scholarly journals Sleep slow-wave oscillations trigger seizures in a genetic epilepsy model of Dravet syndrome

2022 ◽  
Author(s):  
Mackenzie A. Catron ◽  
Rachel K. Howe ◽  
Gai-Linn K. Besing ◽  
Emily K. St. John ◽  
Cobie Victoria Potesta ◽  
...  
Keyword(s):  
Slow Wave ◽  
Epileptic Seizures ◽  
Nrem Sleep ◽  
Dravet Syndrome ◽  
Brain State ◽  
Synaptic Potentiation ◽  
Sleep Period ◽  
State Dependent ◽  
Slow Wave Oscillations

Sleep is the brain state when cortical activity decreases and memory consolidates. However, in human epileptic patients, including genetic epileptic seizures such as Dravet syndrome, sleep is the preferential period when epileptic spike-wave discharges (SWDs) appear, with more severe epileptic symptoms in female patients than male patients, which influencing patient sleep quality and memory. Currently, seizure onset mechanisms during sleep period still remain unknown. Our previous work has shown that the sleep-like state-dependent synaptic potentiation mechanism can trigger epileptic SWDs (Zhang et al., 2021). In this study, using one heterozygous (het) knock-in (KI) transgenic mice (GABAA receptor γ2 subunit Gabrg2Q390X mutation) and an optogenetic method, we hypothesized that slow-wave oscillations (SWOs) themselves in vivo could trigger epileptic seizures. We found that epileptic SWDs in het Gabrg2+/Q390X KI mice exhibited preferential incidence during NREM sleep period, accompanied by motor immobility/ facial myoclonus/vibrissal twitching, with more frequent incidence in female het KI mice than male het KI mice. Optogenetic induced SWOs in vivo significantly increased epileptic seizure incidence in het Gabrg2+/Q390X KI mice with increased duration of NREM sleep or quiet-wakeful states. Furthermore, suppression of SWO-related homeostatic synaptic potentiation by 4-(diethylamino)-benzaldehyde (DEAB) injection (i.p.) greatly decreased seizure incidence in het KI mice, suggesting that SWOs did trigger seizure activity in het KI mice. In addition, EEG delta-frequency (0.1-4 Hz) power spectral density during NREM sleep was significantly larger in female het Gabrg2+/Q390X KI mice than male het Gabrg2+/Q390X KI mice, which likely contributes to the gender difference in seizure incidence during NREM sleep/quiet-wake as that in human patients.

Myogenic mechanism for peristalsis in the cat esophagus

1999 ◽  
Vol 277 (2) ◽  
pp. G306-G313 ◽  
Author(s):  
Harold G. Preiksaitis ◽  
Nicholas E. Diamant
Keyword(s):  
Muscle Contraction ◽  
Slow Wave ◽  
Circular Muscle ◽  
Smooth Muscle Contraction ◽  
Slow Waves ◽  
Mechanical Activity ◽  
Control Mechanisms ◽  
Slow Wave Oscillations

A myogenic control system (MCS) is a fundamental determinant of peristalsis in the stomach, small bowel, and colon. In the esophagus, attention has focused on neuronal control, the potential for a MCS receiving less attention. The myogenic properties of the cat esophagus were studied in vitro with and without nerves blocked by 1 μM TTX. Muscle contraction was recorded, while electrical activity was monitored by suction electrodes. Spontaneous, nonperistaltic, electrical, and mechanical activity was seen in the longitudinal muscle and persisted after TTX. Spontaneous circular muscle activity was minimal, and peristalsis was not observed without pharmacological activation. Direct electrical stimulation (ES) in the presence of bethanechol or tetraethylammonium chloride (TEA) produced slow-wave oscillations and spike potentials accompanying smooth muscle contraction that progressed along the esophagus. Increased concentrations of either drug in the presence of TTX produced slow waves and spike discharges, accompanied by peristalsis in 5 of 8 TEA- and 2 of 11 bethanechol-stimulated preparations without ES. Depolarization of the muscle by increasing K+ concentration also produced slow waves but no peristalsis. We conclude that the MCS in the esophagus requires specific activation and is manifest by slow-wave oscillations of the membrane potential, which appear to be necessary, but are not sufficient for myogenic peristalsis. In vivo, additional control mechanisms are likely supplied by nerves.

scholarly journals 0074 Inhibitory Neurons in the Dorsomedial Medulla Promote REM Sleep

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A30-A30
Author(s):  
J Stucynski ◽  
A Schott ◽  
J Baik ◽  
J Hong ◽  
F Weber ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Nrem Sleep ◽  
Inhibitory Neurons ◽  
Brain State ◽  
Sleep Regulation ◽  
Optogenetic Stimulation ◽  
Electrophysiological Recordings ◽  
Stimulation Of

Abstract Introduction The neural circuits controlling rapid eye movement (REM) sleep, and in particular the role of the medulla in regulating this brain state, remains an active area of study. Previous electrophysiological recordings in the dorsomedial medulla (DM) and electrical stimulation experiments suggested an important role of this area in the control of REM sleep. However the identity of the involved neurons and their precise role in REM sleep regulation are still unclear. Methods The properties of DM GAD2 neurons in mice were investigated through stereotaxic injection of CRE-dependent viruses in conjunction with implantation of electrodes for electroencephalogram (EEG) and electromyogram (EMG) recordings and optic fibers. Experiments included in vivo calcium imaging (fiber photometry) across sleep and wake states, optogenetic stimulation of cell bodies, chemogenetic excitation and suppression (DREADDs), and connectivity mapping using viral tracing and optogenetics. Results Imaging the calcium activity of DM GAD2 neurons in vivo indicates that these neurons are most active during REM sleep. Optogenetic stimulation of DM GAD2 neurons reliably triggered transitions into REM sleep from NREM sleep. Consistent with this, chemogenetic activation of DM GAD2 neurons increased the amount of REM sleep while inhibition suppressed its occurrence and enhanced NREM sleep. Anatomical tracing revealed that DM GAD2 neurons project to several areas involved in sleep / wake regulation including the wake-promoting locus coeruleus (LC) and the REM sleep-suppressing ventrolateral periaquaductal gray (vlPAG). Optogenetic activation of axonal projections from DM to LC, and DM to vlPAG was sufficient to induce REM sleep. Conclusion These experiments demonstrate that DM inhibitory neurons expressing GAD2 powerfully promote initiation of REM sleep in mice. These findings further characterize the dorsomedial medulla as a critical structure involved in REM sleep regulation and inform future investigations of the REM sleep circuitry. Support R01 HL149133

scholarly journals All-optical electrophysiology reveals brain-state dependent changes in hippocampal subthreshold dynamics and excitability

2018 ◽  
Author(s):  
Yoav Adam ◽  
Jeong J. Kim ◽  
Shan Lou ◽  
Yongxin Zhao ◽  
Daan Brinks ◽  
...  
Keyword(s):  
High Speed ◽  
Near Infrared ◽  
Neuronal Excitability ◽  
Signal To Noise Ratio ◽  
Brain State ◽  
Promising Tool ◽  
State Dependent ◽  
Subthreshold Voltage ◽  
Targeted Gene Expression

AbstractA technology to record membrane potential from multiple neurons, simultaneously, in behaving animals will have a transformative impact on neuroscience research1. Parallel recordings could reveal the subthreshold potentials and intercellular correlations that underlie network behavior2. Paired stimulation and recording can further reveal the input-output properties of individual cells or networks in the context of different brain states3. Genetically encoded voltage indicators are a promising tool for these purposes, but were so far limited to single-cell recordings with marginal signal to noise ratio (SNR) in vivo4-6. We developed improved near infrared voltage indicators, high speed microscopes and targeted gene expression schemes which enabled recordings of supra- and subthreshold voltage dynamics from multiple neurons simultaneously in mouse hippocampus, in vivo. The reporters revealed sub-cellular details of back-propagating action potentials, correlations in sub-threshold voltage between multiple cells, and changes in dynamics associated with transitions from resting to locomotion. In combination with optogenetic stimulation, the reporters revealed brain state-dependent changes in neuronal excitability, reflecting the interplay of excitatory and inhibitory synaptic inputs. These tools open the possibility for detailed explorations of network dynamics in the context of behavior.

scholarly journals In Vivo Optogenetic Stimulation of Neocortical Excitatory Neurons Drives Brain-State-Dependent Inhibition

2011 ◽  
Vol 21 (19) ◽  
pp. 1593-1602 ◽  
Author(s):  
Celine Mateo ◽  
Michael Avermann ◽  
Luc J. Gentet ◽  
Feng Zhang ◽  
Karl Deisseroth ◽  
...  
Keyword(s):  
Brain State ◽  
Optogenetic Stimulation ◽  
State Dependent ◽  
Excitatory Neurons ◽  
Dependent Inhibition ◽  
Stimulation Of

scholarly journals Impaired State-Dependent Potentiation of GABAergic Synaptic Currents Triggers Seizures in a Genetic Generalized Epilepsy Model

2020 ◽  
Author(s):  
Chun-Qing Zhang ◽  
Mackenzie A Catron ◽  
Li Ding ◽  
Caitlyn M Hanna ◽  
Martin J Gallagher ◽  
...  
Keyword(s):  
Slow Wave ◽  
Cortical Neurons ◽  
Slow Wave Sleep ◽  
Brain Slices ◽  
Epileptic Activity ◽  
Epilepsy Syndrome ◽  
Synaptic Currents ◽  
State Dependent ◽  
Generalized Epilepsy

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.

scholarly journals A Rodent Model of Night-Shift Work Induces Short-Term and Enduring Sleep and Electroencephalographic Disturbances

2016 ◽  
Vol 32 (1) ◽  
pp. 48-63 ◽  
Author(s):  
Janne Grønli ◽  
Peter Meerlo ◽  
Torhild T. Pedersen ◽  
Ståle Pallesen ◽  
Silje Skrede ◽  
...  
Keyword(s):  
Shift Work ◽  
Slow Wave ◽  
Night Shift ◽  
Active Phase ◽  
Nrem Sleep ◽  
Night Work ◽  
Brain State ◽  
Work Schedule ◽  
Night Shift Work ◽  
Increased Risk

Millions of people worldwide are working at times that overlap with the normal time for sleep. Sleep problems related to the work schedule may mediate the well-established relationship between shift work and increased risk for disease, occupational errors and accidents. Yet, our understanding of causality and the underlying mechanisms that explain this relationship is limited. We aimed to assess the consequences of night-shift work for sleep and to examine whether night-shift work-induced sleep disturbances may yield electrophysiological markers of impaired maintenance of the waking brain state. An experimental model developed in rats simulated a 4-day protocol of night-work in humans. Two groups of rats underwent 8-h sessions of enforced ambulation, either at the circadian time when the animal was physiologically primed for wakefulness (active-workers, mimicking day-shift) or for sleep (rest-workers, mimicking night-shift). The 4-day rest-work schedule induced a pronounced redistribution of sleep to the endogenous active phase. Rest-work also led to higher electroencephalogram (EEG) slow-wave (1-4 Hz) energy in quiet wakefulness during work-sessions, suggesting a degraded waking state. After the daily work-sessions, being in their endogenous active phase, rest-workers slept less and had higher gamma (80-90 Hz) activity during wake than active-workers. Finally, rest-work induced an enduring shift in the main sleep period and attenuated the accumulation of slow-wave energy during NREM sleep. A comparison of recovery data from 12:12 LD and constant dark conditions suggests that reduced time in NREM sleep throughout the recorded 7-day recovery phase induced by rest-work may be modulated by circadian factors. Our data in rats show that enforced night-work-like activity during the normal resting phase has pronounced acute and persistent effects on sleep and waking behavior. The study also underscores the potential importance of animal models for future studies on the health consequences of night-shift work and the mechanisms underlying increased risk for diseases.

scholarly journals Populations of striatal medium spiny neurons encode vibrotactile frequency in rats: modulation by slow wave oscillations

2013 ◽  
Vol 109 (2) ◽  
pp. 315-320 ◽  
Author(s):  
Thomas G. Hawking ◽  
Todor V. Gerdjikov
Keyword(s):  
Slow Wave ◽  
Stimulus Frequency ◽  
Medium Spiny Neuron ◽  
Brain State ◽  
Projection Neurons ◽  
Medium Spiny Neurons ◽  
Population Responses ◽  
Spiny Neurons ◽  
Striatal Projection Neurons ◽  
Slow Wave Oscillations

Dorsolateral striatum (DLS) is implicated in tactile perception and receives strong projections from somatosensory cortex. However, the sensory representations encoded by striatal projection neurons are not well understood. Here we characterized the contribution of DLS to the encoding of vibrotactile information in rats by assessing striatal responses to precise frequency stimuli delivered to a single vibrissa. We applied stimuli in a frequency range (45–90 Hz) that evokes discriminable percepts and carries most of the power of vibrissa vibration elicited by a range of complex fine textures. Both medium spiny neurons and evoked potentials showed tactile responses that were modulated by slow wave oscillations. Furthermore, medium spiny neuron population responses represented stimulus frequency on par with previously reported behavioral benchmarks. Our results suggest that striatum encodes frequency information of vibrotactile stimuli which is dynamically modulated by ongoing brain state.

scholarly journals Sex differences in slow-wave electroencephalographic activity (SWA) in adolescent depression

2012 ◽  
Vol 4 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Jorge Lopez ◽  
Robert Hoffmann ◽  
Graham Emslie ◽  
Roseanne Armitage
Keyword(s):  
Sex Differences ◽  
Slow Wave ◽  
Sleep Disturbances ◽  
Adolescent Depression ◽  
Nrem Sleep ◽  
Healthy Controls ◽  
Adult Males ◽  
Major Depressive ◽  
Sleep Period ◽  
Electroencephalographic Activity

Sleep disturbances, present in more than 90% of major depressive disorder (MDD) patients, are moderated by sex in adult MDD. In particular, slow-wave electroencephalographic activity (SWA; 0.5-4 Hz) accumulation is low and dissipation impaired. This SWA abnormality in depressed adult males does not change with age, suggesting that SWA abnormality appears at early ages. The present study evaluated sex differences in SWA in adolescents with MDD compared to healthy controls. We evaluated regularized sleep-wake schedules at home for 5-7 days, followed by two consecutive nights of sleep EEG recording. The study included 104 participants, 52 symptomatic and depressed subjects (MDD: 20 males and 32 females) and 52 healthy controls (HC: 20 males and 32 females), aged 13-18 years. SWA power and dissipation, and duration and latencies to each Non-Rapid Eye Movement (NREM) sleep period were calculated for each group. Results showed that SWA accumulation in the first NREM period was lower and its dissipation across the night more irregular in MDD males compared to HC males (P<0.009). By contrast, SWA was equivalent in MDD and HC females. In conclusion, as reported in adult MDD, the accumulation and dissipation of SWA was abnormal in depressed adolescents, but only in males. SWA abnormalities in adolescent MDD may relate to different depressive symptoms in females and males. These results underscore the need to develop sex-specific therapies to enhance and restore SWA in depressed adolescents.

Hippocampus: Intrinsic Organization

2017 ◽  
pp. 199-216
Author(s):  
Peter Somogyi ◽  
Thomas Klausberger
Keyword(s):  
Cerebral Cortex ◽  
Granule Cells ◽  
Pyramidal Cells ◽  
Spike Timing ◽  
Gabaergic Neurons ◽  
Brain State ◽  
Firing Rates ◽  
State Dependent ◽  
Postsynaptic Cell

The hippocampus, together with the subiculum, represent an associational area of the cerebral cortex that is intimately involved in mnemonic processes. Through its connections with other areas of the temporal lobe, the prefrontal cortex (PFC) and subcortical areas, it contributes to the encoding, association, consolidation, and recall of representations of the external and internal world in the combined firing rates and spike timing of glutamatergic pyramidal and granule cells. Pyramidal cell assemblies are formed and segregated from other assemblies by the dynamic strengthening and weakening of glutamatergic synaptic weights both on pyramidal cells and GABAergic interneurons. Interneurons, generate postsynaptic cell domain and brain state–dependent rhythmic changes in excitability, which are key for the formation, consolidation, and recall of representations. The chapter attempts to allocate explicit roles for some GABAergic neurons, based on their firing patterns in vivo as observed in identified neurons.

scholarly journals Differential cell-type dependent brain state modulations of sensory representations in the non-lemniscal mouse inferior colliculus

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Chenggang Chen ◽  
Sen Song
Keyword(s):  
Inferior Colliculus ◽  
Calcium Imaging ◽  
Inhibitory Neurons ◽  
Brain State ◽  
Spectral Tuning ◽  
State Dependent ◽  
Excitatory Neurons ◽  
Sensory Responses ◽  
Highly Correlated

Abstract Sensory responses of the neocortex are strongly influenced by brain state changes. However, it remains unclear whether and how the sensory responses of the midbrain are affected. Here we addressed this issue by using in vivo two-photon calcium imaging to monitor the spontaneous and sound-evoked activities in the mouse inferior colliculus (IC). We developed a method enabling us to image the first layer of non-lemniscal IC (IC shell L1) in awake behaving mice. Compared with the awake state, spectral tuning selectivity of excitatory neurons was decreased during isoflurane anesthesia. Calcium imaging in behaving animals revealed that activities of inhibitory neurons were highly correlated with locomotion. Compared with stationary periods, spectral tuning selectivity of excitatory neurons was increased during locomotion. Taken together, our studies reveal that neuronal activities in the IC shell L1 are brain state dependent, whereas the brain state modulates the excitatory and inhibitory neurons differentially.

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