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Hippocampal CA1 Ripples as Inhibitory Transients.

Malerba P, Krishnan GP, Fellous JM, Bazhenov M - PLoS Comput. Biol. (2016)

Bottom Line: Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep.We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration.Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, California, United States of America.

ABSTRACT
Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep. Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation. In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3. In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations. Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition. We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration. Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network.

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Predictions from ripple network model.(a) Stereotypical ripple LFP has a duration independent from CA3 input length. On the left, the duration of CA3 input is reported. In each group, shown in gray are the actual band-passed LFPs for 40 ripples, while the black line is their average. The black dot marks where each average ripple ends. Next to the LFPs, a schematic of the full network used in this figure (as in Fig 2) (b). The percentage of pyramidal cells spiking on every ripple increases with the magnitude of CA3 input to pyramidal cells population. (c) Effect of inhibition on pyramidal cell recruitment to ripples. Histograms of the percent of pyramidal cells spiking in any given ripple in three conditions: default (black bars), inhibition on interneurons increased to 5ms (red bars), inhibition on pyramidal cells increased to 6ms (green bars). Bars heights have been normalized by total number of ripples. Note that increasing inhibition on interneurons un-inhibits pyramidal cell spiking, while increased inhibition on pyramidal cells predictably suppresses pyramidal cell firing during ripples. (d) Increasing inhibition time scale has almost no effect on ripple frequency. Histograms of ripple frequency under the same three conditions as in panel c.
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pcbi.1004880.g004: Predictions from ripple network model.(a) Stereotypical ripple LFP has a duration independent from CA3 input length. On the left, the duration of CA3 input is reported. In each group, shown in gray are the actual band-passed LFPs for 40 ripples, while the black line is their average. The black dot marks where each average ripple ends. Next to the LFPs, a schematic of the full network used in this figure (as in Fig 2) (b). The percentage of pyramidal cells spiking on every ripple increases with the magnitude of CA3 input to pyramidal cells population. (c) Effect of inhibition on pyramidal cell recruitment to ripples. Histograms of the percent of pyramidal cells spiking in any given ripple in three conditions: default (black bars), inhibition on interneurons increased to 5ms (red bars), inhibition on pyramidal cells increased to 6ms (green bars). Bars heights have been normalized by total number of ripples. Note that increasing inhibition on interneurons un-inhibits pyramidal cell spiking, while increased inhibition on pyramidal cells predictably suppresses pyramidal cell firing during ripples. (d) Increasing inhibition time scale has almost no effect on ripple frequency. Histograms of ripple frequency under the same three conditions as in panel c.

Mentions: Since the input current (representing the sum of synchronized spiking in CA3) caused ripples to initiate, we asked if ripples would continue oscillating for as long as the input was present. Fig 4A shows that the ripple LFP duration stayed un-varied independently of the different CA3 input durations we tested. The band-passed LFPs for 40 ripples across different input durations are shown in gray, while the black line is their average. The graph shows that even if spiking was still enhanced for the duration of CA3 inputs, the organized oscillatory activity was lost after about 60 ms for all cases considered. This emphasizes that CA1 can control ripple duration, even if it cannot control their initiation.


Hippocampal CA1 Ripples as Inhibitory Transients.

Malerba P, Krishnan GP, Fellous JM, Bazhenov M - PLoS Comput. Biol. (2016)

Predictions from ripple network model.(a) Stereotypical ripple LFP has a duration independent from CA3 input length. On the left, the duration of CA3 input is reported. In each group, shown in gray are the actual band-passed LFPs for 40 ripples, while the black line is their average. The black dot marks where each average ripple ends. Next to the LFPs, a schematic of the full network used in this figure (as in Fig 2) (b). The percentage of pyramidal cells spiking on every ripple increases with the magnitude of CA3 input to pyramidal cells population. (c) Effect of inhibition on pyramidal cell recruitment to ripples. Histograms of the percent of pyramidal cells spiking in any given ripple in three conditions: default (black bars), inhibition on interneurons increased to 5ms (red bars), inhibition on pyramidal cells increased to 6ms (green bars). Bars heights have been normalized by total number of ripples. Note that increasing inhibition on interneurons un-inhibits pyramidal cell spiking, while increased inhibition on pyramidal cells predictably suppresses pyramidal cell firing during ripples. (d) Increasing inhibition time scale has almost no effect on ripple frequency. Histograms of ripple frequency under the same three conditions as in panel c.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4836732&req=5

pcbi.1004880.g004: Predictions from ripple network model.(a) Stereotypical ripple LFP has a duration independent from CA3 input length. On the left, the duration of CA3 input is reported. In each group, shown in gray are the actual band-passed LFPs for 40 ripples, while the black line is their average. The black dot marks where each average ripple ends. Next to the LFPs, a schematic of the full network used in this figure (as in Fig 2) (b). The percentage of pyramidal cells spiking on every ripple increases with the magnitude of CA3 input to pyramidal cells population. (c) Effect of inhibition on pyramidal cell recruitment to ripples. Histograms of the percent of pyramidal cells spiking in any given ripple in three conditions: default (black bars), inhibition on interneurons increased to 5ms (red bars), inhibition on pyramidal cells increased to 6ms (green bars). Bars heights have been normalized by total number of ripples. Note that increasing inhibition on interneurons un-inhibits pyramidal cell spiking, while increased inhibition on pyramidal cells predictably suppresses pyramidal cell firing during ripples. (d) Increasing inhibition time scale has almost no effect on ripple frequency. Histograms of ripple frequency under the same three conditions as in panel c.
Mentions: Since the input current (representing the sum of synchronized spiking in CA3) caused ripples to initiate, we asked if ripples would continue oscillating for as long as the input was present. Fig 4A shows that the ripple LFP duration stayed un-varied independently of the different CA3 input durations we tested. The band-passed LFPs for 40 ripples across different input durations are shown in gray, while the black line is their average. The graph shows that even if spiking was still enhanced for the duration of CA3 inputs, the organized oscillatory activity was lost after about 60 ms for all cases considered. This emphasizes that CA1 can control ripple duration, even if it cannot control their initiation.

Bottom Line: Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep.We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration.Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, California, United States of America.

ABSTRACT
Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep. Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation. In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3. In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations. Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition. We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration. Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network.

Show MeSH
Related in: MedlinePlus