|
Hippocampal Ripples Down-Regulate Synapses
Science 30 Mar 2018: Vol. 359, Issue 6383, pp. 1524-1527 Hippocampal ripples down-regulate synapses Hiroaki Norimoto, et.al. Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan. Laboratory for Systems Neurophysiology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako City, Saitama, Japan. Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo, Japan. Center for Information and Neural Networks, National Institute of Information and Communications Technology, Osaka, Japan. [paraphrase] The specific effects of sleep on synaptic plasticity remain unclear. We report that mouse hippocampal sharp-wave ripple oscillations serve as intrinsic events that trigger long-lasting synaptic depression. Silencing of sharp-wave ripples during slow-wave states prevented the spontaneous down-regulation of net synaptic weights and impaired the learning of new memories. The synaptic down-regulation was dependent on the N-methyl-d-aspartate receptor and selective for a specific input pathway. Thus, our findings are consistent with the role of slow-wave states in refining memory engrams by reducing recent memory-irrelevant neuronal activity and suggest a previously unrecognized function for sharp-wave ripples. Hippocampal and neocortical plasticity during the awake state is dominated by net synaptic potentiation, whereas plasticity during sleep, especially during slow-wave (SW) sleep, is dominated by net synaptic depression. These circadian alternations in synaptic weights manifest a homeostatic balancing function for sleep; however, the mechanisms behind the synaptic downscaling during SW states remain to be identified. During SW states—which include SW sleep, awake immobility, and consummatory behavior—the hippocampus spontaneously emits transient high-frequency field oscillations called sharp-wave ripples (SWRs). SWRs represent the reactivation of neurons involved in recently acquired memory and contribute to memory consolidation. Although memory consolidation may rely on synaptic plasticity, no consensus has yet been reached on the relationship between SWRs and synaptic plasticity. We discovered that hippocampal SWRs triggered persistent synaptic depression and that silencing SWRs impaired subsequent new learning, which appears to be consistent with the hypothesis that overstrengthened synapses impair neuronal responsiveness and saturate the ability to learn. We consider three possible but not mutually exclusive mechanisms by which SWRs induce synaptic depression: (i) synaptic delay lines in activity propagation during SWRs decouple hippocampal network activity and weaken synaptic weights, (ii) uncorrelated presynaptic and postsynaptic activity during SWRs causes heterosynaptic depression because memory-irrelevant cells are rarely fired during SWRs, and (iii) the event frequency of SWRs reaches ~1 Hz after spatial exploration, which may induce homosynaptic depression. Notably, field stimulation with the event timing of SWRs after spatial exploration was sufficient to induce depression, suggesting the importance of the role of the timing, rather than the spike contents, of SWRs. On the other hand, mushroom spines did not shrink in SWR-emitting slices; that is, not all spines were equally subject to depression. This finding is in agreement with the hypothesis that sleep leads to net depression through the removal of unstable synapses. A recent in vitro study demonstrated that the relative spike timings of CA3 and CA1 place cells during SWRs cause synaptic potentiation. Thus, synapses involved in memory engrams may escape depression through presynaptic and postsynaptic coactivation. Together with our findings, we propose dual roles of SWR-induced depression: (i) SWRs reset unnecessary synapses and avoid memory saturation, and (ii) SWRs purify recent memory engrams by shearing irrelevant neuronal activity and perhaps strengthening memory-relevant synapses, thereby contributing to memory consolidation. [end of paraphrase]
Return to — Memory Formation and Retention Link to — Memory Consolidatation Return to — Hippocampus |