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      Phase-Locked Inhibition, but Not Excitation, Underlies Hippocampal Ripple Oscillations in Awake Mice In Vivo

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          Sharp wave-ripple (SWR) oscillations play a key role in memory consolidation during non-rapid eye movement sleep, immobility, and consummatory behavior. However, whether temporally modulated synaptic excitation or inhibition underlies the ripples is controversial. To address this question, we performed simultaneous recordings of excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) and local field potentials (LFPs) in the CA1 region of awake mice in vivo. During SWRs, inhibition dominated over excitation, with a peak conductance ratio of 4.1 ± 0.5. Furthermore, the amplitude of SWR-associated IPSCs was positively correlated with SWR magnitude, whereas that of EPSCs was not. Finally, phase analysis indicated that IPSCs were phase-locked to individual ripple cycles, whereas EPSCs were uniformly distributed in phase space. Optogenetic inhibition indicated that PV + interneurons provided a major contribution to SWR-associated IPSCs. Thus, phasic inhibition, but not excitation, shapes SWR oscillations in the hippocampal CA1 region in vivo.


          • High-resolution synaptic current recording during sharp wave-ripples (SWRs) in vivo

          • Inhibition dominates over excitation during SWRs in the hippocampal CA1 region

          • Phasic inhibition, but not excitation, is phase-locked to individual ripple cycles

          • PV + interneurons substantially contribute to SWR-associated inhibitory conductance


          Using high-resolution whole-cell recording of postsynaptic current from CA1 pyramidal neurons in awake mice, Gan et al. find that during sharp wave-ripples, inhibition dominates over excitation, is phase-locked to individual ripple cycles, and is primarily mediated by PV + interneurons.

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          Most cited references 14

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          Awake hippocampal sharp-wave ripples support spatial memory.

          The hippocampus is critical for spatial learning and memory. Hippocampal neurons in awake animals exhibit place field activity that encodes current location, as well as sharp-wave ripple (SWR) activity during which representations based on past experiences are often replayed. The relationship between these patterns of activity and the memory functions of the hippocampus is poorly understood. We interrupted awake SWRs in animals learning a spatial alternation task. We observed a specific learning and performance deficit that persisted throughout training. This deficit was associated with awake SWR activity, as SWR interruption left place field activity and post-experience SWR reactivation intact. These results provide a link between awake SWRs and hippocampal memory processes, which suggests that awake replay of memory-related information during SWRs supports learning and memory-guided decision-making.
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            Replay of neuronal firing sequences in rat hippocampus during sleep following spatial experience.

            The correlated activity of rat hippocampal pyramidal cells during sleep reflects the activity of those cells during earlier spatial exploration. Now the patterns of activity during sleep have also been found to reflect the order in which the cells fired during spatial exploration. This relation was reliably stronger for sleep after the behavioral session than before it; thus, the activity during sleep reflects changes produced by experience. This memory for temporal order of neuronal firing could be produced by an interaction between the temporal integration properties of long-term potentiation and the phase shifting of spike activity with respect to the hippocampal theta rhythm.
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              In vivo, low-resistance, whole-cell recordings from neurons in the anaesthetized and awake mammalian brain.

              A blind patch-clamp technique for in vivo whole-cell recordings in the intact brain is described. Recordings were obtained from various neuronal cell types located 100-5,000 microm from the cortical surface. Access resistance of recordings was as low as 10 M Omega but increased with recording depth and animal age. Recordings were remarkably stable and it was therefore possible to obtain whole-cell recordings in awake, head-fixed animals. The whole-cell configuration permitted rapid dialysis of cells with a calcium buffer. In most neurons very little ongoing action potential (AP) activity was observed and the spontaneous firing rates were up to 50-fold less than what has been reported by extracellular unit recordings. AP firing in the brain might therefore be far sparser than previously thought.

                Author and article information

                Cell Press
                18 January 2017
                18 January 2017
                : 93
                : 2
                : 308-314
                [1 ]IST Austria (Institute of Science and Technology Austria), Am Campus 1, A-3400 Klosterneuburg, Austria
                Author notes
                []Corresponding author peter.jonas@

                Present address: Department of Speech Language Pathology and Audiology, National Taipei University of Nursing and Health Science, Taipei 11219, Taiwan


                Present address: Center for Drug Evaluation, Taipei 11557, Taiwan


                Present address: University of Vienna, Dr. Bohr-Gasse 7, Vienna Biocenter, A-1030 Vienna, Austria


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                © 2017 The Author(s)

                This is an open access article under the CC BY license (



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