Short-Duration Epileptic Discharges Show a Distinct Phase Preference During Ongoing Hippocampal Slow Oscillations

2010 ◽  
Vol 104 (4) ◽  
pp. 2194-2202 ◽  
Author(s):  
Philip H. de Guzman ◽  
Farhang Nazer ◽  
Clayton T. Dickson

Non-REM (slow-wave) sleep has been shown to facilitate temporal lobe epileptiform events, whereas REM sleep seems more restrictive. This state-dependent modulation may be the result of the enhancement of excitatory synaptic transmission and/or the degree of network synchronization expressed within the hippocampus of the temporal lobe. The slow oscillation (SO), a ∼1 Hz oscillatory pattern expressed during non-REM sleep and urethane anesthesia, has been recently shown to facilitate the generation, maintenance, and propagation of stimulus-evoked epileptiform activity in the hippocampus. To further address the state-dependent modulation of epileptic activity during the SO, we studied the properties of short-duration interictal-like activity generated by focal application of penicillin in the hippocampus of urethane-anesthetized rats. Epileptiform spikes were larger but only slightly more prevalent during the SO as opposed to the theta (REM-like) state. More notably, however, epileptic spikes had a significant tendency to occur just following the peak negativity of ongoing SO cycles. Because of the known phase-dependent changes in 1) synaptic excitability (just following the positive peak of the SO) and 2) network synchronization (during the negative peak of the SO), these results suggest that it is the synchrony and not the changes in synaptic excitability that lead to the facilitation of epileptiform activity during sleep-like slow wave states.

2020 ◽  
Author(s):  
Chun-Qing Zhang ◽  
Mackenzie A Catron ◽  
Li Ding ◽  
Caitlyn M Hanna ◽  
Martin J Gallagher ◽  
...  

Abstract Epileptic activity in genetic generalized epilepsy (GGE) patients preferentially appears during sleep and its mechanism remains unknown. Here, we found that sleep-like slow-wave oscillations (0.5 Hz SWOs) potentiated excitatory and inhibitory synaptic currents in layer V cortical pyramidal neurons from wild-type (wt) mouse brain slices. In contrast, SWOs potentiated excitatory, but not inhibitory, currents in cortical neurons from a heterozygous (het) knock-in (KI) Gabrg2+Q/390X model of Dravet epilepsy syndrome. This created an imbalance between evoked excitatory and inhibitory currents to effectively prompt neuronal action potential firings. Similarly, physiologically similar up-/down-state induction (present during slow-wave sleep) in cortical neurons also potentiated excitatory synaptic currents within brain slices from wt and het KI mice. Moreover, this state-dependent potentiation of excitatory synaptic currents entailed some signaling pathways of homeostatic synaptic plasticity. Consequently, in het KI mice, in vivo SWO induction (using optogenetic methods) triggered generalized epileptic spike-wave discharges (SWDs), being accompanied by sudden immobility, facial myoclonus, and vibrissa twitching. In contrast, in wt littermates, SWO induction did not cause epileptic SWDs and motor behaviors. To our knowledge, this is the first mechanism to explain why epileptic SWDs preferentially happen during non rapid eye-movement sleep and quiet-wakefulness in human GGE patients.


1977 ◽  
Vol 55 (2) ◽  
pp. 234-242 ◽  
Author(s):  
M. Rezek ◽  
V. Havlicek ◽  
L. Leybin ◽  
C. Pinsky ◽  
E. A. Kroeger ◽  
...  

The administration of small doses of somatostatin (SRIF) (0.01 and 0.1 μg) into the neostriatal complex of unrestrained, freely moving rats induced general behavioral excitation associated with a variety of stereotyped movements, tremors, and a reduction of rapid eye movements (REM) and deep slow wave sleep (SWS). In contrast, the higher doses of SRIF (1.0 and 10.0 μg) caused movements to be uncoordinated and frequently induced more severe difficulties in motor control such as contralateral hemiplegia-in-extension which restricted or completely prevented the expression of normal behavioral patterns. As a result, the animals appeared drowsy and inhibited. Analysis of the sleep-waking cycle revealed prolonged periods of a shallow SWS while REM sleep and deep SWS were markedly reduced; electroencephalogram recordings revealed periods of dissociation from behavior. The administration of endocrinologically inactive as well as the active analogues of SRIF failed to induce effects comparable with those observed after the administration of the same dose of the native hormone (10.0 μg).


SLEEP ◽  
2020 ◽  
Vol 43 (7) ◽  
Author(s):  
Sébastien Arthaud ◽  
Paul-Antoine Libourel ◽  
Pierre-Hervé Luppi ◽  
Christelle Peyron

Abstract Identifying the precise neuronal networks activated during paradoxical sleep (PS, also called REM sleep) has been a challenge since its discovery. Similarly, our understanding of the homeostatic mechanisms regulating PS, whether through external modulation by circadian and ultradian drives or via intrinsic homeostatic regulation, is still limited, largely due to interfering factors rendering the investigation difficult. Indeed, none of the studies published so far were able to manipulate PS without significantly altering slow-wave sleep and/or stress level, thus introducing a potential bias in the analyses. With the aim of achieving a better understanding of PS homeostasis, we developed a new method based on automated scoring of vigilance states—using electroencephalogram and electromyogram features—and which involves closed-loop PS deprivation through the induction of cage floor movements when PS is detected. Vigilance states were analyzed during 6 and 48 h of PS deprivation as well as their following recovery periods. Using this new automated methodology, we were able to deprive mice of PS with high efficiency and specificity, for short or longer periods of time, observing no sign of stress (as evaluated by plasma corticosterone level and sleep latency) and requiring no human intervention or environmental changes. We show here that PS can be homeostatically modulated and regulated while no significant changes are induced on slow-wave sleep and wakefulness, with a PS rebound duration depending on the amount of prior PS deficit. We also show that PS interval duration is not correlated with prior PS episode duration in the context of recovery from PS deprivation.


2000 ◽  
Vol 23 (6) ◽  
pp. 941-943 ◽  
Author(s):  
Claude Gottesmann

Reflective waking mentation is supported by cortical activating and inhibitory processes. The thought-like mental content of slow wave sleep appears with lower levels of both kinds of influence. During REM sleep, the equation: activation + disinhibition + dopamine may explain the often psychotic-like mode of psychological functioning.[Hobson et al.; Nielsen; Revonsuo; Solms; Vertes & Eastman]


SLEEP ◽  
2009 ◽  
Vol 32 (3) ◽  
pp. 302-310 ◽  
Author(s):  
Lisa Genzel ◽  
Martin Dresler ◽  
Renate Wehrle ◽  
Michael Grözinger ◽  
Axel Steiger

2001 ◽  
Vol 91 (5) ◽  
pp. 2289-2297 ◽  
Author(s):  
Thom R. Feroah ◽  
H. V. Forster ◽  
L. Pan ◽  
N. E. Schlick ◽  
Paul Martino ◽  
...  

Our aim was to investigate the effects of the negative pressure reflex on mechanically opposing pharyngeal muscles during wakefulness, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. In four goats with isolated upper airways, we measured tracheal airflow and electrical activity of the thyropharyngeus (TP; constricting), the stylopharyngeus (SP; dilating), and the diaphragm (Dia). In the wakefulness state in response to negative pressure tests, TP decreased (65%), SP increased (198%), and tidal volume (Vt) (66%) and rate of rise of Dia (Diaslope, 69%) decreased ( P < 0.02). Similarly, during SWS, the negative pressure response of TP (31%), Vt (61%), and Diaslope (60%) decreased, whereas SP (113%) increased, relative to SWS control ( P < 0.02). In REM sleep, the negative pressure response by TP and SP were small, whereas both Vt (38%) and Diaslope (24%) were greatly decreased ( P < 0.02) compared with REM control. Inspiratory duration remained unchanged in response to negative pressure tests in all states. These data provide evidence that mechanically opposing inspiratory and expiratory pharyngeal muscles are reciprocally controlled and their response to negative pressure are state dependent.


1999 ◽  
Vol 81 (2) ◽  
pp. 584-595 ◽  
Author(s):  
Cynthia G. Leung ◽  
Peggy Mason

Physiological properties of raphe magnus neurons during sleep and waking. Neurons in the medullary raphe magnus (RM) that are important in the descending modulation of nociceptive transmission are classified by their response to noxious tail heat as on,off, or neutral cells. Experiments in anesthetized animals demonstrate that RM on cells facilitate and off cells inhibit nociceptive transmission. Yet little is known of the physiology of these cells in the unanesthetized animal. The first aim of the present experiments was to determine whether cells with on- and off-like responses to noxious heat exist in the unanesthetized rat. Second, to determine if RM cells have state-dependent discharge, the activity of RM neurons was recorded during waking and sleeping states. Noxious heat applied during waking and slow wave sleep excited one group of cells (on-u) in unanesthetized rats. Other cells were inhibited by noxious heat (off-u) applied during waking and slow wave sleep states in unanesthetized rats. Neutral-u cells did not respond to noxious thermal stimulation applied during either slow wave sleep or waking. On-u and off-u cells were more likely to respond to noxious heat during slow wave sleep than during waking and were least likely to respond when the animal was eating or drinking. Although RM cells rarely respond to innocuous stimulation applied during anesthesia, on-u andoff-u cells were excited and inhibited, respectively, by innocuous somatosensory stimulation in the unanesthetized rat. The spontaneous activity of >90% of the RM neurons recorded in the unanesthetized rat was influenced by behavioral state. Off-u cells discharged sporadically during waking but were continuously active during slow wave sleep. By contrast,on-u and neutral-u cells discharged in bursts during waking and either ceased to discharge entirely or discharged at a low rate during slow wave sleep. We suggest that off cell discharge functions to suppress pain-evoked reactions during sleep, whereas on cell discharge facilitates pain-evoked responses during waking.


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