CA1 hippocampal network activity changes during sleep-dependent memory consolidation

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.

Network resonance during slow-wave sleep facilitates memory consolidation through phase-coding

“…This suggests that locking of neuronal firing with network oscillations, and associated stabilization of network functional connectivity patterns, is driven by synaptic potentiation between engram neurons and other neurons in the network. This agrees with previous experimental results, showing that contextual fear memory consolidation is associated with both increased theta-band oscillations, and increased FuNS, during sleep in the hours immediately following conditioning (17,18,20).…”

“…C57BL/6J mice implanted with bundles of CA1 stereotrodes either underwent CFC (placement into a novel environmental context, followed 2.5 min later by a 2-s, 0.75 mA foot shock; n = 5 mice), sham conditioning (placement in a novel context without foot shock; Sham; n = 3 mice), or CFC followed by 6 h of sleep deprivation (a manipulation known to disrupt fear memory consolidation [18,19,27]; SD; n = 5 mice) ( Figure 2 ). Spike data from individual neurons was discriminated offline using standard methods (consistent waveform shape and amplitude on the two stereotrode wires, relative cluster position of spike waveforms in principle component space, ISI ≥ 1 ms) (5,17,18,20,28). Only neurons that were stably recorded and reliably discriminated throughout the entire baseline and post-conditioning period were included in subsequent analyses of network dynamics.…”

“…Contextual fear conditioning (CFC) leads to rapid formation and consolidation of new memories (i.e. after single-trial learning) (17). CFM consolidation relies on ad lib sleep in the hours immediately following CFC (18,19), and is associated with augmented theta-frequency activity in CA1 in the hours following CFC (20).…”

Sevoflurane anesthesia induces neither contextual fear memory impairment nor alterations in local population connectivity of medial prefrontal cortex local field potentials networks in aged rats

“…Tsujimoto et al [50,51] showed that theta oscillations were observed in the PFC, both in the local field potential and in the spiking of single neurons in a monkey self-initiated hand movement task. Ognjanovski [52] had reported that functional connectivity of spike timing relationships among recorded neurons within the CA1 network became more stable during consolidation of mice con-textual fear conditioning. Theta oscillations are also very important component of the interaction between the prefrontal cortex and the hippocampus and are also the carrier of functional networks linking the mPFC with the basolateral amygdala during contextual fear conditioning memory [53][54][55].…”

“…Theta oscillation has been suggested to support of a neural code [49], especially in PFC and in hippocampus. Ognjanovski [52] had reported that functional connectivity of spike timing relationships among recorded neurons within the CA1 network became more stable during consolidation of mice con-textual fear conditioning. Tsujimoto et al [50,51] showed that theta oscillations were observed in the PFC, both in the local field potential and in the spiking of single neurons in a monkey self-initiated hand movement task.…”