Vaidya Sachin P, Li Guanchun, Chitwood Raymond A, Li Yiding, Magee Jeffrey C
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, USA.
Nat Neurosci. 2025 Jun 4. doi: 10.1038/s41593-025-01986-3.
How brain networks connected by labile synapses store new information without catastrophically overwriting previous memories remains poorly understood. To examine this, we tracked the same population of hippocampal CA1 place cells (PCs) as mice learned a task for 7 days. We found evidence of memory formation as both the number of PCs maintaining a stable place field and the stability of individual PCs progressively increased across the week until most of the representation was composed of long-term stable PCs. The stable PCs disproportionately represented task-related learned information, were retrieved earlier within a behavioral session and showed a strong correlation with behavioral performance. Both the initial formation of PCs and their retrieval on subsequent days were accompanied by prominent signs of behavioral timescale synaptic plasticity (BTSP), suggesting that even stable PCs were re-formed by synaptic plasticity each session. Further experimental evidence supported by a cascade-type state model indicates that CA1 PCs increase their stability each day they are active, eventually forming a highly stable population. The results suggest that CA1 memory is implemented by an increase in the likelihood of new neuron-specific synaptic plasticity, as opposed to extensive long-term synaptic weight stabilization.
由不稳定突触连接的脑网络如何在不灾难性地覆盖先前记忆的情况下存储新信息，目前仍知之甚少。为了研究这一问题，我们在小鼠学习一项任务的7天时间里，追踪了海马CA1区相同群体的位置细胞（PCs）。我们发现了记忆形成的证据，因为在这一周内，维持稳定位置野的PCs数量以及单个PCs的稳定性都在逐渐增加，直到大部分表征由长期稳定的PCs组成。稳定的PCs不成比例地代表了与任务相关的学习信息，在行为过程中更早被检索到，并且与行为表现呈现出强烈的相关性。PCs的初始形成及其在随后几天的检索都伴随着行为时间尺度突触可塑性（BTSP）的显著迹象，这表明即使是稳定的PCs在每次行为过程中也会通过突触可塑性重新形成。由级联型状态模型支持的进一步实验证据表明，CA1区的PCs在活跃的每一天都会增加其稳定性，最终形成一个高度稳定的群体。结果表明，CA1区的记忆是通过新的神经元特异性突触可塑性可能性的增加来实现的，而不是通过广泛的长期突触权重稳定化。
