Neuronal Pentraxin 1 Negatively Regulates Excitatory Synapse Density and Synaptic Plasticity

被引:37
作者
Figueiro-Silva, Joana [1 ,2 ]
Gruart, Agnes [3 ]
Bernard Clayton, Kevin [1 ,2 ]
Podlesniy, Petar [1 ,2 ]
Alba Abad, Maria [1 ,2 ]
Gasull, Xavier [4 ,5 ]
Mara Delgado-Garcia, Jose [3 ]
Trullas, Ramon [1 ,2 ,5 ]
机构
[1] CSIC, Inst Invest Biomed Barcelona, Neurobiol Unit, Barcelona 08036, Spain
[2] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
[3] Univ Pablo de Olavide, Div Neurociencias, Seville 41013, Spain
[4] Univ Barcelona, Sch Med, Lab Neurophysiol, E-08036 Barcelona, Spain
[5] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona 08036, Spain
关键词
excitatory synapses; Kv7.2 potassium channels; long-term potentiation; POTASSIUM CHANNEL SUBUNITS; LONG-TERM-MEMORY; AMPA RECEPTORS; KCNQ2; SUBUNITS; SYNTAXIN; 1A; K+ CHANNEL; HIPPOCAMPAL; MEMBRANE; BRAIN; NARP;
D O I
10.1523/JNEUROSCI.2548-14.2015
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In mature neurons, the number of synapses is determined by a neuronal activity-dependent dynamic equilibrium between positive and negative regulatory factors. We hypothesized that neuronal pentraxin (NP1), a proapoptotic protein induced by low neuronal activity, could be a negative regulator of synapse density because it is found in dystrophic neurites in Alzheimer's disease-affected brains. Here, we report that knockdown of NP1 increases the number of excitatory synapses and neuronal excitability in cultured rat cortical neurons and enhances excitatory drive and long-term potentiation in the hippocampus of behaving mice. Moreover, we found that NP1 regulates the surface expression of the Kv7.2 subunit of the Kv7 family of potassium channels that control neuronal excitability. Furthermore, pharmacological activation of Kv7 channels prevents, whereas inhibition mimics, the increase in synaptic proteins evoked by the knockdown of NP1. These results indicate that NP1 negatively regulates excitatory synapse number by modulating neuronal excitability and show that NP1 restricts excitatory synaptic plasticity.
引用
收藏
页码:5504 / 5521
页数:18
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