Parallel Social Information Processing Circuits Are Differentially Impacted in Autism

Eastman M. Lewis, Genevieve L. Stein-O'Brien, Alejandra V. Patino, Romain Nardou, Cooper D. Grossman, Matthew Brown, Bidii Bangamwabo, Ndeye Ndiaye, Daniel Giovinazzo, Ian Dardani, Connie Jiang, Loyal A. Goff, Gül Dölen

Research output: Contribution to journalArticlepeer-review

Abstract

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. Here we provide the first comprehensive characterization of magnocellular and parvocellular oxytocin neurons in male mice, validated across anatomical, projection target, electrophysiological, and transcriptional criteria. We next use 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 enriched in parvocellular compared with magnocellular 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.

Original languageEnglish (US)
Pages (from-to)659-675.e6
JournalNeuron
Volume108
Issue number4
DOIs
StatePublished - Nov 25 2020

Keywords

  • Fmr1
  • Fragile X
  • autism
  • circuit
  • hypothalamus
  • nucleus accumbens
  • oxytocin
  • reward
  • single-cell RNA sequencing
  • social

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'Parallel Social Information Processing Circuits Are Differentially Impacted in Autism'. Together they form a unique fingerprint.

Cite this