ЖУРНАЛ ВЫСШЕЙ НЕРВНОЙ ДЕЯТЕЛЬНОСТИ, 2013, том 63, № 1, с. 105-112
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ТЕОРЕТИЧЕСКИЕ СТАТЬИ
УДК 612.821.6
Local Origin of Slow EEG Waves during Sleep
© 2013 Igor Timofeev
Centre de Recherche Université LavalRobert-Giffard (CRULRG), Université Laval, Québec, Canada,
e-mail: Igor.Timofeev@phs.ulaval.ca
Neuronal activity mediating EEG slow waves consists of synchronous alternation of intracellular active and silent states. Recent data demonstrate that each active state of a sleep slow wave originates in a particular cortical location and propagate to involve other cortical areas. Preferential sites of origin of these waves are: the frontal cortex in adult humans, the associative cortex in cats and the somatosensory cortex in mice. In the site of origin of these slow waves any neuron can initiate a particular cycle, however there are neuronal groups with high likelihood of triggering a particular cycle. In epileptic patients, these neurons are mostly located in superficial layers, but in healthy experimental animals, populations of intrinsically bursting neurons with a high probability of triggering spontaneous active states have been found in deeper cortical layers.
Keywords: sleep, wave, electrophysiology, cortex, thalamus, slow oscillation, intrinsic current, synaptic plasticity.
ЛОКАЛЬНОЕ КОРКОВОЕ ВОЗНИКНОВЕНИЕ МЕДЛЕННЫХ ВОЛН ЭЭГ ВО ВРЕМЯ СНА
© 2013 г. И. Тимофеев
Исследовательский центр Университета Лаваля им. Роберта Жиффарда, Университет Лаваля, Квебек, Канада, e-mail: Igor.Timofeev@phs.ulaval.ca Поступила в редакцию 23.04.2012 г.
Принята в печать 19.10.2012 г.
Известно, что нейронная корковая активация, вызывающая медленные волны ЭЭГ во время сна, состоит из синхронного чередования внутриклеточных процессов — активного и пассивного состояний нейронов. В обзоре представлены современные данные, показывающие, что активное возникновение каждой медленной волны во время сна начинается в определенной области коры мозга и распространяется на остальные области коры, вовлекая их в интегральную медленноволновую активность. Существуют предпочтительные зоны возникновения этих волн: лобная кора у взрослого человека, ассоциативная кора у кошек и соматосенсорная кора у мышей. В корковой области генеза медленных волн любой нейрон может начать новый цикл, однако существуют определенные триггерные группы нейронов, у которых более высокая вероятность запуска медленноволновой активности. У пациентов с эпилепсией эти нейроны расположены по большей части в поверхностных слоях коры, но у здоровых экспериментальных животных популяции триггерных нейронов, определяющие генез медленных волн, расположены в более глубоких слоях коры.
Ключевые слова: сон, волны ЭЭГ, электрофизиология, кора, таламус, медленноволновая активность, внутренние токи, синаптическая пластичность.
DOI: 10.7868/S0044467713010139
On a time scale of hundreds of milliseconds, one could detect two major states of cortical network: active and silent. Active network states are characterized by intensive synaptic activities
(both excitatory and inhibitory), activation of intrinsic neuronal currents and neuronal firing. Silent network states or periods of disfacilitation are dominated by leak current and some non-inacti-
vating intrinsic currents (i.e. K+ inward rectifying current). Active states of cortical network can be found during any state of vigilance. In normal conditions, silent network states can be recorded only during slow-wave sleep (SWS) [65, 73, 74]. The major questions of this review are: How the active states are generated when all connected (afferent) neurons are in silent state, and how the cortical silent states are generated when all cortical neurons are depolarized, fire, i.e. interact.
SLOW-WAVES AND SLEEP ANSTHESIA, AND SEIZURES
There are three major states of vigilance: wake, SWS and paradoxical or rapid eye movement (REM) sleep. During both waking state and REM sleep the EEG is activated (therefore these states are called activated states) and cortical neurons are relatively depolarized; most of them fire action potentials [44, 49, 65, 73, 74]. Since early studies it was shown that the majors part of sleep (now called SWS) is dominated by slow waves repeated with a frequency of about 1 Hz [5]. It was later shown on anesthetized animals that the depth-positive (surface-negative) waves of cortical field potential are mediated by a long-lasting hyperpolarization of cortical neurons and that depth-negative (surface-positive) waves of filed potential are mediated by depolarization and firing of cortical neurons. On gross scale a similar behavior was reported for pyramidal cells and in-terneurons.
Anesthesia is often used as a model of slow-wave sleep [11, 13, 64, 84]. Some features of neuronal behavior observed during sleep and under anesthesia are similar. For example during both these states the depth-positive waves of the EEG are characterized by neuronal hyperpolarization and silence whether depth-negative waves of the EEG are characterized by neuronal depolarization, vigorous synaptic activities and firing [18, 73]. During both states, SWS and anesthesia, the input resistance of cortical neurons is higher during silent states as compare to active states [20, 65]. However, there are also some remarkable differences. The slow-wave and spindle wave power is lower and the gamma power is higher under ket-amine-xylazine anesthesia than during sleep. With this anesthesia the duration of silent states is longer than during natural SWS. The amplitude of slow waves is area specific during sleep and it is uniformed under anesthesia [11]. Obviously, different anesthetics induce different patterns of activity that replicate (model) different patterns of
sleep. The frequency of slow oscillation is higher under ketamine-xylazine anesthesia as compared to urethane anesthesia [55]. Barbiturate anesthesia induces powerful spindle activities that represent a good model of stage 2 sleep [17, 19]. However, during sleep there are at least two types of spindles (fast and slow), which have different cortical distribution [43]. To the best of my knowledge, there are no experimental models that reproduce two types of spindles. The slow sleep spindles and spindles produced by barbiturate anesthesia have frequency 9—12 Hz. The fast sleep spindles have frequency 12—15 Hz that is faster than spindles recorded under anesthesia. Therefore, using just the criterion of frequency one may consider that barbiturate anesthesia is an excellent model of slow spindles. However, similarly to anesthesia conditions [16, 68], which were also reproduced in modeling experiments [6] the fast but not slow sleep spindles were synchronized with depolarizing components of the slow oscillation [43]. All together this indicates that the known mechanisms of spindle generation investigated in anesthetized animals [62] and thalamic slices [81] may not be identical to the mechanisms of spindles generation in human brain during sleep.
Epilepsy is a term that is used to define a set of about 40 different neurological diseases characterized by occurrence of unprovoked seizures. Because the main focus of the current review is generation of neocortical slow waves, I will focus on neocortical epilepsy. A vast majority of neocorti-cal seizures, the seizures triggered by neocortical activities, are nocturnal, namely they occur either during sleep or during transitions to or from SWS [67]. Neocortical seizures are primarily focal and often become secondarily generalized tonic-clonic seizures [23]. Electrographically, these seizures are most often composed of spike-wave/polyspike-wave (SW/PSW) electroen-cephalographic (EEG) discharges at 1.0—2.5 Hz and runs of fast spikes at 7—16 Hz. However, on some occasions neocortical seizures are characterized by SW complexes at approximately 3 Hz. Spontaneously occurring SW complexes at 1—2.5 Hz and fast runs at 7—16 Hz develop without discontinuity from slow (mainly 0.5—0.9 Hz) cortically generated oscillations [60, 77]. In ketamine-xyla-zine anesthetized cats the spontaneous seizures last on average close to 40 s and 70—80% of time they are composed of SW complexes [8]. During fast runs the membrane potential of cortical neurons oscillate with frequencies similar, but not identical to the EEG and the amplitude of these
oscillations is lower as compare to the SW complexes [8]. During SW complexes the membrane potential of cortical neurons oscillate in phase with the EEG and like during sleep slow oscillation the depth-positive EEG waves are associated with neuronal hyperpolarization and silence while depth-negative waves of EEG are associated with neuronal depolarization and firing [59, 77]. Therefore, on gross scale the activity of cortical neurons during SW complexes of seizures resembles their activity during slow oscillation of sleep. However, there are some critical differences. Silent phases of sleep slow oscillation are periods of disfacilitiation, characterized by absence of syn-aptic activity and dominated by leak current [20, 70, 73]. Active phases of slow oscillation are generated almost exclusively by a well-tuned interplay of excitatory and inhibitory conductances [30, 49, 73]. During seizures, in addition to leak-current-dependent potential the silent phases are also helped with Ca2+- activated (and likely Na+) K+ currents [67, 72]. Profound hyperpolarization and increased extracellular concentration of K+ strongly activate h-current (hyperpolarization activated depolarizing current) that leads to the generation of the next depolarizing period [69]. Due to reduced extracellular concentration of Ca2+ the synaptic activities (excitatory and inhibitory) during depolarizing phases of seizures are reduced, and Cl-dependent inhibitory potentials become depolarizing; however, persistent Na+ and high threshold Ca2+ currents strongly contribute to neuronal depolarization [66, 67, 72, 75, 77]. Altogether, it results in a much stronger d
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