Activity-Dependent Downscaling of Subthreshold Synaptic Inputs during Slow-Wave-Sleep-like Activity In Vivo.
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ABSTRACT:
SUBMITTER: Gonzalez-Rueda A
PROVIDER: S-EPMC5873548 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
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Project description:Study objectiveIn humans sleep slow wave activity (SWA) declines during adolescence. It has been suggested that this decline reflects the elimination of cortical synapses, but this hypothesis has never been tested directly.DesignWe focused on mouse frontal cortex and collected data from early adolescence (?postnatal day 20, P20) to adulthood (P60) of (1) SWA; (2) expression of synapsin I, a presynaptic marker; and (3) number of dendritic spines in layers I-II.SettingBasic sleep research laboratory.Patients or participantsYFP-line H mice (n = 70; P15-87, all males) and GFP-line S mice (n = 14; P17-60, 8 females) were used for EEG recording. Forty-five YFP mice (P19-119, 12 females) and 42 GFP-S mice (P20-60, 14 females) were used for in vivo 2-photon imaging and ex vivo confocal microscopy, respectively. Other YGP mice (n = 57, P10-77) were used for western blot analysis of synapsin I.InterventionsN/A.Measurements and resultsAs in humans, SWA in mice declined from early adolescence to adulthood. Synapsin I levels increased from P10 to P24, with little change afterwards. Mean spine density in apical dendrites of layer V pyramidal neurons (YFP-H) showed no change from P20 to P60. Spine number in layers I-II apical dendrites, belonging to layer III and V pyramidal neurons (GFP-S), increased slightly from P20 to P30 and decreased from P30 to P60; smaller spines decreased in number from P20 to P60, while bigger spines increased.ConclusionsIn mice, it is unlikely that the developmental decrease in SWA can be accounted for by a net pruning of cortical synapses.
| S-EPMC3972420 | biostudies-literature
Project description:Slow wave sleep (SWS) is associated with spontaneous brain oscillations that are thought to participate in sleep homeostasis and to support the processing of information related to the experiences of the previous awake period. At the cellular level, during SWS, a slow oscillation (<1 Hz) synchronizes firing patterns in large neuronal populations and is reflected on electroencephalography (EEG) recordings as large-amplitude, low-frequency waves. By using simultaneous EEG and event-related functional magnetic resonance imaging (fMRI), we characterized the transient changes in brain activity consistently associated with slow waves (>140 microV) and delta waves (75-140 microV) during SWS in 14 non-sleep-deprived normal human volunteers. Significant increases in activity were associated with these waves in several cortical areas, including the inferior frontal, medial prefrontal, precuneus, and posterior cingulate areas. Compared with baseline activity, slow waves are associated with significant activity in the parahippocampal gyrus, cerebellum, and brainstem, whereas delta waves are related to frontal responses. No decrease in activity was observed. This study demonstrates that SWS is not a state of brain quiescence, but rather is an active state during which brain activity is consistently synchronized to the slow oscillation in specific cerebral regions. The partial overlap between the response pattern related to SWS waves and the waking default mode network is consistent with the fascinating hypothesis that brain responses synchronized by the slow oscillation restore microwake-like activity patterns that facilitate neuronal interactions.
| S-EPMC2567508 | biostudies-literature
Project description:Slow-wave sleep is thought to be important for retuning cortical synapses, but the cellular mechanisms remain unresolved. During slow-wave activity, cortical neurons display synchronized transitions between depolarized Up states and hyperpolarized Down states. Here, using recordings from LIII pyramidal neurons from acute slices of mouse medial entorhinal cortex, we find that subthreshold inputs arriving during the Up state undergo synaptic weakening. This does not reflect a process of global synaptic downscaling, as it is dependent on presynaptic spiking, with network state encoded in the synaptically evoked spine Ca2+ responses. Our data indicate that the induction of synaptic weakening is under postsynaptic control, as it can be prevented by correlated postsynaptic spiking activity, and depends on postsynaptic NMDA receptors and GSK3? activity. This provides a mechanism by which slow-wave activity might bias synapses towards weakening, while preserving the synaptic connections within active neuronal assemblies.Slow oscillations between cortical Up and Down states are a defining feature of deep sleep, but their function is not well understood. Here the authors study Up/Down states in acute slices of entorhinal cortex, and find that Up states promote the weakening of subthreshold synaptic inputs, while suprathreshold inputs are preserved or strengthened.
| S-EPMC5610171 | biostudies-literature
Project description:Sleep slow wave activity (SWA), the major electrophysiological characteristic of deep sleep, mirrors both cortical restructuring and functioning. The incidence of Major Depressive Disorder (MDD) substantially rises during the vulnerable developmental phase of adolescence, where essential cortical restructuring is taking place. The goal of this study was to assess characteristics of SWA topography in adolescents with MDD, in order to assess abnormalities in both cortical restructuring and functioning on a local level. All night high-density EEG was recorded in 15 patients meeting DSM-5 criteria for MDD and 15 sex- and age-matched healthy controls. The actual symptom severity was assessed using the Children's Depression Rating Scale-Revised (CDRS-R). Topographical power maps were calculated based on the average SWA of the first non-rapid eye movement (NREM) sleep episode. Depressed adolescents exhibited significantly more SWA in a cluster of frontal electrodes compared to controls. SWA over frontal brain regions correlated positively with the CDRS-R subscore "morbid thoughts". Self-reported sleep latency was significantly higher in depressed adolescents compared to controls whereas sleep architecture did not differ between the groups. Higher frontal SWA in depressed adolescents may represent a promising biomarker tracing cortical regions of intense use and/or restructuring.
| S-EPMC4712324 | biostudies-literature
Project description:A disruption in the slow wave activity (SWA) mediated synaptic downscaling process features Parkinson's disease (PD) patients presenting levodopa-induced dyskinesia (LID). To corroborate the role of SWA in LID development, 15 PD patients with LID, who underwent a polysomnography before LID's appearance, were included. Slow wave sleep epochs were extracted, combined and segmented into early and late sleep. SWA power was calculated. A linear regression model established that the SWA overnight decrease could predict the time to the emergence of LID. Our finding supports the link between SWA-mediated synaptic downscaling and the development of LID. If confirmed, it could pave the way to the study of possible sleep targeted therapies able to protect PD patients from LID development.
| S-EPMC10509191 | biostudies-literature
Project description:We investigated whether the benefit of slow wave sleep (SWS) for memory consolidation typically observed in healthy individuals is disrupted in people with accelerated long-term forgetting (ALF) due to epilepsy. SWS is thought to play an active role in declarative memory in healthy individuals and, furthermore, electrographic epileptiform activity is often more prevalent during SWS than during wakefulness or other sleep stages. We studied the relationship between SWS and the benefit of sleep for memory retention using a word-pair associates task. In both the ALF and the healthy control groups, sleep conferred a memory benefit. However, the relationship between the amount of SWS and sleep-related memory benefits differed significantly between the groups. In healthy participants, the amount of SWS correlated positively with sleep-related memory benefits. In stark contrast, the more SWS, the smaller the sleep-related memory benefit in the ALF group. Therefore, contrary to its role in healthy people, SWS-associated brain activity appears to be deleterious for memory in patients with ALF.
| S-EPMC5084685 | biostudies-literature
Project description:Slow wave activity (SWA) during sleep is associated with synaptic regulation and memory processing functions. Each cycle of non-rapid-eye-movement (NREM) sleep demonstrates a waxing and waning amount of SWA during the transitions between stages N2 and N3 sleep, and the deeper N3 sleep is associated with an increased density of SWA. Further, SWA is an amalgam of different types of slow waves, each identifiable by their temporal coupling to spindle subtypes with distinct physiological features. The objectives of this study were to better understand the neurobiological properties that distinguish different slow wave and spindle subtypes, and to examine the composition of SWA across cycles of NREM sleep. We further sought to explore changes in the composition of NREM cycles that occur among aging adults. To address these goals, we analyzed subsets of data from two well-characterized cohorts of healthy adults: (1) The DREAMS Subjects Database (n = 20), and (2) The Cleveland Family Study (n = 60). Our analyses indicate that slow wave/spindle coupled events can be characterized as frontal vs. central in their relative distribution between electroencephalography (EEG) channels. The frontal predominant slow waves are identifiable by their coupling to late-fast spindles and occur more frequently during stage N3 sleep. Conversely, the central-associated slow waves are identified by coupling to early-fast spindles and favor occurrence during stage N2 sleep. Together, both types of slow wave/spindle coupled events form the composite of SWA, and their relative contribution to the SWA rises and falls across cycles of NREM sleep in accordance with depth of sleep. Exploratory analyses indicated that older adults produce a different composition of SWA, with a shift toward the N3, frontal subtype, which becomes increasingly predominant during cycles of NREM sleep. Overall, these data demonstrate that subtypes of slow wave/spindle events have distinct cortical propagation patterns and differ in their distribution across lighter vs. deeper NREM sleep. Future efforts to understand how slow wave sleep and slow wave/spindle coupling impact memory performance and neurological disease may benefit from examining the composition of SWA to avoid potential confounds that may occur when comparing dissimilar neurophysiological events.
| S-EPMC9260314 | biostudies-literature
Project description:Fast inhibitory synaptic inputs, which cause conductance changes that typically last for 10-100 ms, participate in the generation and maintenance of cortical rhythms. We show here that these fast events can have influences that outlast the duration of the synaptic potentials by interacting with subthreshold membrane potential oscillations. Inhibitory postsynaptic potentials (IPSPs) in cortical neurons in vitro shifted the oscillatory phase for several seconds. The phase shift caused by two IPSPs or two current pulses summed non-linearly. Cholinergic neuromodulation increased the power of the oscillations and decreased the magnitude of the phase shifts. These results show that the intrinsic conductances of cortical pyramidal neurons can carry information about inhibitory inputs and can extend the integration window for synaptic input.
| S-EPMC2862239 | biostudies-literature
Project description:Neocortical local field potentials have shown that gamma oscillations occur spontaneously during slow-wave sleep (SWS). At the macroscopic EEG level in the human brain, no evidences were reported so far. In this study, by using simultaneous scalp and intracranial EEG recordings in 20 epileptic subjects, we examined gamma oscillations in cerebral cortex during SWS. We report that gamma oscillations in low (30-50 Hz) and high (60-120 Hz) frequency bands recurrently emerged in all investigated regions and their amplitudes coincided with specific phases of the cortical slow wave. In most of the cases, multiple oscillatory bursts in different frequency bands from 30 to 120 Hz were correlated with positive peaks of scalp slow waves ("IN-phase" pattern), confirming previous animal findings. In addition, we report another gamma pattern that appears preferentially during the negative phase of the slow wave ("ANTI-phase" pattern). This new pattern presented dominant peaks in the high gamma range and was preferentially expressed in the temporal cortex. Finally, we found that the spatial coherence between cortical sites exhibiting gamma activities was local and fell off quickly when computed between distant sites. Overall, these results provide the first human evidences that gamma oscillations can be observed in macroscopic EEG recordings during sleep. They support the concept that these high-frequency activities might be associated with phasic increases of neural activity during slow oscillations. Such patterned activity in the sleeping brain could play a role in off-line processing of cortical networks.
| S-EPMC3319559 | biostudies-literature
Project description:BackgroundSlow wave sleep (SWS) plays an important role in neurophysiologic restoration. Experimentally testing the effect of SWS disruption previously required highly time-intensive and subjective methods. Our goal was to develop an automated and objective protocol to reduce SWS without affecting sleep architecture.New methodWe developed a custom Matlab™ protocol to calculate electroencephalogram spectral power every 10s live during a polysomnogram, exclude artifact, and, if measurements met criteria for SWS, deliver increasingly louder tones through earphones. Middle-aged healthy volunteers (n=10) each underwent 2 polysomnograms, one with the SWS disruption protocol and one with sham condition.ResultsThe SWS disruption protocol reduced SWS compared to sham condition, as measured by spectral power in the delta (0.5-4Hz) band, particularly in the 0.5-2Hz range (mean 20% decrease). A compensatory increase in the proportion of total spectral power in the theta (4-8Hz) and alpha (8-12Hz) bands was seen, but otherwise normal sleep features were preserved. N3 sleep decreased from 20±34 to 3±6min, otherwise there were no significant changes in total sleep time, sleep efficiency, or other macrostructural sleep characteristics.Comparison with existing methodThis novel SWS disruption protocol produces specific reductions in delta band power similar to existing methods, but has the advantage of being automated, such that SWS disruption can be performed easily in a highly standardized and operator-independent manner.ConclusionThis automated SWS disruption protocol effectively reduces SWS without impacting overall sleep architecture.
| S-EPMC5399676 | biostudies-literature