- Award ID(s):
- 2015276
- NSF-PAR ID:
- 10422634
- Date Published:
- Journal Name:
- eLife
- Volume:
- 11
- ISSN:
- 2050-084X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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null (Ed.)Sleep has many roles, from strengthening new memories to regulating mood and appetite. While we might instinctively think of sleep as a uniform state of reduced brain activity, the reality is more complex. First, over the course of the night, we cycle between a number of different sleep stages, which reflect different levels of sleep depth. Second, the amount of sleep depth is not necessarily even across the brain but can vary between regions. These sleep stages consist of either rapid eye movement (REM) sleep or non-REM (NREM) sleep. REM sleep is when most dreaming occurs, whereas NREM sleep is particularly important for learning and memory and can vary in duration and depth. During NREM sleep, large groups of neurons synchronize their firing to create rhythmic waves of activity known as slow waves. The more synchronous the activity, the deeper the sleep. Vaidyanathan et al. now show that brain cells called astrocytes help regulate NREM sleep. Astrocytes are not neurons but belong to a group of specialized cells called glia. They are the largest glia cell type in the brain and display an array of proteins on their surfaces called G-protein-coupled receptors (GPCRs). These enable them to sense sleep-wake signals from other parts of the brain and to generate their own signals. In fact, each astrocyte can communicate with thousands of neurons at once. They are therefore well-poised to coordinate brain activity during NREM sleep. Using innovative tools, Vaidyanathan et al. visualized astrocyte activity in mice as the animals woke up or fell asleep. The results showed that astrocytes change their activity just before each sleep–wake transition. They also revealed that astrocytes control both the depth and duration of NREM sleep via two different types of GPCR signals. Increasing one of these signals (Gi-GPCR) made the mice sleep more deeply but did not change sleep duration. Decreasing the other (Gq-GPCR) made the mice sleep for longer but did not affect sleep depth. Sleep problems affect many people at some point in their lives, and often co-exist with other conditions such as mental health disorders. Understanding how the brain regulates different features of sleep could help us develop better – and perhaps more specific – treatments for sleep disorders. The current study suggests that manipulating GPCRs on astrocytes might increase sleep depth, for example. But before work to test this idea can begin, we must first determine whether findings from sleeping mice also apply to people.more » « less
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Differential thalamocortical interactions in slow and fast spindle generation: A computational modelCymbalyuk, Gennady S. (Ed.)
Cortical slow oscillations (SOs) and thalamocortical sleep spindles are two prominent EEG rhythms of slow wave sleep. These EEG rhythms play an essential role in memory consolidation. In humans, sleep spindles are categorized into slow spindles (8–12 Hz) and fast spindles (12–16 Hz), with different properties. Slow spindles that couple with the up-to-down phase of the SO require more experimental and computational investigation to disclose their origin, functional relevance and most importantly their relation with SOs regarding memory consolidation. To examine slow spindles, we propose a biophysical thalamocortical model with two independent thalamic networks (one for slow and the other for fast spindles). Our modeling results show that fast spindles lead to faster cortical cell firing, and subsequently increase the amplitude of the cortical local field potential (LFP) during the SO down-to-up phase. Slow spindles also facilitate cortical cell firing, but the response is slower, thereby increasing the cortical LFP amplitude later, at the SO up-to-down phase of the SO cycle. Neither the SO rhythm nor the duration of the SO down state is affected by slow spindle activity. Furthermore, at a more hyperpolarized membrane potential level of fast thalamic subnetwork cells, the activity of fast spindles decreases, while the slow spindles activity increases. Together, our model results suggest that slow spindles may facilitate the initiation of the following SO cycle, without however affecting expression of the SO Up and Down states.
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Abstract 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.
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Abstract Study Objectives Synchronization of neural activity within local networks and between brain regions is a major contributor to rhythmic field potentials such as the EEG. On the other hand, dynamic changes in microstructure and activity are reflected in the EEG, for instance slow oscillation (SO) slope can reflect synaptic strength. SO-spindle coupling is a measure for neural communication. It was previously associated with memory consolidation, but also shown to reveal strong interindividual differences. In studies, weak electric current stimulation has modulated brain rhythms and memory retention. Here, we investigate whether SO-spindle coupling and SO slope during baseline sleep are associated with (predictive of) stimulation efficacy on retention performance. Methods Twenty-five healthy subjects participated in three experimental sessions. Sleep-associated memory consolidation was measured in two sessions, in one anodal transcranial direct current stimulation oscillating at subjects individual SO frequency (so-tDCS) was applied during nocturnal sleep. The third session was without a learning task (baseline sleep). The dependence on SO-spindle coupling and SO-slope during baseline sleep of so-tDCS efficacy on retention performance were investigated. Results Stimulation efficacy on overnight retention of declarative memories was associated with nesting of slow spindles to SO trough in deep nonrapid eye movement baseline sleep. Steepness and direction of SO slope in baseline sleep were features indicative for stimulation efficacy. Conclusions Findings underscore a functional relevance of activity during the SO up-to-down state transition for memory consolidation and provide support for distinct consolidation mechanisms for types of declarative memories.more » « less
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REM sleep is important for the processing of emotional memories, including fear memories. Rhythmic interactions, especially in the theta band, between the medial prefrontal cortex (mPFC) and limbic structures are thought to play an important role, but the ways in which memory processing occurs at a mechanistic and circuits level are largely unknown. To investigate how rhythmic interactions lead to fear extinction during REM sleep, we used a biophysically based model that included the infralimbic cortex (IL), a part of the mPFC with a critical role in suppressing fear memories. Theta frequency (4–12 Hz) inputs to a given cell assembly in IL, representing an emotional memory, resulted in the strengthening of connections from the IL to the amygdala and the weakening of connections from the amygdala to the IL, resulting in the suppression of the activity of fear expression cells for the associated memory. Lower frequency (4 Hz) theta inputs effected these changes over a wider range of input strengths. In contrast, inputs at other frequencies were ineffective at causing these synaptic changes and did not suppress fear memories. Under post-traumatic stress disorder (PTSD) REM sleep conditions, rhythmic activity dissipated, and 4 Hz theta inputs to IL were ineffective, but higher-frequency (10 Hz) theta inputs to IL induced changes similar to those seen with 4 Hz inputs under normal REM sleep conditions, resulting in the suppression of fear expression cells. These results suggest why PTSD patients may repeatedly experience the same emotionally charged dreams and suggest potential neuromodulatory therapies for the amelioration of PTSD symptoms. SIGNIFICANCE STATEMENT Rhythmic interactions in the theta band between the mPFC and limbic structures are thought to play an important role in processing emotional memories, including fear memories, during REM sleep. The infralimbic cortex (IL) in the mPFC is thought to play a critical role in suppressing fear memories. We show that theta inputs to the IL, unlike other frequency inputs, are effective in producing synaptic changes that suppress the activity of fear expression cells associated with a given memory. Under PTSD REM sleep conditions, lower-frequency (4 Hz) theta inputs to the IL do not suppress the activity of fear expression cells associated with the given memory but, surprisingly, 10 Hz inputs do. These results suggest potential neuromodulatory therapies for PTSD.more » « less