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Altered projection-specific synaptic remodeling and its modification by oxytocin in an idiopathic autism marmoset model
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Altered projection-specific synaptic remodeling and its modification by oxytocin in an idiopathic autism marmoset model
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Journal Article
Altered projection-specific synaptic remodeling and its modification by oxytocin in an idiopathic autism marmoset model
2024
Overview
Alterations 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.
Using in vivo two-photon microscopy, the structural dynamics of synapses in the prefrontal cortex of an autism model marmoset were studied. In the marmoset, clustered dendritic spine generation was heightened, which was attenuated by oxytocin.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ 14/35
/ 14/69
/ Animals
/ Autism
/ Autism Spectrum Disorder - metabolism
/ Autistic Disorder - metabolism
/ Autistic Disorder - pathology
/ Biomedical and Life Sciences
/ Dendritic Spines - drug effects
/ Dendritic Spines - metabolism
/ Dendritic Spines - pathology
/ Female
/ Hormones
/ Male
/ Oxytocin
/ Prefrontal Cortex - drug effects
/ Prefrontal Cortex - metabolism
/ Prefrontal Cortex - pathology
/ Presynaptic Terminals - metabolism
