During NREM sleep, hippocampal sharp-wave ripple (SWR) events are thought to stabilize memory traces for long-term storage in downstream neocortical structures. Within the neocortex, a set of distributed networks organized around retrosplenial cortex (RS-network) interact preferentially with the hippocampus purportedly to consolidate those traces. Transient bouts of slow oscillations and sleep spindles in this RS-network are often observed around SWRs, suggesting that these two activities are related and that their interplay possibly contributes to memory consolidation. To investigate how SWRs interact with the RS-network and spindles, we combined cortical wide-field voltage imaging, Electrocorticography, and hippocampal LFP recordings in anesthetized and sleeping mice. Here, we show that, during SWR, “up-states” and spindles reliably co-occur in a cortical subnetwork centered around the retrosplenial cortex. Furthermore, retrosplenial transient activations and spindles predict slow gamma oscillations in CA1 during SWRs. Together, our results suggest that retrosplenial–hippocampal interaction may be a critical pathway of information exchange between the cortex and hippocampus.
Hippocampal sharp‐wave ripples (SWRs) support the reactivation of memory representations, relaying information to neocortex during “offline” and sleep‐dependent memory consolidation. While blockade of NMDA receptors (NMDAR) is known to affect both learning and subsequent consolidation, the specific contributions of NMDAR activation to SWR‐associated activity remain unclear. Here, we combine biophysical modeling with in vivo local field potential (LFP) and unit recording to quantify changes in SWR dynamics following inactivation of NMDAR. In a biophysical model of CA3‐CA1 SWR activity, we find that NMDAR removal leads to reduced SWR density, but spares SWR properties such as duration, cell recruitment and ripple frequency. These predictions are confirmed by experiments in which NMDAR‐mediated transmission in rats was inhibited using three different NMDAR antagonists, while recording dorsal CA1 LFP. In the model, loss of NMDAR‐mediated conductances also induced a reduction in the proportion of cell pairs that co‐activate significantly above chance across multiple events. Again, this prediction is corroborated by dorsal CA1 single‐unit recordings, where the NMDAR blocker ketamine disrupted correlated spiking during SWR. Our results are consistent with a framework in which NMDA receptors both promote activation of SWR events and organize SWR‐associated spiking content. This suggests that, while SWR are short‐lived events emerging in fast excitatory‐inhibitory networks, slower network components including NMDAR‐mediated currents contribute to ripple density and promote consistency in the spiking content across ripples, underpinning mechanisms for fine‐tuning of memory consolidation processes.
more » « less- Award ID(s):
- 1724405
- NSF-PAR ID:
- 10455016
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Hippocampus
- Volume:
- 30
- Issue:
- 12
- ISSN:
- 1050-9631
- Page Range / eLocation ID:
- p. 1356-1370
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Patterns of neural activity that occur spontaneously during sharp-wave ripple (SWR) events in the hippocampus are thought to play an important role in memory formation, consolidation and retrieval. Typical studies examining the content of SWRs seek to determine whether the identity and/or temporal order of cell firing is different from chance. Such ‘first-order’ analyses are focused on a single time point and template (map), and have been used to show, for instance, the existence of preplay. The major methodological challenge in first-order analyses is the construction and interpretation of different chance distributions. By contrast, ‘second-order’ analyses involve a comparison of SWR content between different time points, and/or between different templates. Typical second-order questions include tests of experience-dependence (replay) that compare SWR content before and after experience, and comparisons or replay between different arms of a maze. Such questions entail additional methodological challenges that can lead to biases in results and associated interpretations. We provide an inventory of analysis challenges for second-order questions about SWR content, and suggest ways of preventing, identifying and addressing possible analysis biases. Given evolving interest in understanding SWR content in more complex experimental scenarios and across different time scales, we expect these issues to become increasingly pervasive. This article is part of the Theo Murphy meeting issue ‘Memory reactivation: replaying events past, present and future’.more » « less
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