Institute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, 518132, China.
Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Nat Commun. 2023 Jan 31;14(1):503. 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.
记忆可以通过新的经验以特定或泛化的方式进行修改。突触连接的变化对于记忆存储至关重要，但尚不清楚与不同记忆相关的突触变化如何在神经元回路中分布，以及这种分布如何影响新经验的特定或泛化修改。在这里，我们表明，使用两种不同的听觉刺激（CS）和足部电击（US）进行恐惧条件反射会导致小鼠运动皮层第 5 层锥体神经元的不同树突分支上的树突棘消除。随后的恐惧消退会导致 CS 特异性的棘形成和冻结行为的消退。相比之下，由 >2 种不同 CS-US 引起的恐惧条件反射引起的棘消除通常共存于同一树突分支上。恐惧消退会诱导 CS 非特异性的棘形成和广泛的恐惧消退。此外，激活表达生长抑素的中间神经元会增加同一树突分支上由不同 CS-US 引起的棘消除的发生，并促进恐惧消退的泛化。这些发现表明，新经验对现有记忆的特定或泛化修改取决于先前经验引起的突触变化是在个体树突分支水平上分离还是共存。
