Pubmed du 26/10/25
1. Potasiewicz A, Popik P, Nikiforuk A. Analysis of rat vocalizations as a tool for assessing the effects of α7nAChR PAMs in a neurodevelopmental model of autism. Behav Brain Res. 2025: 115876.
Autism spectrum disorder (ASD) is commonly associated with impairments in communication, and ultrasonic vocalizations (USVs) in rodents serve as a translational tool to probe such deficits. We examined the effects of positive allosteric modulators (PAMs) of the α7 nicotinic acetylcholine receptor (α7nAChR), compounds CCMI and PNU120596, on vocal communication in a rat model of ASD induced by prenatal valproic acid (VPA) exposure. Leveraging a multimodal analytic framework, we investigated not only conventional acoustic variables but also temporal structure, syntactic organization, and cluster-based vocal repertoires. Analyses revealed that male but not female offspring exposed to VPA emitted fewer USVs and showed reduced vocal activity, reflected in fewer bouts and fewer calls per bout. Temporal analysis revealed persistent reductions across testing sessions in males, whereas females exhibited reductions in the late phase of calling. PAM treatments did not restore USV quantity or vocal activity in VPA-exposed males but partially normalized inter-call intervals, indicating selective effects on temporal dynamics. Acoustic features such as duration, bandwidth, and peak frequency remained largely unaltered by VPA or PAMs, except for a modest bandwidth reduction in VPA-exposed females. Cluster-based and syntax analyses confirmed sex-specific vocal profiles and revealed that PAMs modulated vocal syntax in both control and VPA-exposed animals, with compound- and context-dependent effects. These included increased usage of canonical trill calls and reductions in low-frequency or complex transitions, partially restoring disrupted communication patterns. The present study highlights a multimodal approach to USV profiling in animal models of socio-communicative deficits and suggests that α7nAChR PAMs exert subtle yet beneficial effects on the vocal timing and syntactic structure of communication, with implications for addressing syntactic disruptions in ASD-related vocal behaviors.
