Publicação
Brain rhythms and cell assembly dynamics in the prefrontal cortex of a GPRASP2 mouse model of autism spectrum disorder
| Resumo: | Introduction: Autism spectrum disorder is a neurodevelopmental disorder characterized by social deficits and repetitive or stereotyped behaviors. Previous studies have shown neuroanatomical alterations in the prefrontal cortex in autistic patients. Despite its causal role in social behavior, the dynamics of prefrontal circuits during social experiences remain poorly understood, hindering the identification of putative activity biomarkers of social deficits. Aim: To compare the behavioral and neurophysiological signatures between wild type and a conditional GPRASP2 mouse model of autism spectrum disorder, when engaged in social experiences.Methods: We implemented a headgear for dual-site, in vivo electrophysiological recordings in freely behaving mice, and recorded the neuronal activity in prefrontal circuits of control and knockout mice engaged in social experiences. Animals were compared in terms of behavioral metrics (sociability and preference for social novelty) and in terms of prefrontal spectral signatures in the delta, theta, and beta bands.Results: Regarding behavioral metrics, wild type mice displayed significant sociability, without preference for novel or familiar conspecifics. While knockout mice also lacked preference for social novelty of familiarity, the analysis of their sociability was ultimately inconclusive. During social experiences, wild type mice showed increased theta power (8-12 Hz) in prefrontal cortex compared to epochs of exploration in an empty maze. This spectral property was absent in knockout mice.Discussion: In our behavioral approach, GPRASP2 mice did not conclusively meet criteria for social dysfunction, due to low sample size and putative methodological differences in relation to the social tests employed in previous publications. In contrast, wild type and GPRASP2 mice differed in their spectral signatures, although the stability and specificity of these correlates requires further validation. Conclusion: Wild type and knockout mice show different prefrontal spectral signatures during social experiences. These might be used as putative markers of social dysfunction, and their dissection at a fundamental level might allow the identification of the circuit mechanisms responsible for social impairment in autism spectrum disorder. |
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| Autores principais: | Fernandes, Emanuel Ferreira |
| Assunto: | Brain rhythms autism spectrum disorder prefrontal cortex in vivo electrophysiology GPRASP2 mouse model Ritmos do cérebro perturbação do espectro do autismo córtex pré-frontal eletrofisiologia in vivo modelo de murganho GPRASP2 |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Coimbra |
| Idioma: | inglês |
| Origem: | Estudo Geral - Universidade de Coimbra |
| Resumo: | Introduction: Autism spectrum disorder is a neurodevelopmental disorder characterized by social deficits and repetitive or stereotyped behaviors. Previous studies have shown neuroanatomical alterations in the prefrontal cortex in autistic patients. Despite its causal role in social behavior, the dynamics of prefrontal circuits during social experiences remain poorly understood, hindering the identification of putative activity biomarkers of social deficits. Aim: To compare the behavioral and neurophysiological signatures between wild type and a conditional GPRASP2 mouse model of autism spectrum disorder, when engaged in social experiences.Methods: We implemented a headgear for dual-site, in vivo electrophysiological recordings in freely behaving mice, and recorded the neuronal activity in prefrontal circuits of control and knockout mice engaged in social experiences. Animals were compared in terms of behavioral metrics (sociability and preference for social novelty) and in terms of prefrontal spectral signatures in the delta, theta, and beta bands.Results: Regarding behavioral metrics, wild type mice displayed significant sociability, without preference for novel or familiar conspecifics. While knockout mice also lacked preference for social novelty of familiarity, the analysis of their sociability was ultimately inconclusive. During social experiences, wild type mice showed increased theta power (8-12 Hz) in prefrontal cortex compared to epochs of exploration in an empty maze. This spectral property was absent in knockout mice.Discussion: In our behavioral approach, GPRASP2 mice did not conclusively meet criteria for social dysfunction, due to low sample size and putative methodological differences in relation to the social tests employed in previous publications. In contrast, wild type and GPRASP2 mice differed in their spectral signatures, although the stability and specificity of these correlates requires further validation. Conclusion: Wild type and knockout mice show different prefrontal spectral signatures during social experiences. These might be used as putative markers of social dysfunction, and their dissection at a fundamental level might allow the identification of the circuit mechanisms responsible for social impairment in autism spectrum disorder. |
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