Generalized extinction of fear memory depends on co-allocation of synaptic plasticity in dendrites

• Published in: Nature communications Vol. 14; no. 1; p. 503
• Main Authors: Xu, Zhiwei, Geron, Erez, Pérez-Cuesta, Luis M., Bai, Yang, Gan, Wen-Biao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.01.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 631/378/1595; 631/378/87; Animals; Auditory pathways; Auditory stimuli; Conditioned stimulus; Conditioning; Cortex (motor); Dendrites; Dendritic spines; Dendritic structure; Extinction behavior; Extinction, Psychological; Fear; Fear conditioning; Freezing; Generalization, Psychological; Humanities and Social Sciences; Interneurons; Memory; Mice; multidisciplinary; Neuronal Plasticity; Neurons; Pyramidal cells; Science; Science (multidisciplinary); Somatostatin; Spine; Synapses; Synaptic plasticity; Tonic immobility
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-35805-9

Memories can be modified by new experience in a specific or generalized manner. Changes in synaptic connections are crucial for memory storage, but it remains unknown how synaptic changes associated with different memories are distributed within neuronal circuits and how such distributions affect specific or generalized modification by novel experience. Here we show that fear conditioning with two different auditory stimuli (CS) and footshocks (US) induces dendritic spine elimination mainly on different dendritic branches of layer 5 pyramidal neurons in the mouse motor cortex. Subsequent fear extinction causes CS-specific spine formation and extinction of freezing behavior. In contrast, spine elimination induced by fear conditioning with >2 different CS-USs often co-exists on the same dendritic branches. Fear extinction induces CS-nonspecific spine formation and generalized fear extinction. Moreover, activation of somatostatin-expressing interneurons increases the occurrence of spine elimination induced by different CS-USs on the same dendritic branches and facilitates the generalization of fear extinction. These findings suggest that specific or generalized modification of existing memories by new experience depends on whether synaptic changes induced by previous experiences are segregated or co-exist at the level of individual dendritic branches. How memories are modified by new experiences remain elusive. Here, authors show that specific or generalized modification of memories depends on whether synaptic changes associated with previous memories are segregated or co-exist in dendritic branches.