Bailey C H, Giustetto M, Zhu H, Chen M, Kandel E R
Howard Hughes Medical Institute, and Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York, NY 10032, USA.
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11581-6. doi: 10.1073/pnas.97.21.11581.
Studies of sensitization and classical conditioning of the gill-withdrawal reflex in Aplysia have shown that the synaptic connections between identified glutamatergic sensory neurons and motor neurons can be enhanced in one of two ways: by a heterosynaptic (modulatory input-dependent) mechanism that gives rise with repetition to long-term facilitation and by a homosynaptic (activity-dependent) mechanism that gives rise with repetition to a facilitation that is partially blocked by 2-amino-5-phosphonovaleric acid and by injection of 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetate (BAPTA) into the postsynaptic cell and is similar to long-term potentiation in the hippocampus. We here have examined how these two forms of facilitation interact at the level of an individual synaptic connection by using a culture preparation consisting of a single bifurcated sensory neuron that forms independent synaptic contacts with each of two spatially separated motor neurons. We find that the homosynaptic facilitation produced by a train of action potentials is cell wide and is evident at all of the terminals of the sensory neuron. By contrast, the heterosynaptic facilitation mediated by the modulatory transmitter serotonin (5-HT) can operate at the level of a single synapse. Homosynaptic activation gives rise to only a transient facilitation lasting a few hours, even when repeated in a spaced manner. The heterosynaptic facilitation produced by a single pulse of 5-HT, applied to one terminal of the sensory neuron, also lasts only minutes. However, when one or more homosynaptic trains of spike activity are paired with even a single pulse of 5-HT applied to one of the two branches of the sensory neuron, the combined actions lead to a selective enhancement in synaptic strength only at the 5-HT-treated branch that now lasts more than a day, and thus amplifies, by more than 20-fold, the duration of the individually produced homo- and heterosynaptic facilitation. This form of synapse-specific facilitation has unusual long-term properties. It does not require protein synthesis, nor is it accompanied by synaptic growth.
对海兔鳃收缩反射的敏感化和经典条件作用的研究表明，已确定的谷氨酸能感觉神经元与运动神经元之间的突触连接可以通过两种方式之一得到增强：一种是异突触（依赖调制输入）机制，重复刺激会导致长期易化；另一种是同突触（依赖活动）机制，重复刺激会导致易化，这种易化会被2-氨基-5-磷酸戊酸部分阻断，并且通过向突触后细胞注射1,2-双（2-氨基苯氧基）乙烷-N,N,N',N'-四乙酸（BAPTA）可观察到，它类似于海马体中的长时程增强。我们在此通过使用一种培养制剂来研究这两种易化形式在单个突触连接水平上是如何相互作用的，该制剂由单个分叉的感觉神经元组成，该神经元与两个空间上分离的运动神经元分别形成独立的突触联系。我们发现，一串动作电位产生的同突触易化在整个细胞范围内起作用，并且在感觉神经元的所有终末都很明显。相比之下，由调制递质5-羟色胺（5-HT）介导的异突触易化可以在单个突触水平上起作用。即使以间隔方式重复，同突触激活也只会产生持续数小时的短暂易化。施加于感觉神经元一个终末的单个5-HT脉冲所产生的异突触易化也仅持续数分钟。然而，当一串或多串动作电位与施加于感觉神经元两个分支之一的单个5-HT脉冲配对时，联合作用仅在5-HT处理的分支处导致突触强度的选择性增强，这种增强现在持续超过一天，因此将单独产生的同突触和异突触易化的持续时间放大了20多倍。这种形式的突触特异性易化具有不同寻常的长期特性。它不需要蛋白质合成，也不伴有突触生长。
