The most prominent EEG events in sleep are slow waves, reflecting a slow (<1 Hz) oscillation between up and down states in cortical neurons. It is unknown whether slow oscillations are synchronous across the majority or the minority of brain regions—are they a global or local phenomenon? To examine this, we recorded simultaneously scalp EEG, intracerebral EEG, and unit firing in multiple brain regions of neurosurgical patients. We find that most sleep slow waves and the underlying active and inactive neuronal states occur locally. Thus, especially in late sleep, some regions can be active while others are silent. We also find that slow waves can propagate, usually from medial prefrontal cortex to the medial temporal lobe and hippocampus. Sleep spindles, the other hallmark of NREM sleep EEG, are likewise predominantly local. Thus, intracerebral communication during sleep is constrained because slow and spindle oscillations often occur out-of-phase in different brain regions.
The work of Mircea Steriade demonstrated that the neocortex could synchronize large regions of the thalamus within 10–100 milliseconds (for review see Steriade and Timofeev, 2003, Steriade, 2005). Unlike the synchrony generated by the cortex, the retinal afferents synchronize a restricted group of neighboring thalamic neurons with <1-millisecond precision (Alonso et al., 1996, Yeh et al., 2003). Here, we use a large sample (n= 372) of simultaneous recordings from neighboring neurons in the Lateral Geniculate Nucleus (LGN) to illustrate the high specificity of the synchrony generated by retinal afferents and its dependency on sensory stimulation. First, we demonstrate that cells sharing a retinal afferent show a balanced receptive field diversity: while slight receptive field mismatches are common, the largest mismatches in a specific property (e.g. receptive field size) are restricted to cells that are precisely matched in other properties (e.g. receptive field overlap). Second, we show that these receptive field mismatches are functionally important and can lead to a 5-fold variation in the percentage of synchronous spikes driven by the shared retinal afferent under different stimulus conditions. Based on these and other findings, we speculate that the precise synchronous firing of cells sharing a retinal afferent could serve to amplify local stimuli that may be too brief and small to generate a large number of thalamic spikes.
LGN; retinogeniculate; correlated firing; visual cortex; spike timing; thalamocortical
In slow neocortical paroxysmal oscillations, the de- and hyperpolarizing envelopes in neocortical neurons are large compared with slow sleep oscillations. Increased local synchrony of membrane potential oscillations during seizure is reflected in larger electroencephalographic oscillations and the appearance of spike- or polyspike-wave complex recruitment at 2- to 3-Hz frequencies. The oscillatory mechanisms underlying this paroxysmal activity were investigated in computational models of cortical networks. The extracellular K+ concentration ([K+]o) was continuously computed based on neuronal K+ currents and K+ pumps as well as glial buffering. An increase of [K+]o triggered a transition from normal awake-like oscillations to 2- to 3-Hz seizure-like activity. In this mode, the cells fired periodic bursts and nearby neurons oscillated highly synchronously; in some cells depolarization led to spike inactivation lasting 50–100 ms. A [K+]o increase, sufficient to produce oscillations could result from excessive firing (e.g., induced by external stimulation) or inability of K+ regulatory system (e.g., when glial buffering was blocked). A combination of currents including high-threshold Ca2+, persistent Na+ and hyperpolarization-activated depolarizing (Ih) currents was sufficient to maintain 2- to 3-Hz activity. In a network model that included lateral K+ diffusion between cells, increase of [K+]o in a small region was generally sufficient to maintain paroxysmal oscillations in the whole network. Slow changes of [K+]o modulated the frequency of bursting and, in some case, led to fast oscillations in the 10- to 15-Hz frequency range, similar to the fast runs observed during seizures in vivo. These results suggest that modifications of the intrinsic currents mediated by increase of [K+]o can explain the range of neocortical paroxysmal oscillations in vivo.
Large amplitude slow waves are characteristic for the summary brain activity, recorded as electroencephalogram (EEG) or local field potentials (LFP), during deep stages of sleep and some types of anesthesia. Slow rhythm of the synchronized EEG reflects an alternation of active (depolarized, UP) and silent (hyperpolarized, DOWN) states of neocortical neurons. In neurons, involvement in the generalized slow oscillation results in a long-range synchronization of changes of their membrane potential as well as their firing. Here, we aimed at intracellular analysis of details of this synchronization. We asked which components of neuronal activity exhibit long-range correlations during the synchronized EEG? To answer this question, we made simultaneous intracellular recordings from two to four neocortical neurons in cat neocortex. We studied how correlated is the occurrence of active and silent states, and how correlated are fluctuations of the membrane potential in pairs of neurons located close one to the other or separated by up to 13 mm. We show that strong long-range correlation of the membrane potential was observed only (i) during the slow oscillation but not during periods without the oscillation, (ii) during periods which included transitions between the states but not during within-the-state periods, and (iii) for the low-frequency (<5 Hz) components of membrane potential fluctuations but not for the higher-frequency components (>10 Hz). In contrast to the neurons located several millimeters one from the other, membrane potential fluctuations in neighboring neurons remain strongly correlated during periods without slow oscillation. We conclude that membrane potential correlation in distant neurons is brought about by synchronous transitions between the states, while activity within the states is largely uncorrelated. The lack of the generalized fine-scale synchronization of membrane potential changes in neurons during the active states of slow oscillation may allow individual neurons to selectively engage in short living episodes of correlated activity—a process that may be similar to dynamical formation of neuronal ensembles during activated brain states.
intracellular recording; cat; sleep; synchrony
Slow waves and sleep spindles are the two main oscillations occurring during NREM sleep. While slow oscillations are primarily generated and modulated by the cortex, sleep spindles are initiated by the thalamic reticular nucleus (TRN), and regulated by thalamo-reticular and thalamo-cortical circuits. In a recent high-density electroencephalographic (hd-EEG) study we found that 18 medicated schizophrenics had reduced sleep spindles compared to healthy and depressed subjects during the first NREM episode. Here we investigated whether spindle deficits were: a) present in a larger sample of schizophrenic patients; b) consistent across the night; c) related to antipsychotic medications; d) suggestive of impairments in specific neuronal circuits. Whole night hd-EEG recordings were performed in 49 schizophrenics, 20 non-schizophrenic patients on antipsychotics and 44 healthy subjects. In addition to sleep spindles, several parameters of slow waves were assessed. Schizophrenics had whole-night deficits in spindle power (12–16 Hz) and in slow (12–14 Hz) and fast (14–16 Hz) spindle amplitude, duration, number and integrated spindle activity (ISA) in prefrontal, centroparietal and temporal regions. ISA and spindle number had the largest effect sizes (ES≥2.21). By contrast, no slow wave deficits were found in schizophrenics. These results indicate that spindle deficits i) can be reliably established in schizophrenics, ii) are stable across the night, iii) are unlikely to be due to antipsychotic medications, and iv) point to deficits in TRN and thalamo-reticular circuits.
The state of non-REM sleep (NREM), or slow wave sleep, is associated with a synchronized EEG pattern in which sleep spindles and/or K complexes and high-voltage slow wave activity (SWA) can be recorded over the entire cortical surface. In humans, NREM is subdivided into stages 2 and 3–4 (presently named N3) depending on the proportions of each of these polygraphic events. NREM is necessary for normal physical and intellectual performance and behavior. An overview of the brain structures involved in NREM generation shows that the thalamus and the cerebral cortex are absolutely necessary for the most significant bioelectric and behavioral events of NREM to be expressed; other structures like the basal forebrain, anterior hypothalamus, cerebellum, caudal brain stem, spinal cord and peripheral nerves contribute to NREM regulation and modulation. In NREM stage 2, sustained hyperpolarized membrane potential levels resulting from interaction between thalamic reticular and projection neurons gives rise to spindle oscillations in the membrane potential; the initiation and termination of individual spindle sequences depends on corticothalamic activities. Cortical and thalamic mechanisms are also involved in the generation of EEG delta SWA that appears in deep stage 3–4 (N3) NREM; the cortex has classically been considered to be the structure that generates this activity, but delta oscillations can also be generated in thalamocortical neurons. NREM is probably necessary to normalize synapses to a sustainable basal condition that can ensure cellular homeostasis. Sleep homeostasis depends not only on the duration of prior wakefulness but also on its intensity, and sleep need increases when wakefulness is associated with learning. NREM seems to ensure cell homeostasis by reducing the number of synaptic connections to a basic level; based on simple energy demands, cerebral energy economizing during NREM sleep is one of the prevalent hypotheses to explain NREM homeostasis.
slow wave sleep; sleep need; thalamus–cerebral cortex unit; rostral hypnogenic system; caudal hypnogenic system; NREM sleep homeostasis
The slow (<1 Hz) rhythm, the most significant EEG signature of non-rapid eye movement (NREM) sleep, is generally viewed as originating exclusively from neocortical networks. Here we argue that the full manifestation of this fundamental sleep oscillation within a corticothalamic module requires the dynamic interaction of three cardinal oscillators: a predominantly synaptically-based cortical oscillator and two intrinsic, conditional thalamic oscillators. The functional implications of this hypothesis are discussed in relation to other key EEG features of NREM sleep, with respect to coordinating activities in local and distant neuronal assemblies and in the context of facilitating cellular and network plasticity during slow wave sleep.
During non-rapid eye movement (NREM) sleep synchronous neural oscillations between neural silence (down state) and neural activity (up state) occur. Sleep Slow Oscillations (SSOs) events are their EEG correlates. Each event has an origin site and propagates sweeping the scalp. While recent findings suggest a SSO key role in memory consolidation processes, the structure and the propagation of individual SSO events, as well as their modulation by sleep stages and cortical areas have not been well characterized so far.
We detected SSO events in EEG recordings and we defined and measured a set of features corresponding to both wave shapes and event propagations. We found that a typical SSO shape has a transition to down state, which is steeper than the following transition from down to up state. We show that during SWS SSOs are larger and more locally synchronized, but less likely to propagate across the cortex, compared to NREM stage 2. Also, the detection number of SSOs as well as their amplitudes and slopes, are greatest in the frontal regions. Although derived from a small sample, this characterization provides a preliminary reference about SSO activity in healthy subjects for 32-channel sleep recordings.
This work gives a quantitative picture of spontaneous SSO activity during NREM sleep: we unveil how SSO features are modulated by sleep stage, site of origin and detection location of the waves. Our measures on SSOs shape indicate that, as in animal models, onsets of silent states are more synchronized than those of neural firing. The differences between sleep stages could be related to the reduction of arousal system activity and to the breakdown of functional connectivity. The frontal SSO prevalence could be related to a greater homeostatic need of the heteromodal association cortices.
In a recent series of experiments, we demonstrated that a visuomotor adaptation task, 12 hours of left arm immobilization, and rapid transcranial magnetic stimulation (rTMS) during waking can each induce local changes in the topography of electroencephalographic (EEG) slow wave activity (SWA) during subsequent non-rapid eye movement (NREM) sleep. However, the poor spatial resolution of EEG and the difficulty of relating scalp potentials to the activity of the underlying cortex limited the interpretation of these results. In order to better understand local cortical regulation of sleep, we used source modeling to show that plastic changes in specific cortical areas during waking produce correlated changes in SWA during sleep in those same areas. We found that implicit learning of a visuomotor adaptation task induced an increase in SWA in right premotor and sensorimotor cortices when compared to a motor control. These same areas have previously been shown to be selectively involved in the performance of this task. We also found that arm immobilization resulted in a decrease in SWA in sensorimotor cortex. Inducing cortical potentiation with repetitive transcranial magnetic stimulation (rTMS) caused an increase in SWA in the targeted area and a decrease in SWA in the contralateral cortex. Finally, we report the first evidence that these modulations in SWA may be related to the dynamics of individual slow waves. We conclude that there is a local, plasticity dependent component to sleep regulation and confirm previous inferences made from the scalp data.
Sleep slow waves are the main phenomenon underlying NREM sleep. They are homeostatically regulated, they are thought to be linked to learning and plasticity processes and, at the same time, they are associated with marked changes in cortical information processing. Using transcranial magnetic stimulation (TMS) and high-density (hd) EEG we can measure slow waves, induce/measure plastic changes in the cerebral cortex and we can directly assess cortico-cortical information transmission. In this manuscript we review the results of recent experiments in which TMS/hd-EEG is used to demonstrate (i) a causal link between cortical plastic changes and sleep slow waves and (ii) a causal link between slow waves and the decreased ability of thalamocortical circuits to integrate information and to generate conscious experience during NREM sleep. The data presented here suggest a unifying mechanism linking slow waves, plasticity and cortical information integration; moreover, they suggest that TMS can be used as a non-pharmacological mean to controllably induce slow waves in the human cerebral cortex.
sleep homeostasis; synaptic plasticity; consciousness; slow oscillations; bistability
Deep anesthesia is commonly used as a model of slow-wave sleep (SWS). Ketamine-xylazine anesthesia reproduces the main features of sleep slow oscillation: slow, large amplitude waves in field potential, which are generated by the alternation of hyperpolarized and depolarized states of cortical neurons. However, direct quantitative comparison of field potential and membrane potential fluctuations during natural sleep and anesthesia is lacking, so it remains unclear how well the properties of sleep slow oscillation are reproduced by the ketamine-xylazine anesthesia model. Here, we used field potential and intracellular recordings in different cortical areas in the cat, to directly compare properties of slow oscillation during natural sleep and ketamine-xylazine anesthesia. During SWS cortical activity showed higher power in the slow/delta (0.1-4 Hz) and spindle (8-14 Hz) frequency range, while under anesthesia the power in the gamma band (30-100 Hz) was higher. During anesthesia, slow waves were more rhythmic and more synchronous across the cortex. Intracellular recordings revealed that silent states were longer and the amplitude of membrane potential around transition between active and silent states was bigger under anesthesia. Slow waves were largely uniform across cortical areas under anesthesia, but in SWS they were most pronounced in associative and visual areas, but smaller and less regular in somatosensory and motor cortices. We conclude that although the main features of the slow oscillation in sleep and anesthesia appear similar, multiple cellular and network features are differently expressed during natural SWS as compared to ketamine-xylazine anesthesia.
Sleep; oscillations; synchrony; intracellular; anesthesia; ketamine-Xylazine
The need to sleep grows with the duration of wakefulness and dissipates with time spent asleep, a process called sleep homeostasis. What are the consequences of staying awake on brain cells, and why is sleep needed? Surprisingly, we do not know whether the firing of cortical neurons is affected by how long an animal has been awake or asleep. Here we found that after sustained wakefulness cortical neurons fire at higher frequencies in all behavioral states. During early NREM sleep after sustained wakefulness, periods of population activity (ON) are short, frequent, and associated with synchronous firing, while periods of neuronal silence are long and frequent. After sustained sleep, firing rates and synchrony decrease, while the duration of ON periods increases. Changes in firing patterns in NREM sleep correlate with changes in slow-wave-activity, a marker of sleep homeostasis. Thus, the systematic increase of firing during wakefulness is counterbalanced by staying asleep.
slow wave sleep; slow oscillations; EEG; rat; cerebral cortex; multi-unit recording
Brain recovery after prolonged wakefulness is characterized by increased density, amplitude and slope of slow waves (SW, <4 Hz) during non-rapid eye movement (NREM) sleep. These SW comprise a negative phase, during which cortical neurons are mostly silent, and a positive phase, in which most neurons fire intensively. Previous work showed, using EEG spectral analysis as an index of cortical synchrony, that Morning-types (M-types) present faster dynamics of sleep pressure than Evening-types (E-types). We thus hypothesized that single SW properties will also show larger changes in M-types than in E-types in response to increased sleep pressure. SW density (number per minute) and characteristics (amplitude, slope between negative and positive peaks, frequency and duration of negative and positive phases) were compared between chronotypes for a baseline sleep episode (BL) and for recovery sleep (REC) after two nights of sleep fragmentation. While SW density did not differ between chronotypes, M-types showed higher SW amplitude and steeper slope than E-types, especially during REC. SW properties were also averaged for 3 NREM sleep periods selected for their decreasing level of sleep pressure (first cycle of REC [REC1], first cycle of BL [BL1] and fourth cycle of BL [BL4]). Slope was significantly steeper in M-types than in E-types in REC1 and BL1. SW frequency was consistently higher and duration of positive and negative phases constantly shorter in M-types than in E-types. Our data reveal that specific properties of cortical synchrony during sleep differ between M-types and E-types, although chronotypes show a similar capacity to generate SW. These differences may involve 1) stable trait characteristics independent of sleep pressure (i.e., frequency and durations) likely linked to the length of silent and burst-firing phases of individual neurons, and 2) specific responses to increased sleep pressure (i.e., slope and amplitude) expected to depend on the synchrony between neurons.
Cortical synchronization during NREM sleep, characterized by electroencephalographic slow waves (SW <4Hz and >75 µV), is strongly related to the number of hours of wakefulness prior to sleep and to the quality of the waking experience. Whether a similar increase in wakefulness length leads to a comparable enhancement in NREM sleep cortical synchronization in young and older subjects is still a matter of debate in the literature. Here we evaluated the impact of 25-hours of wakefulness on SW during a daytime recovery sleep episode in 29 young (27y ±5), and 34 middle-aged (51y ±5) subjects. We also assessed whether age-related changes in NREM sleep cortical synchronization predicts the ability to maintain sleep during daytime recovery sleep. Compared to baseline sleep, sleep efficiency was lower during daytime recovery sleep in both age-groups but the effect was more prominent in the middle-aged than in the young subjects. In both age groups, SW density, amplitude, and slope increased whereas SW positive and negative phase duration decreased during daytime recovery sleep compared to baseline sleep, particularly in anterior brain areas. Importantly, compared to young subjects, middle-aged participants showed lower SW density rebound and SW positive phase duration enhancement after sleep deprivation during daytime recovery sleep. Furthermore, middle-aged subjects showed lower SW amplitude and slope enhancements after sleep deprivation than young subjects in frontal and prefrontal derivations only. None of the SW characteristics at baseline were associated with daytime recovery sleep efficiency. Our results support the notion that anterior brain areas elicit and may necessitate more intense recovery and that aging reduces enhancement of cortical synchronization after sleep loss, particularly in these areas. Age-related changes in the quality of wake experience may underlie age-related reduction in markers of cortical synchronization enhancement after sustained wakefulness.
Slow waves constitute the main signature of sleep in the electroencephalogram (EEG). They reflect alternating periods of neuronal hyperpolarization and depolarization in cortical networks. While recent findings have demonstrated their functional role in shaping and strengthening neuronal networks, a large-scale characterization of these two processes remains elusive in the human brain. In this study, by using simultaneous scalp EEG and intracranial recordings in 10 epileptic subjects, we examined the dynamics of hyperpolarization and depolarization waves over a large extent of the human cortex. We report that both hyperpolarization and depolarization processes can occur with two different characteristic time durations which are consistent across all subjects. For both hyperpolarization and depolarization waves, their average speed over the cortex was estimated to be approximately 1 m/s. Finally, we characterized their propagation pathways by studying the preferential trajectories between most involved intracranial contacts. For both waves, although single events could begin in almost all investigated sites across the entire cortex, we found that the majority of the preferential starting locations were located in frontal regions of the brain while they had a tendency to end in posterior and temporal regions.
The human electroencephalogram (EEG) during non-rapid eye movement sleep (NREM) is characterized mainly by high-amplitude (>75 μV), slow-frequency (<4 Hz) waves (slow waves), and sleep spindles (∼11–15 Hz; >0.25 s). These NREM oscillations play a crucial role in brain plasticity, and importantly, NREM sleep oscillations change considerably with aging. This review discusses the association between NREM sleep oscillations and cerebral plasticity as well as the functional impact of age-related changes on NREM sleep oscillations. We propose that age-related reduction in sleep-dependent memory consolidation may be due in part to changes in NREM sleep oscillations.
aging; sleep; NREM; declarative memory; procedural memory; cognition; slow waves; sleep spindles
Throughout life, thalamocortical (TC) network alternates between activated states (wake or rapid eye movement sleep) and slow oscillatory state dominating slow-wave sleep. The patterns of neuronal firing are different during these distinct states. I propose that due to relatively regular firing, the activated states preset some steady state synaptic plasticity and that the silent periods of slow-wave sleep contribute to a release from this steady state synaptic plasticity. In this respect, I discuss how states of vigilance affect short-, mid-, and long-term synaptic plasticity, intrinsic neuronal plasticity, as well as homeostatic plasticity. Finally, I suggest that slow oscillation is intrinsic property of cortical network and brain homeostatic mechanisms are tuned to use all forms of plasticity to bring cortical network to the state of slow oscillation. However, prolonged and profound shift from this homeostatic balance could lead to development of paroxysmal hyperexcitability and seizures as in the case of brain trauma.
sleep; wake; oscillations; synaptic transmission; synaptic plasticity; intrinsic plasticity
When the brain is awake, neurons in the cerebral cortex fire irregularly and the electroencephalogram (EEG) displays low amplitude, high frequency fluctuations. After falling asleep, neurons start oscillating between ON periods, when they fire as during wake, and OFF periods, when they stop firing altogether, and the EEG displays high amplitude slow waves. But what happens to neuronal firing after a long period of wake? We show here in freely behaving rats that, after prolonged wake, cortical neurons can go briefly “OFF line” as they do in sleep, accompanied by slower waves in the local EEG. Strikingly, neurons often go OFF line in one cortical area and not in another. During these periods of “local sleep”, whose incidence increases with wake duration, rats appear awake, active, and display a wake EEG. However, they are progressively impaired in a sugar pellet reaching task. Thus, though both the EEG and behavior indicate wakefulness, local populations of neurons in the cortex may be falling asleep, with negative consequences on performance.
slow wave sleep; slow oscillations; EEG; cerebral cortex; multi-unit recording; reaching task; sleep deprivation
The neuronal cortical network generates slow (<1 Hz) spontaneous rhythmic activity that emerges from the recurrent connectivity. This activity occurs during slow wave sleep or anesthesia and also in cortical slices, consisting of alternating up (active, depolarized) and down (silent, hyperpolarized) states. The search for the underlying mechanisms and the possibility of analyzing network dynamics in vitro has been subject of numerous studies. This exposes the need for a detailed quantitative analysis of the membrane fluctuating behavior and computerized tools to automatically characterize the occurrence of up and down states.
Intracellular recordings from different areas of the cerebral cortex were obtained from both in vitro and in vivo preparations during slow oscillations. A method that separates up and down states recorded intracellularly is defined and analyzed here. The method exploits the crossover of moving averages, such that transitions between up and down membrane regimes can be anticipated based on recent and past voltage dynamics. We demonstrate experimentally the utility and performance of this method both offline and online, the online use allowing to trigger stimulation or other events in the desired period of the rhythm. This technique is compared with a histogram-based approach that separates the states by establishing one or two discriminating membrane potential levels. The robustness of the method presented here is tested on data that departs from highly regular alternating up and down states.
We define a simple method to detect cortical states that can be applied in real time for offline processing of large amounts of recorded data on conventional computers. Also, the online detection of up and down states will facilitate the study of cortical dynamics. An open-source MATLAB® toolbox, and Spike 2®-compatible version are made freely available.
During non-rapid eye movement (NREM) sleep and certain types of anaesthesia, neurons in the neocortex and thalamus exhibit a distinctive slow (<1 Hz) oscillation that consists of alternating UP and DOWN membrane potential states and which correlates with a pronounced slow (<1 Hz) rhythm in the EEG. Whilst several studies have claimed that the slow oscillation is generated exclusively in neocortical networks and then transmitted to other brain areas, substantial evidence exists to suggest that the full expression of the slow oscillation in an intact thalamocortical network requires the balanced interaction of oscillator systems in both the neocortex and thalamus. Within such a scenario, we have previously argued that the powerful low-threshold Ca2+ potential (LTCP)-mediated burst of action potentials that initiates the UP states in individual thalamocortical neurons may be a vital signal for instigating UP states in related cortical areas. To investigate these issues we constructed a computational model of the thalamocortical network which encompasses the important known aspects of the slow oscillation that have been garnered from earlier in vivo and in vitro experiments. By using this model we confirm that the overall expression of the slow oscillation is intricately reliant on intact connections between thalamus and cortex. In particular, we demonstrate that UP state-related LTCP-mediated bursts in thalamocortical neurons are proficient in triggering synchronous UP states in cortical networks, thereby bringing about a synchronous slow oscillation in the whole network. The importance of LTCP-mediated action potential bursts in the slow oscillation is also underlined by the observation that their associated dendritic Ca2+ signals are the only ones that inform corticothalamic synapses of the thalamocortical neuron output, since they, but not those elicited by tonic action potential firing, reach the distal dendritic sites where these synapses are located.
thalamic neurons; cortical neurons; probabilistic network model; dendrites; intrinsic calcium signalling
Cortico-thalamo-cortical circuits mediate sensation and generate neural network oscillations associated with slow-wave sleep and various epilepsies. Cortical input to sensory thalamus is thought to mainly evoke feed-forward synaptic inhibition of thalamocortical (TC) cells via reticular thalamic nucleus (nRT) neurons, especially during oscillations. This relies on a stronger synaptic strength in the cortico-nRT pathway than in the cortico-TC pathway, allowing the feed-forward inhibition of TC cells to overcome direct cortico-TC excitation. We found a systemic and specific reduction in strength in GluA4-deficient (Gria4–/–) mice of one excitatory synapse of the rhythmogenic cortico-thalamo-cortical system, the cortico-nRT projection, and observed that the oscillations could still be initiated by cortical inputs via the cortico-TC-nRT-TC pathway. These results reveal a previously unknown mode of cortico-thalamo-cortical transmission, bypassing direct cortico-nRT excitation, and describe a mechanism for pathological oscillation generation. This mode could be active under other circumstances, representing a previously unknown channel of cortico-thalamo-cortical information processing.
Cerebral cortical slow-wave activity (SWA) is prominent during sleep and also during ketamine-induced anesthesia. SWA in EEG recordings is closely linked to prominent fluctuations between up- and down-states in the membrane potential of pyramidal neurons. However, little is known about how the cerebellum is linked into SWA and whether slow oscillations influence sensory cerebellar responses. To examine these issues, we simultaneously recorded EEG from the cerebral cortex (SI, MI, and SMA), local field potentials at the input stage of cerebellar processing in the cerebellar granule cell layer (GCL) and inferior olive (IO), and single unit activity at the output stage of the cerebellum in the deep cerebellar nuclei (DCN). We found that in ketamine-anesthetized rats, SWA was synchronized between all recorded cortical areas and was phase locked with local field potentials of the GCL, IO, and single unit activity in the DCN. We found that cortical up-states are linked to activation of GCL neurons but to inhibition of cerebellar output from the DCN, with the latter an effect likely mediated by Purkinje cells. A partial coherence analysis showed further that a large portion of SWA shared between GCL and DCN was transmitted from the cortex, since the coherence shared between GCL and DCN was diminished when the effect of cortical activity was subtracted. To determine the causal flow of information between structures, a directed transfer function was calculated between the simultaneous activities of SI, MI, SMA, GCL and DCN. This analysis showed that the primary direction of information flow was from cortex to the cerebellum, and that SI had a stronger influence than other cortical areas on DCN activity. The strong functional connectivity with SI in particular is in agreement with previous findings of a strong cortical component in cerebellar sensory responses.
Rat; Deep Cerebellar Nuclei; Cerebral Cortex; Single Unit Activity; Local Field Potential; Directed Transfer Function
T-type Ca2+ channels play a number of different and pivotal roles in almost every type of neuronal oscillation expressed by thalamic neurones during non-Rapid Eye Movement (NREM) sleep, including those underlying sleep theta waves, the K-complex and the slow (<1 Hz) sleep rhythm, sleep spindles and delta waves. In particular, the transient opening of T channels not only gives rise to the ‘classical’ low threshold Ca2+ potentials, and associated high frequency burst of action potentials, that are characteristically present during sleep spindles and delta waves, but also contributes to the high threshold bursts that underlie the thalamic generation of sleep theta rhythms. The persistent opening of a small fraction of T channels, i.e. ITwindow, is responsible for the large amplitude and long lasting depolarization, or UP state, of the slow (<1 Hz) sleep oscillation in thalamic neurones. These cellular findings are in part matched by the wake-sleep phenotype of global and thalamic-selective CaV3.1 knockout mice that show a decreased amount of total NREM sleep time.
T-type Ca2+ channels, therefore, constitute the single most crucial voltage-dependent conductance that permeates all activities of thalamic neurones during NREM sleep. Since ITwindow and high threshold bursts are not restricted to thalamic neurones, the cellular neurophysiology of T channels should now move away from the simplistic, though historically significant, view of these channels as being responsible only for low threshold Ca2+ potentials.
cortex; thalamus; slow sleep oscillations; sleep spindles; delta waves; alpha rhythm; theta rhythm; ITwindow; Ih; ICAN
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.
The zona incerta (ZI) is at the crossroad of almost all major ascending and descending fiber tracts and targets numerous brain centers from the thalamus to the spinal cord. Effective ascending drive of ZI cells has been described, but the role of descending cortical signals in patterning ZI activity is unknown.
Cortical control over ZI function was examined during slow cortical waves (1-3 Hz), paroxysmal high-voltage spindles (HVSs), and 5-9 Hz oscillations in anesthetized rats. In all conditions, rhythmic cortical activity significantly altered the firing pattern of ZI neurons recorded extracellularly and labeled with the juxtacellular method. During slow oscillations, the majority of ZI neurons became synchronized to the depth-negative phase (“up state”) of the cortical waves to a degree comparable to thalamocortical neurons. During HVSs, ZI cells displayed highly rhythmic activity in tight synchrony with the cortical oscillations. ZI neurons responded to short epochs of cortical 5-9 Hz oscillations, with a change in the interspike interval distribution and with an increase in spectral density in the 5-9 Hz band as measured by wavelet analysis. Morphological reconstruction revealed that most ZI cells have mediolaterally extensive dendritic trees and very long dendritic segments. Cortical terminals established asymmetrical synapses on ZI cells with very long active zones.
These data suggest efficient integration of widespread cortical signals by single ZI neurons and strong cortical drive. We propose that the efferent GABAergic signal of ZI neurons patterned by the cortical activity can play a critical role in synchronizing thalamocortical and brainstem rhythms.
oscillation; GABA; sensorimotor; thalamocortical; basal ganglia; rhythm