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

X Yang; C Yao; T Tian; X Li; H Yan; J Wu; H Li; L Pei; D Liu; Q Tian; L-Q Zhu; Y Lu

doi:10.1038/mp.2016.151

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

Mol Psychiatry. 2018 Feb;23(2):199-210. doi: 10.1038/mp.2016.151. Epub 2016 Sep 27.

Authors

X Yang^{1

2}, C Yao^{1

2}, T Tian^{1

2}, X Li^{1

2}, H Yan^{1

2}, J Wu^{1

2}, H Li^{1

2}, L Pei^{2

3}, D Liu^{2

4}, Q Tian^{2

5}, L-Q Zhu^{2

5}, Y Lu^{1

2}

Affiliations

¹ Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Neurobiology, Tongji School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Genetics, Tongji School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
⁵ Department of Pathophysiology, Tongji School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.

Abstract

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 (ECII_PN) directly innervate CA1 parvalbumin (PV) neurons (CA1_PV) and are selectively degenerated in AD mice, which exhibit amyloid-β plaques similar to those observed in AD patients. A loss of ECII_PN-CA1_PV synapses disables the excitatory and inhibitory balance in the CA1 circuit and impairs spatial learning and memory. Optogenetic activation of ECII_PN using a theta burst paradigm rescues ECII_PN-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 ECII_PN-CA1_PV pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / metabolism
Animals
Brain
CA1 Region, Hippocampal / physiopathology
Disease Models, Animal
Entorhinal Cortex / physiopathology*
Humans
Memory / physiology
Memory Disorders / metabolism
Memory Disorders / physiopathology*
Mice
Mice, Transgenic
Neurons
Parvalbumins
Plaque, Amyloid
Presynaptic Terminals
Pyramidal Cells / metabolism*
Synapses / pathology

Substances

Parvalbumins