title: Impermanence of dendritic spines in live adult CA1 hippocampus.
abstract: 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.
authors.affiliation: 1] James H. Clark Center for Biomedical Engineering &Sciences, Stanford University, Stanford, California 94305, USA [2] Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
authors.forename: Alessio
authors.initials: A
authors.lastname: Attardo
authors.affiliation: James H. Clark Center for Biomedical Engineering &Sciences, Stanford University, Stanford, California 94305, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Fitzgerald
authors.affiliation: 1] James H. Clark Center for Biomedical Engineering &Sciences, Stanford University, Stanford, California 94305, USA [2] Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA [3] CNC Program, Stanford University, Stanford, California 94305, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Schnitzer
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology* / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism*; D004724:Endoscopy; D007700:Kinetics; D008297:Male; D061212:Memory, Episodic; D051379:Mice; D019579:Neocortex / Q000166:cytology / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D017785:Photons; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate