Abstract
A period of sleep over the first few hours following single-trial contextual fear conditioning (CFC) is essential for hippocampally-mediated memory consolidation. Recent studies have uncovered intracellular mechanisms required for memory formation which are affected by post-conditioning sleep and sleep deprivation. However, almost nothing is known about the circuit-level activity changes during sleep that underlie activation of these intracellular pathways. Here we continuously recorded from the CA1 region of freely-behaving mice to characterize neuronal and network activity changes occurring during active memory consolidation. C57BL/6J mice were implanted with custom stereotrode recording arrays to monitor activity of individual CA1 neurons, local field potentials (LFPs), and electromyographic activity. Sleep architecture and state-specific CA1 activity patterns were assessed during a 24 h baseline recording period, and for 24 h following either single-trial CFC or Sham conditioning. We find that consolidation of CFC is not associated with significant sleep architecture changes, but is accompanied by long-lasting increases in CA1 neuronal firing, as well as increases in delta, theta, and gamma-frequency CA1 LFP activity. These changes occurred in both sleep and wakefulness, and may drive synaptic plasticity within the hippocampus during memory formation. We also find that functional connectivity within the CA1 network, assessed through functional clustering algorithm (FCA) analysis of spike timing relationships among recorded neurons, becomes more stable during consolidation of CFC. This increase in network stability was not present following Sham conditioning, was most evident during post-CFC slow wave sleep (SWS), and was negligible during post-CFC wakefulness. Thus in the interval between encoding and recall, SWS may stabilize the hippocampal contextual fear memory (CFM) trace by promoting CA1 network stability.
Highlights
Sleep plays an essential role in promoting various forms of memory consolidation (Aton et al, 2009b) and plasticity in brain circuits in vivo (Aton et al, 2009a, 2013, 2014; Seibt et al, 2012)
While contextual fear memory (CFM) consolidation is known to require sleep behavior, neither contextual fear conditioning (CFC) nor Sham conditioning caused significant changes in subsequent sleep architecture (i.e., % of time spent in slow wave sleep (SWS), rapid eye movement (REM), or wakefulness, or mean duration of SWS, REM or wakefulness bouts) from the baseline recording period (Figure 1B)
REM intervals could not be separately assessed due to the relatively brevity and infrequency of REM episodes, which reduced the reliability of stability measurements. These studies were aimed at assessing sleep-associated changes in CA1 network activity that might contribute to the sleepdependence of CFM consolidation
Summary
Sleep plays an essential role in promoting various forms of memory consolidation (Aton et al, 2009b) and plasticity in brain circuits in vivo (Aton et al, 2009a, 2013, 2014; Seibt et al, 2012). CFM consolidation requires both CA1 network activity (Daumas et al, 2005), and the activation of kinase and protein synthesis pathways (Bourtchouladze et al, 1998; Lattal and Abel, 2004; Sindreu et al, 2007), in the hours immediately following CFC. Because these pathways are required for CA1 LTP, one possibility is that sleep interferes with CFM consolidation by disrupting synaptic potentiation in CA1. The pathways disrupted in the hippocampus by sleep loss (e.g., mTOR-mediated activation of protein synthesis, kinasemediated protein phosphorylation) are essential for CA1 LTP (Vecsey et al, 2009, 2012), and critically, sleep deprivation itself
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