Opposite effects of fear conditioning and extinction on dendritic spine remodelling

摘要

学习和记忆被认为涉及神经连接的物理和功能rn改变，但相对来说人们对与行为相关的回路所rn发生的结构变化却知之甚少。两项新的研究凸rn显了可能决定学习和神经弹性的其中一些物理rn改变及机制所起的作用。Warl等人分析了参与rn恐惧回路的神经元，发现“恐惧学习”诱导了rn树突棘的丢失，恐惧的消失引起树突中稳定树rn突棘曾经所在的同一区域中树突棘的再生长。rnFu等人发现，在“运动学习”过程中特定回路rn的重复激发会诱导新的树突棘簇的形成，而这rn些新的树突棘簇仅仅在延长的学习过程中才始rn终存在。%It is generally believed that fear extinction is a form of new learning that inhibits rather than erases previously acquired fear memories1"3. Although this view has gained much support from behavioural and electrophysiological studies1"10, the hypothesis that extinction causes the partial erasure of fear memories remains viable. Using trans-cranial two-photon microscopy11'12, we investigated how neural circuits are modified by fear learning and extinction by examining the formation and elimination of postsynaptic dendritic spines of layer-V pyramidal neurons in the mouse frontal association cortex. Here we show that fear conditioning by pairing an auditory cue with a footshock increases the rate of spine elimination. By contrast, fear extinction by repeated presentation of the same auditory cue without a footshock increases the rate of spine formation. The degrees of spine remodelling induced by fear conditioning and extinction strongly correlate with the expression and extinction of conditioned fear responses, respectively. Notably, spine elimination and formation induced by fear conditioning and extinction occur on the same dendritic branches in a cue- and location-specific manner: cue-specific extinction causes formation of dendritic spines within a distance of two micrometres from spines that were eliminated after fear conditioning. Furthermore, reconditioning preferentially induces elimination of dendritic spines that were formed after extinction. Thus, within vastly complex neuronal networks, fear conditioning, extinction and reconditioning lead to opposing changes at the level of individual synapses. These findings also suggest that fear memory traces are partially erased after extinction.