Deficits in neuronal architecture but not over-inhibition are main determinants of reduced neuronal network activity in a mouse model of overexpression of Dyrk1A.

ABSTRACT: In this study, we investigated the impact of Dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A) overexpression, a gene associated with Down syndrome, on hippocampal neuronal deficits in mice. Our findings revealed that mice overexpressing Dyrk1A (TgDyrk1A; TG) exhibited impaired hippocampal recognition memory, disrupted excitation-inhibition balance, and deficits in long-term potentiation (LTP). Specifically, we observed layer-specific deficits in dendritic arborization of TG CA1 pyramidal neurons in the stratum radiatum. Through computational modeling, we determined that these alterations resulted in reduced storage capacity and compromised integration of inputs, with decreased high γ oscillations. Contrary to prevailing assumptions, our model suggests that deficits in

SUBMITTER: Manubens-Gil L 

PROVIDER: S-EPMC10793573 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature