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Activity‐dependent regulation of release probability at excitatory hippocampal synapses: a crucial role of fragile X mental retardation protein in neurotransmission
Author(s) -
Wang XiaoSheng,
Peng ChunZi,
Cai WeiJun,
Xia Jian,
Jin Daozhong,
Dai Yuqiao,
Luo XueGang,
Klyachko Vitaly A.,
Deng PanYue
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12546
Subject(s) - excitatory postsynaptic potential , neurotransmission , neuroscience , fragile x syndrome , postsynaptic potential , synaptic plasticity , synaptic fatigue , hippocampal formation , biology , metaplasticity , postsynaptic density , inhibitory postsynaptic potential , receptor , genetics
Transcriptional silencing of the F mr1 gene encoding fragile X mental retardation protein ( FMRP ) causes fragile X syndrome ( FXS ), the most common form of inherited intellectual disability and the leading genetic cause of autism. FMRP has been suggested to play important roles in regulating neurotransmission and short‐term synaptic plasticity at excitatory hippocampal and cortical synapses. However, the origins and mechanisms of these FMRP actions remain incompletely understood, and the role of FMRP in regulating synaptic release probability and presynaptic function remains debated. Here we used variance‐mean analysis and peak‐scaled nonstationary variance analysis to examine changes in both presynaptic and postsynaptic parameters during repetitive activity at excitatory CA 3– CA 1 hippocampal synapses in a mouse model of FXS . Our analyses revealed that loss of FMRP did not affect the basal release probability or basal synaptic transmission, but caused an abnormally elevated release probability specifically during repetitive activity. These abnormalities were not accompanied by changes in excitatory postsynaptic current kinetics, quantal size or postsynaptic α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor conductance. Our results thus indicate that FMRP regulates neurotransmission at excitatory hippocampal synapses specifically during repetitive activity via modulation of release probability in a presynaptic manner. Our study suggests that FMRP function in regulating neurotransmitter release is an activity‐dependent phenomenon that may contribute to the pathophysiology of FXS .