A novel mechanism of memory loss in Alzheimer's disease mice via the degeneration of entorhinal-CA1 synapses

作者：Yang, X.; Yao, C.; Tian, T.; Li, X.; Yan, H.; Wu, J.; Li, H.; Pei, L.; Liu, D.; Tian, Q.; Zhu, L-Q^*; Lu, Y.^*

来源：Molecular Psychiatry, 2018, 23(2): 199-210.

DOI：10.1038/mp.2016.151

• DEEP BRAIN-STIMULATION
• SPATIAL REPRESENTATION SYSTEM
• MILD COGNITIVE IMPAIRMENT
• AMYLOID PRECURSOR PROTEIN
• TRANSGENIC MOUSE MODEL
• SYNAPTIC PLASTICITY
• TG2576 MICE
• PLACE CELLS
• GRID CELLS
• OCEAN CELLS

The entorhinal cortex (EC) is one of the most vulnerable brain regions that is attacked during the early stage of Alzheimer's disease (AD). Here, we report that the synaptic terminals of pyramidal neurons in the EC layer II (ECIIPN) directly innervate CA1 parvalbumin (PV) neurons (CA1(PV)) and are selectively degenerated in AD mice, which exhibit amyloid-beta plaques similar to those observed in AD patients. A loss of ECIIPN-CA1(PV) synapses disables the excitatory and inhibitory balance in the CA1 circuit and impairs spatial learning and memory. Optogenetic activation of ECIIPN using a theta burst paradigm rescues ECIIPN-CA1(PV) synaptic defects and intercepts the decline in spatial learning and memory. These data reveal a novel mechanism of memory loss in AD mice via the selective degeneration of the ECIIPN-CA1(PV) pathway.

• 出版日期2018-2
• 单位华中科技大学