Altered projection-specific synaptic remodeling and its modification by oxytocin in an idiopathic autism marmoset model

Author:

Noguchi JunORCID,Watanabe SatoshiORCID,Oga Tomofumi,Isoda Risa,Nakagaki Keiko,Sakai Kazuhisa,Sumida Kayo,Hoshino Kohei,Saito Koichi,Miyawaki Izuru,Sugano ErikoORCID,Tomita HiroshiORCID,Mizukami Hiroaki,Watakabe Akiya,Yamamori Tetsuo,Ichinohe NoritakaORCID

Abstract

AbstractAlterations in the experience-dependent and autonomous elaboration of neural circuits are assumed to underlie autism spectrum disorder (ASD), though it is unclear what synaptic traits are responsible. Here, utilizing a valproic acid–induced ASD marmoset model, which shares common molecular features with idiopathic ASD, we investigate changes in the structural dynamics of tuft dendrites of upper-layer pyramidal neurons and adjacent axons in the dorsomedial prefrontal cortex through two-photon microscopy. In model marmosets, dendritic spine turnover is upregulated, and spines are generated in clusters and survived more often than in control marmosets. Presynaptic boutons in local axons, but not in commissural long-range axons, demonstrate hyperdynamic turnover in model marmosets, suggesting alterations in projection-specific plasticity. Intriguingly, nasal oxytocin administration attenuates clustered spine emergence in model marmosets. Enhanced clustered spine generation, possibly unique to certain presynaptic partners, may be associated with ASD and be a potential therapeutic target.

Funder

MEXT | Japan Society for the Promotion of Science

National Center of Neurology and Psychiatry

Publisher

Springer Science and Business Media LLC

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