Recently a joint research effort uncovered the role of endophilin A1, a membrane-binding protein encoded by the disease-correlated gene
sh3gl2, in acute structural plasticity of dendritic spines during the acute phase of long-term potentiation (LTP) (
Journal of Cell Biology ,
https://doi.org/10.1083/jcb.202007172).
Neurons communicate with each other via specialized cellular structures called synapses, formed by axon terminals and opposing dendritic spines, the micron-sized membranous protrusions emanating from dendrites of neighboring neurons. One of the most important features of neuronal cells is synaptic plasticity, the ability of synapses to change their transmission efficacy in response to neural activity evoked by an experience. Consequently, our subsequent emotion, thoughts and behaviors are modified.
Synaptic plasticity is considered to be the cellular basis of learning and memory. During LTP of hippocampal CA1pyramidal neurons in the brain, a classical form of synaptic plasticity, neuronal activity induces not only size expansion of dendritic spines (termed structural plasticity), but also an increase in the number of AMPA receptors at the postsynaptic sites located in the plasma membrane of spine heads (termed functional plasticity) . How neural activity triggers rapid spine enlargement upon LTP induction remains a mystery.
In collaboration with Prof. LI Dong (Institute of Biophysics, Chinese Academy of Sciences), Prof. SHI Yun (Model Animal Research Center, Nanjing University), Prof. LIANG Xin (Tsinghua-Peking Center for Life Sciences, Tsinghua University) and Prof. MA Cong (Huazhong University of Science and Technology), researchers led by Prof. Jia-Jia LIU (Institute of Genetics and Developmental Biology, Chinese Academy of Sciences) applied super-resolution microscopy to visualize the dynamic changes in the plasma membrane and F-actin content in dendritic spines of hippocampal neurons undergoing LTP. They found that spine membrane expansion is spatially and temporally coupled with actin polymerization in the acute phase of synaptic potentiation. They then found that this membrane-cytoskeleton coupling was dramatically hampered in endophilin A1 gene knockout neurons.
Ca2+/calmodulin-mediated signaling plays a central role in LTP induction and expression. Upon LTP induction, Ca2+/calmodulin in dendritic spines enhances binding of endophilin A1 to the plasma membrane, which recruits p140Cap and cortactin, two cytoskeleton regulatory factors, to enable branched actin polymerization that subsequently provides the driving force for plasma membrane expansion to initiate spine enlargement.
Further studies revealed that the molecular functions of endophilin A1 in acute structural plasticity are essential for LTP expression and maintenance of pyramidal neurons in the hippocampal CA1 region and hippocampal-dependent spatial learning and memory.
These findings uncover a cellular mechanism for the acute morphological change of dendritic spines in response to neuronal activity, and demonstrate that the acute structural plasticity plays a vital role in LTP and long-lasting memory.
This research was supported by Ministry of Science and Technology, the National Natural Science Foundation of China and the research program of Chinese Academy of Sciences.
Contact:
Dr. Jia-jia LIU
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences
