Xiangdong Wang1  · Jiaguo Wu1  · Mengna Liu1  · Kun Zhang6,7 · Xinping Yuan1  · Fangting Xing1  · Wenjie Xu2  · Yulin Zheng1  · Yifei Wu1  · Lin Luo1  · Xinyi Ding1  · Ge Gao1  · Mengping Wei1  · Jing Liang6,7 · Chen Zhang1,2,3,4,5

1 School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China 

2 School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China 

3 College of Basic Medicine, Inner Mongolia Medical University, Hohhot 010110, China 

4 State Key Laboratory of Translational Medicine and Innovative Drug Development, Nanjing 210000, China 

5 Chinese Institute for Brain Research, Beijing 102206, China 

6 State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China 

7 Department of Psychology, University of Chinese Academy of Sciences, Beijing 100101, China

Abstract

Protein Tyrosine Phosphatase Receptor Type O (PTPRO) is a synaptic cell adhesion molecule that is essential for synapse formation in vitro; however, its in vivo role remains unclear. Using PTPRO-knockout mice, we found that PTPRO deletion reduced the number of synapses and impaired both excitatory and inhibitory synaptic transmission. PTPRO knockout also disrupted hippocampal long-term potentiation and caused learning and memory deficits in the water maze as well as in fear conditioning. Notably, overexpression of the N-terminal extracellular domain of PTPRO rescued the frequencies of miniature excitatory postsynaptic currents and inhibitory postsynaptic currents, indicating that this domain is required to regulate synapse number and transmission. Collectively, these data demonstrate that PTPRO is essential for maintaining synapse number, synaptic transmission, long-term potentiation, and learning and memory functions in vivo.

Keywords

Synaptic transmission; Long-term potentiation; Synapse formation; Learning and memory; PTPRO

[SpringerLink]