Impermanence of dendritic spines in live adult CA1 hippocampus

By A. Attardo, James E. Fitzgerald, Mark J. Schnitzer. Nature, 2015

349 citations recorded by the source corpus.

The mammalian hippocampus is crucial for episodic memory formation and transiently retains information for about 3–4 weeks in adult mice and longer in humans. Although neuroscientists widely believe that neural synapses are elemental sites of information storage, there has been no direct evidence that hippocampal synapses persist for time intervals commensurate with the duration of hippocampal-dependent memory. Here we tested the prediction that the lifetimes of hippocampal synapses match the longevity of hippocampal memory. By using time-lapse two-photon microendoscopy in the CA1 hippocampal area of live mice, we monitored the turnover dynamics of the pyramidal neurons’ basal dendritic spines, postsynaptic structures whose turnover dynamics are thought to reflect those of excitatory synaptic connections. Strikingly, CA1 spine turnover dynamics differed sharply from those seen previously in the neocortex. Mathematical modelling revealed that the data best matched kinetic models with a single population of spines with a mean lifetime of approximately 1–2 weeks. This implies ∼100% turnover in ∼2–3 times this interval, a near full erasure of the synaptic connectivity pattern. Although N-methyl-d-aspartate (NMDA) receptor blockade stabilizes spines in the neocortex, in CA1 it transiently increased the rate of spine loss and thus lowered spine density. These results reveal that adult neocortical and hippocampal pyramidal neurons have divergent patterns of spine regulation and quantitatively support the idea that the transience of hippocampal-dependent memory directly reflects the turnover dynamics of hippocampal synapses.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/bbd03344ee790403f1f50f27cfbbcef65f165621

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Citations in the corpus

The content of hippocampal “replay” (2018, background): “Given recent findings that hippocampal map may not be as stable as once thought (Attardo et al., 2015; Rubin et al., 2015; Ziv et al., 2013), the ability to flexibly add neurons to an existing framework may facilitate, rather than hinder, rapid acquisition of information (Tse et al., 2007), or it…”
Dynamic Reorganization of Neuronal Activity Patterns in Parietal Cortex. (2017, neutral): “In some cases, only a small fraction of synaptic connections persist over weeks (Attardo et al., 2015; Stettler et al., 2006; Trachtenberg et al., 2002).”
Deep Rewiring: Training very sparse deep networks (2017, background): “Synaptic connectivity in the brain is highly dynamic in the sense that new synapses are constantly rewired, especially during learning (Holtmaat et al., 2005; Stettler et al., 2006; Attardo et al., 2015; Chambers & Rumpel, 2017).”
The Biology of Forgetting – A Perspective (2017, background): “An early declarative memory might be encoded by a group of hippocampal neurons but the engram becomes distributed to engram cells in other brain regions through the process of systems consolidation (Kandel et al., 2014; Dudai et al., 2015; Rubin et al., 2015; Attardo et al., 2015).”
The Persistence and Transience of Memory. (2017, background): “Even in basal states, it is likely that there is considerable synaptic turnover in the hippocampus, with turnover rates in the hippocampus likely higher than those in other brain regions (Attardo et al., 2015).”
Causes and consequences of representational drift (2019, background): “For example, in the hippocampus, all dendritic spines are expected to turn over in the period of several weeks [7].”