The study examines the properties of VIP/calretinin-coexpressing I-S3 cells in the 3xTg mouse model of Alzheimer's disease (AD) at early stages of pathology. The key findings are:
VIP-expressing interneurons in the CA1 hippocampal region accumulate intracellular amyloid-β (Aβ) in 3-month-old 3xTg mice, but their density remains unaffected.
I-S3 cells in 3xTg mice exhibit elongated action potentials and decreased firing rates, which is associated with reduced inhibition of CA1 interneurons.
The heightened activity of CA1 interneurons, particularly during spatial decision-making and object exploration tasks, is not due to increased excitatory drive but rather stems from the reduced inhibitory tone from I-S3 cells.
The altered recruitment of CA1 interneurons impacts the activation of CA1 principal cells, suggesting early disruptions in CA1 network functionality.
These findings indicate that the modified firing patterns of I-S3 cells might initiate early-stage dysfunction in hippocampal CA1 circuits, potentially influencing the progression of AD pathology.
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by Michaud,F., ... : www.biorxiv.org 01-13-2024
https://www.biorxiv.org/content/10.1101/2024.01.12.575331v1Mélyebb kérdések