MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, University Walk, Bristol, UK.
Semin Cell Dev Biol. 2011 Jul;22(5):506-13. doi: 10.1016/j.semcdb.2011.07.017. Epub 2011 Jul 22.
Studies performed on low-density primary neuronal cultures have enabled dissection of molecular and cellular changes during N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP). Various electrophysiological and chemical induction protocols were developed for the persistent enhancement of excitatory synaptic transmission in hippocampal neuronal cultures. The characterisation of these plasticity models confirmed that they share many key properties with the LTP of CA1 neurons, extensively studied in hippocampal slices using electrophysiological techniques. For example, LTP in dissociated hippocampal neuronal cultures is also dependent on Ca(2+) influx through post-synaptic NMDA receptors, subsequent activation and autophosphorylation of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and an increase in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor insertion at the post-synaptic membrane. The availability of models of LTP in cultured hippocampal neurons significantly facilitated the monitoring of changes in endogenous postsynaptic receptor proteins and the investigation of the associated signalling mechanisms that underlie LTP. A central feature of LTP of excitatory synapses is the recruitment of AMPA receptors at the postsynaptic site. Results from the use of cell culture-based models started to establish the mechanism by which synaptic input controls a neuron's ability to modify its synapses in LTP. This review focuses on key features of various LTP induction protocols in dissociated hippocampal neuronal cultures and the applications of these plasticity models for the investigation of activity-induced changes in native AMPA receptors.
在低密度原代神经元培养物上进行的研究使我们能够剖析 N-甲基-D-天冬氨酸(NMDA)受体依赖性长时程增强(LTP)过程中的分子和细胞变化。已经开发出各种电生理和化学诱导方案来持续增强海马神经元培养物中兴奋性突触传递。这些可塑性模型的特征证实,它们与在海马切片中使用电生理技术广泛研究的 CA1 神经元的 LTP 具有许多关键特性。例如,分离的海马神经元培养物中的 LTP 也依赖于通过突触后 NMDA 受体的 Ca2+内流,随后 Ca2+/钙调蛋白依赖性蛋白激酶 II(CaMKII)的激活和自动磷酸化以及α-氨基酸-3-羟基-5-甲基异恶唑-4-丙酸(AMPA)受体在突触后膜上的插入增加。在培养的海马神经元中 LTP 模型的可用性极大地促进了对内源性突触后受体蛋白变化的监测以及对基础 LTP 的相关信号机制的研究。兴奋性突触 LTP 的一个核心特征是在突触后位点募集 AMPA 受体。基于细胞培养模型的结果开始确定突触输入控制神经元在 LTP 中改变其突触的能力的机制。本综述重点介绍了分离的海马神经元培养物中各种 LTP 诱导方案的关键特征,以及这些可塑性模型在研究活性诱导的天然 AMPA 受体变化中的应用。