Department of Neuroscience, Columbia University, New York, NY 10032, United States; Division of Systems Neuroscience, New York State Psychiatric Institute, New York, NY 10032, United States.
Neurobiol Learn Mem. 2019 Oct;164:107049. doi: 10.1016/j.nlm.2019.107049. Epub 2019 Jul 27.
Learning and memory have long been thought to involve changes in synaptic connections between neurons. However, in many cases learning-related plasticity also involves changes in the excitability of neurons. These findings have raised questions about the relative importance of these two types of mechanisms to behavioral learning, and also about the extent to which they involve shared or unique molecular mechanisms. We have taken a reductionist approach to these questions by addressing them in a simple model organism, Aplysia californica. Studies of a semi-intact Aplysia siphon withdrawal preparation suggest that classical conditioning involves an increase in the evoked firing of sensory neurons (SNs) as well as facilitation of the monosynaptic PSP to motor neurons (MNs). Furthermore, these two mechanisms may act cooperatively at the cellular level: increased SN firing produces more PSPs, each of which is facilitated, leading to a multiplicative increase in depolarization of the MN and siphon withdrawal. The changes in SN firing and the monosynaptic PSP also share several mechanisms at the molecular level, suggesting that they may both be due in part to a decrease in K current that causes an increase in SN excitability as well as an increase in SN spike width and thus increased transmitter release. However, changes in the monosynaptic PSP also involve additional mechanisms that are not shared and may affect different aspects of synaptic transmission as well. Studies of operant conditioning of feeding suggest that it involves similar mechanisms as classical conditioning of siphon withdrawal. In particular, for both types of associative learning adenylyl cyclase appears to serve as a molecular coincidence detector that leads to increased activation of PKA and changes in excitability of key neurons in the neural circuit. Furthermore, in both cases those changes in excitability make an important contribution to the behavioral learning.
学习和记忆长期以来被认为涉及神经元之间突触连接的变化。然而，在许多情况下，与学习相关的可塑性也涉及神经元兴奋性的变化。这些发现引发了关于这两种机制对行为学习的相对重要性的问题，以及它们在多大程度上涉及共享或独特的分子机制。我们通过在简单的模式生物——加利福尼亚海兔中解决这些问题，采用了一种简化论的方法。对一种半完整的加利福尼亚海兔虹吸管撤退准备的研究表明，经典条件作用涉及感觉神经元（SNs）诱发放电的增加以及对运动神经元（MNs）的单突触 PSP 的易化。此外，这两种机制可能在细胞水平上协同作用：增加 SN 放电会产生更多的 PSP，每个 PSP 都会被易化，导致 MN 和虹吸管撤退的去极化呈乘法增加。SN 放电和单突触 PSP 的变化在分子水平上也有几个共同的机制，这表明它们可能部分是由于 K 电流的减少，导致 SN 兴奋性增加以及 SN 尖峰宽度增加，从而增加递质释放。然而，单突触 PSP 的变化还涉及其他不共享的机制，这些机制可能会影响突触传递的不同方面。进食操作性条件作用的研究表明，它涉及与虹吸管撤退的经典条件作用类似的机制。特别是对于这两种类型的联想学习，腺苷酸环化酶似乎作为一个分子巧合探测器，导致 PKA 的激活增加和神经回路中关键神经元兴奋性的变化。此外，在这两种情况下，兴奋性的变化对行为学习都有重要贡献。
