Hicks A, Davis S, Rodger J, Helme-Guizon A, Laroche S, Mallet J
Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR C9923, Hôpital de la Pitié Salpêtrière, Paris, France.
Neuroscience. 1997 Jul;79(2):329-40. doi: 10.1016/s0306-4522(96)00700-2.
The messenger RNAs encoding proteins of the exocytotic machinery were measured at different times following the induction of long-term potentiation or increasing neuronal activity in the dentate gyrus of the rat in vivo. In situ hybridization revealed that from the many messenger RNAs that encode proteins involved in regulated exocytosis, only those encoding synapsin I and syntaxin 1B were specifically increased. The levels of messenger RNA encoding both synapsin I and syntaxin 1B were increased on the ipsilateral side of the dorsal dentate gyrus 2 and 5 h following the induction of long-term potentiation. Syntaxin 1B was also increased in the ventral dentate gyrus at the same time-points. On the contralateral side of the dentate gyrus there was an increase in both synapsin I and syntaxin 1B at 5 h only. All of these long-term potentiation-induced changes were prevented when the tetanus was delivered in the presence of the N-methyl-D-aspartate receptor antagonist. (D(-)-2-amino-5-phosphonopentanoic acid. Immunocytochemical staining revealed that protein levels for both synapsin I and syntaxin 1B were elevated in the mossy fibre terminal zone of CA3 5 h after the induction of long-term potentiation. In addition to these plasticity-induced changes, a transient increase in the messenger RNA encoding syntaxin 1B was observed at 2 h in conditions of high intensity stimulation of the perforant path to increase the level of cellular activation, but this change was not maintained even when high intensity stimulation was sustained for 5 h. No changes in either of the messenger RNAs were observed under low frequency stimulation and pseudotetanus at either time-points. These results show that an overall increase in neuronal excitation within a neuronal network can be differentiated from a change in synaptic strength at a specific subset of the synapses, where only synaptic plasticity leads to long-term changes in the expression of selective members of the exocytotic machinery. Altered concentrations of key vesicle proteins may thus provide the means for modulation of neurotransmitter release over long time-periods. The persistent long-term potentiation-induced postsynaptic increase in messenger RNAs encoding these presynaptic proteins has important implications for the propagation of signals downstream from the site of long-term potentiation induction in hippocampal neural networks, and highlights a candidate molecular mechanism for mediating the propagation of synaptic plasticity in such networks.
在大鼠体内海马齿状回诱导长时程增强（LTP）或增加神经元活性后的不同时间，对编码胞吐机制蛋白的信使核糖核酸（mRNA）进行了测定。原位杂交显示，在众多编码参与调节性胞吐作用相关蛋白的mRNA中，只有编码突触素I和 syntaxin 1B的mRNA特异性增加。在诱导LTP后2小时和5小时，背侧齿状回同侧编码突触素I和syntaxin 1B的mRNA水平升高。在相同时间点，腹侧齿状回的syntaxin 1B也增加。仅在5小时时，齿状回对侧的突触素I和syntaxin 1B均增加。当在N - 甲基 - D - 天冬氨酸受体拮抗剂（D(-)-2 - 氨基 - 5 - 磷酸戊酸）存在的情况下给予强直刺激时，所有这些LTP诱导的变化均被阻止。免疫细胞化学染色显示，在诱导LTP后5小时，CA3区苔藓纤维终末区的突触素I和syntaxin 1B蛋白水平升高。除了这些可塑性诱导的变化外，在高强度刺激穿通通路以增加细胞激活水平的条件下，在2小时时观察到编码syntaxin 1B的mRNA短暂增加，但即使高强度刺激持续5小时，这种变化也未持续。在低频刺激和假强直刺激的任何时间点，两种mRNA均未观察到变化。这些结果表明，神经元网络内神经元兴奋的总体增加可与特定突触子集处突触强度的变化区分开来，其中只有突触可塑性会导致胞吐机制的选择性成员表达的长期变化。关键囊泡蛋白浓度的改变可能因此提供了在长时间内调节神经递质释放的手段。LTP诱导的编码这些突触前蛋白的mRNA在突触后持续增加，这对海马神经网络中LTP诱导位点下游信号的传播具有重要意义，并突出了介导此类网络中突触可塑性传播的候选分子机制。
