Inhibitory Neural Network’s Impairments at Hippocampal CA1 LTP in an Aged Transgenic Mouse Model of Alzheimer’s Disease

• Main Authors: Hyeon Jeong Seo, Jung Eun Park, Seong-Min Choi, Taekyoung Kim, Soo Hyun Cho, Kyung-Hwa Lee, Woo Keun Song, Juhyun Song, Han-Seong Jeong, Dong Hyun Kim, Byeong C. Kim
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: International Journal of Molecular Sciences
• Subjects: Alzheimer’s disease; hippocampus; CA1; hippocampal long-term potentiation; NRG1-ErbB4 signaling
• Online Access: https://www.mdpi.com/1422-0067/22/2/698

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a rapid accumulation of amyloid β (Aβ) protein in the hippocampus, which impairs synaptic structures and neuronal signal transmission, induces neuronal loss, and diminishes memory and cognitive functions. The present study investigated the impact of neuregulin 1 (NRG1)-ErbB4 signaling on the impairment of neural networks underlying hippocampal long-term potentiation (LTP) in 5xFAD mice, a model of AD with greater symptom severity than that of TG2576 mice. Specifically, we observed parvalbumin (PV)-containing hippocampal interneurons, the effect of NRG1 on hippocampal LTP, and the functioning of learning and memory. We found a significant decrease in the number of PV interneurons in 11-month-old 5xFAD mice. Moreover, synaptic transmission in the 5xFAD mice decreased at 6 months of age. The 11-month-old transgenic AD mice showed fewer inhibitory PV neurons and impaired NRG1-ErbB4 signaling than did wild-type mice, indicating that the former exhibit the impairment of neuronal networks underlying LTP in the hippocampal Schaffer-collateral pathway. In conclusion, this study confirmed the impaired LTP in 5xFAD mice and its association with aberrant NRG1-ErbB signaling in the neuronal network.