1. Variability in sub-threshold signaling linked to Alzheimer's disease emerges with age and amyloid plaque deposition in mouse ventral CA1 pyramidal neurons
- Author
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Yuliya Voskobiynyk, Timothy F. Musial, Gary X. D'Souza, Daniel A. Nicholson, Viviana Jimenez, Natividad Ybarra, Annalise E. Rogalsky, Loreece G. Haddad, John F. Disterhoft, Elizabeth Molina-Campos, Matthew L. Russo, Dane M. Chetkovich, Gabriel Carballo, M. Matthew Oh, and Krystina M. Neuman
- Subjects
0301 basic medicine ,Aging ,Patch-Clamp Techniques ,Amyloid ,Transgene ,Hippocampus ,Mice, Transgenic ,Plaque, Amyloid ,Biology ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Channelopathy ,Alzheimer Disease ,Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ,HCN channel ,medicine ,Animals ,Patch clamp ,CA1 Region, Hippocampal ,Pyramidal Cells ,General Neuroscience ,Endoplasmic reticulum ,Organ Size ,medicine.disease ,Disease Models, Animal ,030104 developmental biology ,Disease Progression ,biology.protein ,Neurology (clinical) ,Geriatrics and Gerontology ,Neuroscience ,030217 neurology & neurosurgery ,Signal Transduction ,Developmental Biology - Abstract
The hippocampus is vulnerable to deterioration in Alzheimer's disease (AD). It is, however, a heterogeneous structure, which may contribute to the differential volumetric changes along its septotemporal axis during AD progression. Here, we investigated amyloid plaque deposition along the dorsoventral axis in two strains of transgenic AD (ADTg) mouse models. We also used patch-clamp physiology in these mice to probe for functional consequences of AD pathogenesis in ventral hippocampus, which we found bears significantly higher plaque burden in the aged ADTg group compared to corresponding dorsal regions. Despite dorsoventral differences in amyloid load, ventral CA1 pyramidal neurons of aged ADTg mice exhibited subthreshold physiological changes similar to those previously reported in dorsal neurons, indicative of an HCN channelopathy, but lacked exacerbated suprathreshold accommodation. Additionally, HCN channel function could be rescued by pharmacological manipulation of the endoplasmic reticulum. These observations suggest that an AD-linked HCN channelopathy emerges in both dorsal and ventral CA1 pyramidal neurons, but that the former encounter an additional integrative obstacle in the form of reduced intrinsic excitability.
- Published
- 2021
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