Hippocampal mossy cells exhibit some of the earliest signs of increased excitability in the Tg2576 model of Alzheimer’s disease neuropathology

• DOI: 10.1002/alz.069163
• Publication Date: 2022-12-20T15:19:16Z
• Authors: David Alcantara‐G...; Chiara Criscuolo; Justin J Botterill; Christos Lisgaras; Meghan Kennedy; Helen E Scharfman
• Keywords: Neuropathology

Abstract Background Alzheimer’s disease (AD) is a neurodegenerative illness characterized by progressive accumulation of amyloid beta (Aβ) and neurofibrillary tangles, with cognitive impairment altered neural activity. Hyperexcitability in the early stages AD contribute to Aβ impairment, aggravating progression AD. However, hyperexcitability origin not clear. This study aimed test whether mossy cells (MCs), an excitatory cell hippocampal dentate gyrus, show increased excitability at network generation. Indeed, alterations MCs epilepsy. role has been substantially explored. Methods Intrinsic synaptic properties granule (GCs) from WT Tg2576 mice ages (1‐2 m.o.) were whole‐cell patch‐clamp recordings. Synaptic included frequency amplitude spontaneous postsynaptic potentials (EPSPs) inhibitory currents (EPSCs IPSCs). Deterioration morphology was evaluated using Nissl staining GluR2/3 labeling light‐ confocal microscopy. deposition McSA1 antibody. Results GCs did have any significant difference their intrinsic properties, as we shown previously ∼3 m.o. enhanced input GCs, depicted augmented IPSC (7.16 vs 14.04 events/s) NMDA‐mediated EPSC frequencies (0.81 1.41 found. Interestingly, had EPSP (5.75 9.44 events/s), showed depolarized RMP (‐72.88 ‐58.36 mV), reduced rheobase (145.56 47.14 pA), AP (98.14 76.66 time‐to‐peak (552.75 266.16 ms) maximum rise (171.44 88.68 mV/ms) decay slopes (‐61.17 ‐42.38 mV/ms). The correlation between #APs current injected fired significantly more APs (SE ZD = 0.34; z 2.48). robust intracellular aggregation without morphological change. Conclusions changes suggest that could be cause occurring later GCs. In this manner, important contributor