A novel mechanism of memory loss in Alzheimer's disease mice via the degeneration of entorhinal-CA1 synapses.
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 (CA1PV) and are selectively degenerated in AD mice, which exhibit amyloid-β plaques similar to those observed in AD patients. A loss of ECIIPN-CA1PVsynapses disables the excitatory and inhibitory balance in the CA1 circuit and impairs spatial learning and memory. Optogenetic activation of ECIIPNusing a theta burst paradigm rescues ECIIPN-CA1PVsynaptic 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-CA1PVpathway.
Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
X
X
Yang
Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
C
C
Yao
Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
T
T
Tian
Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
X
X
Li
Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
H
H
Yan
Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
J
J
Wu
Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
H
H
Li
The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.|Department of Neurobiology, Tongji School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
L
L
Pei
The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.|Department of Genetics, Tongji School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
D
D
Liu
The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.|Department of Pathophysiology, Tongji School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
Q
Q
Tian
The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.|Department of Pathophysiology, Tongji School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
L-Q
LQ
Zhu
Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
Y
Y
Lu
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001921:Brain; D056547:CA1 Region, Hippocampal / Q000503:physiopathology; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000503:physiopathology*; D006801:Humans; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons; D010320:Parvalbumins; D058225:Plaque, Amyloid; D017729:Presynaptic Terminals; D017966:Pyramidal Cells / Q000378:metabolism*; D013569:Synapses / Q000473:pathology
D010320:Parvalbumins
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