2024-03-29T13:48:05Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1246942021-12-27T16:31:43Zcom_10261_105com_10261_1col_10261_358
00925njm 22002777a 4500
dc
Figueiro-Silva, Joana
author
Gruart, Agnès
author
Clayton, Kevin B.
author
Podlesniy, Petar
author
Abad, Alba
author
Gasull, Xavier
author
Delgado-García, José María
author
Trullas, Ramón
author
2015-04-08
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. © 2015 the authors
Journal of Neuroscience 35(14): 5504-5521 (2015)
http://hdl.handle.net/10261/124694
10.1523/JNEUROSCI.2548-14.2015
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100003329
25855168
excitatory synapses
Kv7.2 potassium channels
long-term potentiation
Neuronal pentraxin 1 negatively regulates excitatory synapse density and synaptic plasticity