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 language | English (US) |
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Pages (from-to) | 659-675.e6 |
Journal | Neuron |
Volume | 108 |
Issue number | 4 |
DOIs | |
State | Published - Nov 25 2020 |
Keywords
- Fmr1
- Fragile X
- autism
- circuit
- hypothalamus
- nucleus accumbens
- oxytocin
- reward
- single-cell RNA sequencing
- social
ASJC Scopus subject areas
- General Neuroscience