogenic mechanisms account for social impairments across a broad range of autism etiologies. Overall design: 146 SMART-Seq2 full-length cDNA scRNA-Seq libraries from enriched oxytocinergic neurons from P23 OT-2A-Flp::fdGFP+ mouse hypothalamus paraventricular nucleus. Cells were sequenced to an average depth of 1,424,499 ±77,731 paired-end 50bp reads per neuron on the Illumina HiSeq 2500 platform. 21 parvocellular OT neurons and 215 magnocelluar OT neurons are represented.