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Sleep has a complex microarchitecture, encompassing micro-arousals, sleep spindles, and transitions between sleep stages. Fragmented sleep impairs memory consolidation, whereas spindle- and delta-rich NREM sleep and REM sleep promote it. Yet, the relationship between micro-arousals and memory-promoting aspects of sleep remains unclear. We here use fiber photometry in mice to examine how release of the arousal mediator, norepinephrine (NE), shapes sleep microarchitecture. We show that micro-arousals are generated in a periodic pattern during NREM sleep, riding on the peak of locus coeruleus-generated infraslow oscillations of extracellular NE, whereas descending phases of NE oscillations drive spindles. The amplitude of NE oscillations is crucial for shaping sleep microarchitecture related to memory performance: prolonged descent of NE promotes spindle-enriched intermediate state and REM sleep but also associates with awakenings, whereas shorter NE descents uphold NREM sleep and micro-arousals. Thus, the NE oscillatory amplitude may be a target for improving sleep in sleep disorders.

International audience; Sleep is essential for the regulation of neural dynamics and animal behavior. In particular, sleep is crucial for memory consolidation and emotional regulation. In turn, emotions are key to the modulation of learning processes in which sleep also plays a crucial role. Emotional processing triggers coordinated activity between neuronal populations embedded in a network including the hippocampus, amygdala and prefrontal cortex. The optogenetic modulation of these distributed engrams' activity interferes with emotional memory. During non-REM sleep, cross-structure coordinated replay may underpin the consolidation of brain-wide emotional associative engrams. Fear conditioning induces neural synchronization between the amygdala, hippocampus, and medial prefrontal cortex during subsequent REM sleep, the perturbation of which interferes with fear memory consolidation. Future work may focus on the differential mechanisms during REM vs non-REM sleep that underpin emotional regulation and memory consolidation, as well as on distinguishing between these two tightly linked cognitive processes.

Sleep is crucial for healthy cognition, including memory. The two main phases of sleep, REM (rapid eye movement) and non-REM sleep, are associated with characteristic electrophysiological patterns that are recorded using surface and intracranial electrodes. These patterns include sharp-wave ripples, cortical slow oscillations, delta waves, and spindles during non-REM sleep and theta oscillations during REM sleep. They reflect the precisely timed activity of underlying neural circuits. Here, we review how these electrical signatures have been guiding our understanding of the circuits and processes sustaining memory consolidation during sleep, focusing on hippocampal theta oscillations and sharp-wave ripples and how they coordinate with cortical patterns. Finally, we highlight how these brain patterns could also sustain sleep-dependent homeostatic processes and evoke several potential future directions for research on the memory function of sleep., [Figure: see text].

Neuronal firing patterns have significant spatiotemporal variability with no agreed upon theoretical framework. Using a combined experimental and modeling approach, we found that spike interval statistics can be described by discrete modes of activity. Of these, a “ground state” (GS) mode of low-rate spiking is universal among forebrain excitatory neurons and characterized by irregular spiking at neuron-specific rates. In contrast, “activated state” (AS) modes consist of spiking at characteristic timescales and regularity that are specific to neuron populations in a given region and brain state. The majority of spiking is contributed by GS mode, while neurons can transiently switch to AS spiking in response to stimuli or in coordination with population activity patterns. We hypothesize that GS spiking serves to maintain a persistent backbone of neuronal activity while AS modes support communication functions.

Memory consolidation is thought to involve a hippocampo-cortical dialog during sleep to stabilize labile memory traces for long-term storage. However, direct evidence supporting this hypothesis is lacking. We dynamically manipulated the temporal coordination between the two structures during sleep following training on a spatial memory task specifically designed to trigger encoding, but not memory consolidation. Reinforcing the endogenous coordination between hippocampal sharp wave-ripples, cortical delta waves and spindles by timed electrical stimulation resulted in a reorganization of prefrontal cortical networks, along with subsequent increased prefrontal responsivity to the task and high recall performance on the next day, contrary to control rats, which performed at chance levels. Our results provide, to the best of our knowledge, the first direct evidence for a causal role of a hippocampo-cortical dialog during sleep in memory consolidation, and indicate that the underlying mechanism involves a fine-tuned coordination between sharp wave-ripples, delta waves and spindles.

The consolidation of context-dependent emotional memory requires communication between the hippocampus and the basolateral amygdala (BLA), but the mechanisms of this process are unknown. We recorded neuronal ensembles in the hippocampus and BLA while rats learned the location of an aversive air puff on a linear track, as well as during sleep before and after training. We found coordinated reactivations between the hippocampus and the BLA during non-REM sleep following training. These reactivations peaked during hippocampal sharp wave-ripples (SPW-Rs) and involved a subgroup of BLA cells positively modulated during hippocampal SPW-Rs. Notably, reactivation was stronger for the hippocampus-BLA correlation patterns representing the run direction that involved the air puff than for the 'safe' direction. These findings suggest that consolidation of contextual emotional memory occurs during ripple-reactivation of hippocampus-amygdala circuits.

Consolidation is the process by which recently acquired memories are gradually strengthened and reorganized for long-term storage, potentially involving a transfer from the hippocampus to cortical areas. Hippocampal sharp-wave ripples (SPWRs) are transient fast oscillations (200 Hz) occurring during slow-wave sleep, rest, and short immobility periods. Because place cells are sequentially reactivated during SPWRs, and because their frequency would be propitious to induce long-term potentiation, SPWRs have been considered a likely candidate mechanism for spatial learning and memory consolidation. Establishing a causal link between the two requires closed-loop interventional experiments where SPWRs are detected online and suppressed in a spatiotemporally selective manner. This was achieved in three studies where SPWRs were suppressed either during sleep and rest following training on a spatial task or during training on the spatial task. The resulting impairments in performance in all three studies established for the first time a causal link between sleep and rest SPWRs and memory consolidation on the one hand, and awake SPWRs and working spatial memory on the other hand. These studies also raised the question of a differential role for awake and sleep/rest ripples that will require further investigation. Similarly, conclusive evidence for a role of SPWRs in hippocampo-cortical information transfer remains elusive.

Hippocampal cell assemblies coding for past, present and future events form theta-timescale (~100 ms) sequences that represent spatio-temporal episodes. However, the underlying mechanisms remain largely unknown. We recorded hippocampal and entorhinal cortical activity as rats experienced backward travel on a model train. Although the firing fields of place cells remained stable, the order in which they were activated in the theta sequence was reversed during backward travel. Thus, hippocampal cell assemblies coordinated their relative timing to correctly predict the sequential traversal of place fields in reverse order. At the single-cell level, theta phase represented distance traveled through the field, even though the head of the rat was oriented opposite to travel direction and entorhinal head-direction cells maintained their preferred firing direction. Our results challenge most theoretical models of theta sequence generation in the hippocampus.

Hippocampal sharp wave-ripples (SPW-Rs) and associated place-cell reactivations are crucial for spatial memory consolidation during sleep and rest. However, it remains unclear how learning and consolidation requirements influence and regulate subsequent SPW-R activity. Indeed, SPW-R activity has been observed not only following complex behavioral tasks, but also after random foraging in familiar environments, despite markedly different learning requirements. Because transient increases in SPW-R rates have been reported following training on memory tasks, we hypothesized that SPW-R activity following learning (but not routine behavior) could involve specific regulatory processes related to ongoing consolidation. Interfering with ripples would then result in a dynamic compensatory response only when initial memory traces required consolidation. Here we trained rats on a spatial memory task, and showed that subsequent sleep periods where ripple activity was perturbed by timed electrical stimulation were indeed characterized by increased SPW-R occurrence rates compared with control sleep periods where stimulations were slightly delayed in time and did not interfere with ripples. Importantly, this did not occur following random foraging in a familiar environment. We next showed that this dynamic response was abolished following injection of an NMDA receptor blocker (MK-801) before, but not after training. Our results indicate that NMDA receptor-dependent processes occurring during learning, such as network “tagging” and plastic changes, regulate subsequent ripple-mediated consolidation of spatial memory during sleep.

This work presents a new fabrication technology for silicon-based neural probe devices and their assembly into two-dimensional (2D) as well as three-dimensional (3D) microprobe arrays for neural recording. The fabrication is based on robust double-sided deep reactive ion etching of standard silicon wafers and allows full 3D control of the probe geometry. Wafer level electroplating of gold pads was performed to improve the 3D assembly into a platform. Lithography-based probe-tracking features for quality management were introduced. Probes for two different assembly methods, namely direct bonding to a flexible micro-cable and platform-based out-of-plane interconnection, were produced. Systems for acute and sub-chronic recordings were assembled and characterized. Recordings from rats demonstrated the recording capability of these devices.

International audience; Sharp wave-ripple (SPW-R) complexes in the hippocampus-entorhinal cortex are believed to be important for transferring labile memories from the hippocampus to the neocortex for long-term storage. We found that selective elimination of SPW-Rs during post-training consolidation periods resulted in performance impairment in rats trained on a hippocampus-dependent spatial memory task. Our results provide evidence for a prominent role of hippocampal SPW-Rs in memory consolidation.

Gabrielle Girardeau, Michaël B. Zugaro et Sidney I. Wiener © P. Imbert, Collège de France Karim Benchenane György Buzsáki, professeur à Rutgers University, Newark, USA, a donné une série de conférences au Collège de France en juin 2008, en tant que professeur invité. On connaît depuis longtemps l’importance du sommeil pour les fonctions cognitives, et notamment pour la mémoire. Cependant les mécanismes en jeu commencent à peine à être élucidés. De nombreuses études ont déjà montré que l’hi...