scholarly journals Role of somatostatin-positive cortical interneurons in the generation of sleep slow waves

2017 ◽  
Author(s):  
Chadd M. Funk ◽  
Kayla Peelman ◽  
Michele Bellesi ◽  
William Marshall ◽  
Chiara Cirelli ◽  
...  
Keyword(s):  
Slow Wave ◽  
Cortical Neurons ◽  
Nrem Sleep ◽  
Slow Waves ◽  
Inhibitory Neurons ◽  
Excitatory Transmission ◽  
Cortical Interneurons ◽  
Somatic Inhibition ◽  
Apical Dendrites

SUMMARYCortical slow waves – the hallmark of NREM sleep - reflect near-synchronous OFF periods in cortical neurons. However, the mechanisms triggering such OFF periods are unclear, as there is little evidence for somatic inhibition. We studied cortical inhibitory interneurons that express somatostatin (SOM), because ∼70% of them are Martinotti cells that target diffusely layer 1 and can block excitatory transmission presynaptically, at glutamatergic terminals, and postsynaptically, at apical dendrites, without inhibiting the soma. In freely moving mice, we show that SOM+ cells can fire immediately before slow waves and their optogenetic stimulation triggers neuronal OFF periods during sleep. Next, we show that chemogenetic activation of SOM+ cells increases slow wave activity (SWA), the slope of individual slow waves, and the duration of NREM sleep; whereas their chemogenetic inhibition decreases SWA and slow wave incidence without changing time spent asleep. By contrast, activation of parvalbumin+ (PV+) cells, the most numerous population of cortical inhibitory neurons, greatly decreases SWA and cortical firing. These results indicate that SOM+ cells, but not PV+ cells, are involved in the generation of sleep slow waves. Whether Martinotti cells are solely responsible for this effect, or are complemented by other classes of inhibitory neurons, remains to be investigated.

scholarly journals KCC2 overexpression prevents the paradoxical seizure-promoting action of somatic inhibition

2018 ◽  
Author(s):  
Vincent Magloire ◽  
Jonathan Cornford ◽  
Andreas Lieb ◽  
Dimitri M. Kullmann ◽  
Ivan Pavlov
Keyword(s):  
Potassium Chloride ◽  
Cortical Neurons ◽  
Closed Loop ◽  
Network Activity ◽  
Intracellular Chloride ◽  
Cortical Interneurons ◽  
The Face ◽  
Somatic Inhibition

AbstractAlthough cortical interneurons are apparently well-placed to suppress seizures, several recent reports have highlighted a paradoxical role of parvalbumin-positive perisomatic-targeting (PV+) interneurons in ictogenesis. Here, we use an acute in vivo model of focal cortical seizures in awake behaving mice, together with closed-loop optogenetic manipulation of PV+ interneurons, to investigate their function during seizures. We show that photo-depolarization of PV+ interneurons rapidly switches from an anti-ictal to a pro-ictal effect within a few seconds of seizure initiation. The pro-ictal effect of delayed photostimulation of PV+ interneurons was not shared with dendrite-targeting somatostatin-positive (SOM+) interneurons. We also show that this switch can be prevented by overexpression of the neuronal potassium-chloride co-transporter KCC2 in principal cortical neurons. These results suggest that strategies aimed at improving the ability of principal neurons to maintain intracellular chloride levels in the face of excessive network activity can prevent interneurons from contributing to seizure perpetuation.

scholarly journals Role of Somatostatin-Positive Cortical Interneurons in the Generation of Sleep Slow Waves

2017 ◽  
Vol 37 (38) ◽  
pp. 9132-9148 ◽  
Author(s):  
Chadd M. Funk ◽  
Kayla Peelman ◽  
Michele Bellesi ◽  
William Marshall ◽  
Chiara Cirelli ◽  
...  
Keyword(s):  
Slow Waves ◽  
Cortical Interneurons

scholarly journals Bidirectional Interaction of Hippocampal Ripples and Cortical Slow Waves Leads to Coordinated Spiking Activity During NREM Sleep

2020 ◽  
Vol 31 (1) ◽  
pp. 324-340
Author(s):  
Pavel Sanda ◽  
Paola Malerba ◽  
Xi Jiang ◽  
Giri P Krishnan ◽  
Jorge Gonzalez-Martinez ◽  
...  
Keyword(s):  
Slow Wave ◽  
Memory Consolidation ◽  
Slow Wave Sleep ◽  
Nrem Sleep ◽  
Slow Waves ◽  
Slow Oscillation ◽  
Cortical Input ◽  
Sharp Wave ◽  
Up States ◽  
Intracranial Recordings

Abstract The dialogue between cortex and hippocampus is known to be crucial for sleep-dependent memory consolidation. During slow wave sleep, memory replay depends on slow oscillation (SO) and spindles in the (neo)cortex and sharp wave-ripples (SWRs) in the hippocampus. The mechanisms underlying interaction of these rhythms are poorly understood. We examined the interaction between cortical SO and hippocampal SWRs in a model of the hippocampo–cortico–thalamic network and compared the results with human intracranial recordings during sleep. We observed that ripple occurrence peaked following the onset of an Up-state of SO and that cortical input to hippocampus was crucial to maintain this relationship. A small fraction of ripples occurred during the Down-state and controlled initiation of the next Up-state. We observed that the effect of ripple depends on its precise timing, which supports the idea that ripples occurring at different phases of SO might serve different functions, particularly in the context of encoding the new and reactivation of the old memories during memory consolidation. The study revealed complex bidirectional interaction of SWRs and SO in which early hippocampal ripples influence transitions to Up-state, while cortical Up-states control occurrence of the later ripples, which in turn influence transition to Down-state.

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 1133 The Recovery of Sleep Oscillations in Acute to Chronic Traumatic Brain Injury

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A431-A431
Author(s):  
E Sanchez ◽  
C Duclos ◽  
S Van Der Maren ◽  
H El-Khatib ◽  
C Arbour ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Slow Wave ◽  
Nrem Sleep ◽  
Slow Waves ◽  
Hospital Environment ◽  
Chronic Stage ◽  
Orthopedic Injuries ◽  
The Brain ◽  
Sleep Cycles

Abstract Introduction Slow waves and spindles are essential oscillations occurring during NREM sleep that may be disrupted by moderate to severe traumatic brain injury (TBI). We investigated these oscillations in the acute and chronic trauma stage. Methods Four groups were tested with whole-night polysomnography: hospitalized patients with acute TBI (n=10, 29.7±13.8y) or severe orthopedic injuries (n=15, 39.9±17.1y), chronic TBI including 9 returning from the acute TBI group (n=43, 31.9±13.5y), and healthy controls (n=36, 30.5±12.7y). Characteristics for slow waves (density, amplitude, slope, frequency, duration) and spindles (density, amplitude, frequency, duration) were quantified over N2 and N3 sleep for the first three sleep cycles, and groups were compared using one-way ANOVAs. Results One-way ANOVAs showed group effects only for slow wave density (F=4.11 to 6.04, p=0.009 to 0.0008)) and spindle density (F=3.3 to 8.8, p=0.02 to 0.00003). These effects were present for the 2nd and 3rd sleep cycles, but not the 1st. More specifically, slow wave density in acute TBI was higher than in controls, and returned to normal levels in the chronic stage. Conversely, spindle density in acute TBI was lower than in controls and returned to normal levels in the chronic stage. No group difference was observed for the orthopedic group. Conclusion Our results suggest that immediately after a severely disruptive event such as a TBI, the brain needs additional deeper sleep to recover, resulting in more slow waves but also in less spindles. These changes are only present in the 2nd and 3rd sleep cycles, reflecting an absence of the expected dissipation of slow waves, which may suggest increased homeostatic sleep pressure due to the brain injury. Limits to interpretation include the hospital environment and medication, but the absence of changes in the orthopedic group under similar conditions emphasizes the effect of the brain injury itself. Support Canadian Institutes of Health Research (CIHR) and Fonds de Recherche Québec-Santé (FRQS)

scholarly journals Modulation of nociception by corticotrigeminal pathway- A narrative review

Mediscope ◽  
2020 ◽  
Vol 7 (1) ◽  
pp. 51-57
Author(s):  
Sayema Ainan
Keyword(s):  
Nervous System ◽  
Trigeminal Nerve ◽  
Cortical Neurons ◽  
Pain Perception ◽  
Pain Treatment ◽  
Early Stage ◽  
Short Review ◽  
Inhibitory Neurons ◽  
Pain Sensation

Management of chronic pain is one of the most important reason to which medications are given. Traditional medicines which have been used to relieve pain are having a number of limitations. Therefore, novel therapies for pain treatment are essential. Our nervous system can process any kind of injurious stimuli, which is known as nociception. The mechanism of nociception involves a complex interaction of peripheral and central nervous system structures. Brain or cerebral cortex has its own controlling mechanism for pain perception. Trigeminal nerve is the fifth cranial nerve and it receives pain sensation from oro- and craniofacial region and sends the information up to cortex. Recent investigations demonstrate another important role of cortical neurons in addition to pain perception, that is, corticotrigeminal (cortex to trigeminal) pathway excites neurons in the trigeminal nerve that leads to decrease in the pain response induced by noxious stimuli. Thus, as this mechanism can be induced at early stage of nociception, it may reduce the pain sensation. So, the corticotrigeminal pathway could be a new potential target for pain therapies. This short review revisits the concepts how stimulation of primary somatosensory cortex can be transmitted via corticotrigeminal tract which aim for the inhibitory neurons in spinal trigeminal nucleus caudalis (SpVc) and thus potentially generate a feedforward inhibition, explaining the pain modulatory role of the corticotrigeminal pathway. Mediscope Vol. 7, No. 1: Jan 2020, Page 51-57

scholarly journals Thalamic activity during scalp slow waves in humans

2021 ◽  
Author(s):  
Péter P. Ujma ◽  
Orsolya Szalárdy ◽  
Dániel Fabó ◽  
Loránd Erőss ◽  
Róbert Bódizs
Keyword(s):  
Cortical Neurons ◽  
Large Scale ◽  
Nrem Sleep ◽  
Alpha Activity ◽  
Slow Waves ◽  
Gamma Activity ◽  
Field Potentials ◽  
Thalamic Nuclei ◽  
Time Frequency ◽  
Scalp Eeg

AbstractSlow waves are major pacemakers of NREM sleep oscillations. While slow waves themselves are mainly generated by cortical neurons, it is not clear what role thalamic activity plays in the generation of some oscillations grouped by slow waves, and to what extent thalamic activity during slow waves is itself driven by corticothalamic inputs. To address this question, we simultaneously recorded both scalp EEG and local field potentials from six thalamic nuclei (bilateral anterior, mediodorsal and ventral anterior) in fifteen epileptic patients (age-range: 17-64 years, 7 females) undergoing Deep Brain Stimulation Protocol and assessed the temporal evolution of thalamic activity relative to scalp slow waves using time-frequency analysis. We found that thalamic activity in all six nuclei during scalp slow waves is highly similar to what is observed on the scalp itself. Slow wave downstates are characterized by delta, theta and alpha activity and followed by beta, high sigma and low sigma activity during subsequent upstates. Gamma activity in the thalamus is not significantly grouped by slow waves. Theta and alpha activity appeared first on the scalp, but sigma activity appeared first in the thalamus. These effects were largely independent from the scalp region in which SWs were detected and the precise identity of thalamic nuclei. Our results indicate that while small thalamocortical neuron assemblies may initiate cortical oscillations, especially in the sleep spindle range, the large-scale neuronal activity in the thalamus which is detected by field potentials is principally driven by global cortical activity, and thus it is highly similar to what is observed on the scalp.

scholarly journals Schizophrenia-associated variation at ZNF804A correlates with altered experience-dependent dynamics of sleep slow-waves and spindles in healthy young adults

2020 ◽  
Author(s):  
Ullrich Bartsch ◽  
Laura J Corbin ◽  
Charlotte Hellmich ◽  
Michelle Taylor ◽  
Kayleigh E Easey ◽  
...  
Keyword(s):  
Slow Wave ◽  
Memory Consolidation ◽  
Neural Circuit ◽  
Activity Patterns ◽  
Nrem Sleep ◽  
Slow Waves ◽  
Network Activity ◽  
Healthy Population ◽  
Adult Males ◽  
Performance Improvements

ABSTRACTBackgroundThe rs1344706 polymorphism in ZNF804A is robustly associated with schizophrenia (SZ), yet brain and behavioral phenotypes related to this variant have not been extensively characterized. In turn, SZ is associated with abnormal non-rapid eye movement (NREM) sleep neurophysiology. To examine whether rs1344706 is associated with intermediate neurophysiological traits in the absence of disease, we assessed the relationship between genotype, sleep neurophysiology, and sleep-dependent memory consolidation in healthy participants.MethodsWe recruited healthy adult males, with no history of psychiatric disorder, from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Participants were homozygous for either the SZ-associated ‘A’ allele (N=25) or the alternative ‘C’ allele (N=22) at rs1344706. Actigraphy, polysomnography (PSG) and a motor sequencing task (MST) were used to characterize daily activity patterns, sleep neurophysiology and sleep-dependent memory consolidation.ResultsAverage MST learning and sleep-dependent performance improvements were similar across genotype groups, but with increased variability in the AA group. CC participants showed increased slow-wave and spindle amplitudes, plus augmented coupling of slow-wave activity across recording electrodes after learning. Slow-waves and spindles in those with the AA genotype were insensitive to learning, whilst slow-wave coherence decreased following MST training.ConclusionWe describe evidence that rs1344706 polymorphism in ZNF804A is associated with changes in experience- and sleep-dependent, local and distributed neural network activity that supports offline information processing during sleep in a healthy population. These findings highlight the utility of sleep neurophysiology in mapping the impacts of SZ-associated variants on neural circuit oscillations and function.

scholarly journals Integrity of corpus callosum is essential for the cross-hemispheric propagation of sleep slow waves: a high-density EEG study in split-brain patients

2019 ◽  
Author(s):  
Giulia Avvenuti ◽  
Giacomo Handjaras ◽  
Monica Betta ◽  
Jacinthe Cataldi ◽  
Laura Sophie Imperatori ◽  
...  
Keyword(s):  
Wave Propagation ◽  
White Matter ◽  
Corpus Callosum ◽  
Slow Wave ◽  
Nrem Sleep ◽  
High Density ◽  
Slow Waves ◽  
Wave Parameter ◽  
P Value ◽  
The Cross

AbstractThe slow waves of NREM-sleep (0.5-4Hz) reflect experience-dependent plasticity and play a direct role in the restorative functions of sleep. Importantly, slow waves behave as traveling waves and their propagation is assumed to reflect the structural properties of white matter connections. Based on this assumption, the corpus callosum (CC) may represent the main responsible for cross-hemispheric slow wave propagation. To verify this hypothesis, here we studied a group of patients who underwent total callosotomy due to drug-resistant epilepsy. Overnight high-density (hd)-EEG recordings (256 electrodes) were performed in five totally callosotomized in-patients (CP; 40-53y, 2F), in three control non-callosotomized neurological in-patients (NP; 44-66y, 2F, 1M epileptic), and in an additional sample of 24 healthy adult subjects (HS; 20-47y, 13F). Data were inspected to select NREM-sleep epochs and artefactual or non-physiological activity was rejected. Slow waves were detected using an automated algorithm and their properties and propagation patterns were computed. For each slow wave parameter and for each patient, the relative z-score and the corresponding p-value were calculated with respect to the distribution represented by the HS-group. Group differences were considered significant only when a Bonferroni corrected P < 0.05 was observed in all the CP and in none of the NP. A regression-based adjustment was used to exclude potential confounding effects of age. Slow wave density, amplitude, slope and propagation speed did not differ across CP and HS. In all CP slow waves displayed a significantly reduced probability of cross-hemispheric propagation and a stronger inter-hemispheric asymmetry. Moreover, we found that the incidence of large slow waves tended to differ across hemispheres within individual NREM epochs, with a relative predominance of the right over the left hemisphere in both CP and HS. The absolute magnitude of this inter-hemispheric difference was significantly greater in CP relative to HS. This effect did not depend on differences in slow wave origin within each hemisphere across groups. Present results indicate that the integrity of the CC is essential for the cross-hemispheric traveling of sleep slow waves, supporting the assumption of a direct relationship between white matter structural integrity and cross-hemispheric slow wave propagation. Our findings also imply a prominent role of cortico-cortical connections, rather than cortico-subcortico-cortical loops, in slow wave cross-hemispheric synchronization. Finally, this data indicate that the lack of the CC does not lead to differences in sleep depth, in terms of slow wave generation/origin, across brain hemispheres.

Sign in / Sign up

Export Citation Format

Share Document