Network-Level Analysis of Social Brain Activation in Mice with Autistic Phenotypes
Kemecsei Róbert Gergely
János Szentágothai Neurosciences
Dr. Bereczki Dániel
HUN-REN KOKI előadóterem
2025-10-31 11:00:00
Neuromorphology and cell biology
Dr. Alpár Alán
Dr. Zachar Gergely
Dr. Négyessy László
Dr. Horváth András
Dr. Réthelyi János
Dr. Puska Gina
Dr. Farkas Imre
Dr. Hanics János
Autism Spectrum Disorder (ASD) is characterized by deficits in social communication, repetitive behaviors, and sensory sensitivities, linked to disruptions in synaptogenesis, neuronal migration, and neurotransmitter imbalances. Increasingly, ASD is recognized as a disorder of neural connectivity, with altered synchrony across networks governing social and emotional regulation. The Social Decision-Making Network (SDMN), a conserved system regulating social behaviors, provides critical insights into ASD’s neural underpinnings.
This study examines the effects of embryonic valproic acid (VPA) exposure—an established rodent model of ASD—on social behavior and brain network connectivity. Male VPA treated and control (CTR) animals underwent social separation and reinstatement paradigms, revealing reduced social preference and impaired recognition of conspecifics in VPA-treated animals. Connectivity analysis indicated significant disruptions in SDMN function, with CTR animals displaying strong internal connectivity between key regions, including the lateral septum (LS), bed nucleus of the stria terminalis (BNST), and ventral pallidum (VP). In VPA-treated animals, SDMN connectivity was diminished, while connections with stress-regulating areas, such as the interpeduncular nucleus (IPN) and lateral hypothalamic area (LHA), were strengthened, reflecting maladaptive stress engagement. c-Fos immunohistochemistry revealed hyperactivation of the nucleus accumbens (NAcc) during social reinstatement in VPA-treated animals. ELISA assays demonstrated significantly reduced dopamine (DA) levels in the NAcc, suggesting a disconnect between heightened neural activity and deficient dopaminergic signaling. Gene mapping highlighted dysregulated pathways involved in neuronal migration and tract formation during the critical period of VPA exposure, reinforcing the developmental basis of these connectivity disruptions.
These findings underscore ASD as a disorder of large-scale network dysfunction, characterized by SDMN deficits, heightened stress pathway engagement, and dopaminergic alterations. This network-level perspective offers new insights into ASD pathophysiology and potential therapeutic strategies.
