UCLA

Structural plasticity mediated by addition and elimination of dendritic spines is thought to underlie the formation of long-term memory. However, the spatial relationship of those structural activities during learning and memory remains unclear. Using in vivo two-photon microscopy, I track spine dynamics in mouse retrosplenial cortex (RSC) during contextual and spatial learning. I report that learning leads to addition of new spines that are spatially clustered, and the amount of clustering is predicted by spine turnover prior to learning. Both spine measures are correlated with learning and memory performance. Accordingly, a genetic manipulation by heterozygous mutation of Ccr5 that enhances pre-learning spine turnover also enhances learning-related spine clustering, as well as future learning and memory performance. New spines related to one memory do not form cluster with spines related to a distinct memory. In contrast, spines gained from one repetitive task tend to cluster with each other. Remarkably, clustered new spines are usually added on dendritic segments with rapid spine turnover, revealing the presence of hotspots on dendritic tree where elevated rates of spine turnover facilitate clustered spine addition associated with memory. One implication of these findings is that increased spine turnover may allow neurons to more efficiently sample the synaptic space during learning in order to optimize information acquisition. Once acquired, spine clustering may stabilize this information, thus strengthening memory circuits.