Impermanence of dendritic spines in live adult CA1 hippocampus

• Published in: Nature (London) 2015-07, Vol.523 (7562), p.592-596
• Main Authors: Attardo, Alessio, Fitzgerald, James E., Schnitzer, Mark J.
• Format: Article
• Language: English
• Subjects: 14/69; 631/378/116/2395; 631/378/1595/1554; 631/378/2597/2599; Analysis; Animals; Brain; CA1 Region, Hippocampal - cytology; CA1 Region, Hippocampal - metabolism; Dendritic cells; Dendritic Spines - metabolism; Endoscopy; Genetic aspects; Humanities and Social Sciences; Kinetics; letter; Male; Mammals; Memory, Episodic; Methyl aspartate; Mice; Microscopy; multidisciplinary; Neocortex - cytology; Neocortex - metabolism; Neuronal Plasticity - physiology; Neurons; Neurosciences; Photons; Physiological aspects; Pyramidal Cells - cytology; Pyramidal Cells - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Science; Spine; Studies; Synapses - metabolism; Time Factors; Variance analysis
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature14467

A new microendoscopic method reveals that hippocampal dendritic spines in the CA1 region undergo a complete turnover in less than six weeks in adult mice; this contrasts with the much greater stability of synapses in the neocortex and provides a physical basis for the fact that episodic memories are only retained by the mouse hippocampus for a few weeks. Dendritic spine turnover in the hippocampus Episodic memories are formed in the mammalian hippocampus but retained there only for a few weeks, compared to the months and years of memory storage provided in the neocortex. Mark Schnitzer and colleagues have used a new microendoscopic method to reveal that hippocampal dendritic spines in the CA1 region undergo complete turnover in less than six weeks in mice, in contrast to the much greater stability of synapses in the neocortex. This work illustrates a possible physical basis for the transience of hippocampal memory processes. The mammalian hippocampus is crucial for episodic memory formation 1 and transiently retains information for about 3–4 weeks in adult mice and longer in humans 2 . Although neuroscientists widely believe that neural synapses are elemental sites of information storage 3 , 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 4 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 5 , 6 . Strikingly, CA1 spine turnover dynamics differed sharply from those seen previously in the neocortex 7 , 8 , 9 . 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 10 , 11 , 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 th