Interaction between Long-Term Potentiation and Depression in CA1 Synapses: Temporal Constrains, Functional Compartmentalization and Protein Synthesis

Information arriving at a neuron via anatomically defined pathways undergoes spatial and temporal encoding. A proposed mechanism by which temporally and spatially segregated information is encoded at the cellular level is based on the interactive properties of synapses located within and across functional dendritic compartments. We examined cooperative and interfering interactions between long-term synaptic potentiation (LTP) and depression (LTD), two forms of synaptic plasticity thought to be key in the encoding of information in the brain. Two approaches were used in CA1 pyramidal neurons of the mouse hippocampus: (1) induction of LTP and LTD in two separate synaptic pathways within the same apical dendritic compartment and across the basal and apical dendritic compartments; (2) induction of LTP and LTD separated by various time intervals (0–90 min). Expression of LTP/LTD interactions was spatially and temporally regulated. While they were largely restricted within the same dendritic compartment (compartmentalized), the nature of the interaction (cooperation or interference) depended on the time interval between inductions. New protein synthesis was found to regulate the expression of the LTP/LTD interference. We speculate that mechanisms for compartmentalization and protein synthesis confer the spatial and temporal modulation by which neurons encode multiplex information in plastic synapses.经解剖学定义的通路抵达神经元的信息，需经历空间与时间编码过程。学界已提出的、在细胞水平实现时空分离信息编码的机制，基于位于功能树突亚区内部及跨功能树突亚区的突触交互特性。我们研究了长时程突触增强（long-term synaptic potentiation, LTP）与长时程突触抑制（long-term synaptic depression, LTD）之间的协同与干扰交互作用；这两类突触可塑性被认为是大脑信息编码的核心机制。本研究在小鼠海马CA1区锥体神经元中采用了两种实验方案：（1）在同一顶树突亚区内的两条独立突触通路，以及跨基树突与顶树突亚区的通路中，分别诱导LTP与LTD；（2）以不同时间间隔（0~90分钟）先后诱导LTP与LTD。LTP与LTD的交互作用表达受到时空双重调控。尽管这类交互作用大多局限于同一树突亚区内（即区室化特性），但其交互本质（协同或干扰）取决于两次诱导之间的时间间隔。研究发现，新生蛋白质合成可调控LTP与LTD的干扰性交互作用表达。我们推测，树突亚区区室化与蛋白质合成相关机制，可赋予神经元在可塑性突触中编码多通道信息的时空调控能力。