Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.09.23.753714

Xenon improves autism-like behaviors in mice through potentiation of PVT-CeA glutamatergic neurotransmission

Zhu, J.·Ruan, Y.·Weng, J.·Xu, X.·Wu, Z.·Yu, Y.·Li, H.·Li, X.·Tong, J.·Ou, Y.·Shu, Q.·Ma, D.
View original source ↗Export metadata ↓

Abstract

Autism spectrum disorder (ASD) is a common neurodevelopmental disease with no currently effective treatments. In this study, Xenon (Xe), a noble gas used clinically as an anesthetic and a neuroprotectant, has been investigated for its potential therapeutic effects in ASD. Two genetic ASD mouse models (Mef2c mutant and Shank3-/- mice) were exposed to a low concentration of xenon (25%) mixed with oxygen (30%) and balanced with nitrogen for a single exposure of 30 min or for 10 min per day for 10 days. These Xe exposure paradigms rescued ASD-like behaviors in both male and female mice. The behavioral improvements persisted for up to 10 days following termination of the 10-day exposure paradigm. Mechanistically, Xe reduced glutamic acid decarboxylase expression in the inhibitory neurons (verified with RNAseq) of the paraventricular thalamic nucleus (PVT) and decreased GABA release during social interaction. Targeted infusion of the GABAA receptor agonist muscimol into the PVT abolished the Xe-mediated behavioral improvements. Reduced GABAergic transmission following Xe exposure increased PVT glutamatergic neuronal activity. Chemogenetic inhibition of these neurons eliminated the therapeutic effects of Xe, whereas chemogenetic activation mimicked the Xe-induced behavioral improvements. Furthermore, opto-inhibition of PVT glutamatergic projections to the central amygdala (CeA) blocked Xe-mediated behavioral improvement. Opto-activation of the PVT-CeA glutamatergic circuit reversed ASD-like behaviors. These findings demonstrate that Xe ameliorates ASD-like phenotypes in mouse models by modulating the PVT Glu-CeA circuit, supporting Xe as a novel potential therapy for ASD.

Explore related subjects

animal behavior and cognitionPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Zhu, J., Ruan, Y., Weng, J., Xu, X., Wu, Z., Yu, Y., Li, H., Li, X., Tong, J., Ou, Y., Shu, Q., Ma, D.. 2026-09-25. Xenon improves autism-like behaviors in mice through potentiation of PVT-CeA glutamatergic neurotransmission. https://doi.org/10.64898/2026.09.23.753714

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Deconstructing Boldness: Latent behavioural structure across novelty, predation, and exploration in an endangered species translocation program

Risk-related behaviours including neophobia, exploration, and predator avoidance are often assumed to covary along a general boldness axis. Although some translocation studies have linked one or more of these behaviours with fitness, it is possible that the underlying behavioural structure varies under different selective environments. Conservation breeding programs provide a unique opportunity to evaluate the structure of behavioural correlations in a non-domestic species under artificial conditions. We tested whether risk-related behaviours represent a unified boldness syndrome in a captive population of the endangered Attwaters prairie chicken (APC; Tympanuchus cupido attwateri). We quantified the repeatable behaviours of 257 juveniles and compared 11 models of behavioural covariation structure using multivariate mixed models and confirmatory factor analysis. There was no support for a single risk-taking axis; instead, we found three dimensions representing responses to novelty and environmental stimuli (Engagement), predator avoidance (Threat Response), and maze exploration (Maze Progression). Our results indicate that these risk-related behaviours are not organized along a single axis in captive APCs, challenging assumptions that risk-taking represents a universal behavioural syndrome. To anticipate post-release success accurately, conservation managers should understand the exact behavioural architecture of the captive population rather than assume that the classical bold-shy structure occurs in all contexts.

animal behavior and cognition↗
bioRxiv2026

Social costs of group life: Larger groups have less affiliative behavior and more social conflict

The costs and benefits of sociality depend in part upon the size of groups. Therefore, individual behavior should vary across groups of different sizes, reflecting group size-dependent costs and benefits. Here, we test this prediction using a long-term dataset on wild female baboons (Papio cynocephalus x P. anubis). We find that individuals who live in larger groups suffer social costs: compared to animals in smaller groups, they experience more agonistic interactions, fewer grooming interactions, and sparser social networks. These social costs arise, in part, from a pattern in which relationships within dyads become more agonistic as group size increases (i.e., a given dyad exhibits fewer grooming interactions relative to agonistic interactions when it is living in a larger group). While individuals in large groups generally maintain the same number of strong bonds as individuals in small groups, they tend to develop weak bonds with a greater number of social partners that results in, on average, weaker bonds overall. Our results demonstrate that, despite potential benefits to large groups in terms of predation risk and intergroup competition, the social lives of individuals in larger groups involve less affiliation and more conflict in this wild primate population.

animal behavior and cognition↗
bioRxiv2026

Shared brain transcriptome signatures of social evolution and plasticity in shell-dwelling cichlid fishes

Inter-individual variability in phenotypic traits is widespread in nature both across and within species, with similar patterns of variation often occurring between and within species. Given that these two types of variation are generated by evolutionary and plasticity processes respectively, it raises the question to what extent the causal mechanisms underlying such variability at these two different levels are shared or not. To address this question, we studied the variation in brain transcriptomes in Tanganyikan cichlids that exhibit both intra- and interspecific variation in social behavior. We compared two facultatively social cichlid species, each containing naturally occurring solitary and social-living individuals, with a closely related obligatory solitary resembling the ancestral state. Differential gene expression and Gene Set Enrichment Analyses were performed in the telencephalon and diencephalon transcriptomes to investigate the molecular basis of both behavioral plasticity and the evolution of sociality. Behavioral plasticity involved few differentially expressed genes but extensive changes in biological pathways, supporting a highly polygenic architecture of social behavior. Across both species, social-living individuals consistently upregulated pathways involved in translation, protein homeostasis, and energy metabolism, whereas solitary individuals showed enrichment of neuronal morphogenesis, cell adhesion, and structural plasticity. Remarkably, these same functional programs were associated with the independent evolution of sociality, revealing a strong overlap between evolutionary and plastic transcriptional responses. This convergence was largely restricted to the telencephalon, while the diencephalon showed limited and inconsistent functional signatures. Together, our results support the repeated recruitment of gene regulatory programs during the evolution of sociality and demonstrate that behavioral plasticity and evolutionary transitions share common neurogenomic responses, consistent with a conserved genetic toolkit for social behavior.

animal behavior and cognition↗