Slow-wave Oscillations Research Articles

Somatovisceral intersystemic interactions in newborn rat pups under decreased motor activity

Interaction of slow-wave rhythmic components of cardiac, respiratory and motor activities was investigated in newborn rat pups on the first day after birth under normal conditions and after pharmacological depression of spontaneous periodic motor activity (SPMA) induced by injection of myocuran (myanesin) at low (100 mg/pg, i/p) and maximal (235 mg/pg, i/p) doses. The data obtained indicate that in rat pups after birth the intersystemic interactions are realized mainly via slow-wave oscillations of the near-minute or multiminute ranges, whereas the rhythms of the decasecond range do not play a significant role in integrative processes. Injection of myocuran at a dose causing neither muscle relaxation nor inhibition of motor activity induces changes in the cardiac and respiratory rhythms as well as a transitory decrease in the magnitude of coordinating relations mediated by the rhythms of the near-minute and multiminute ranges. The consequences of myorelaxant injection were found to be more significant for intersystemic interactions with the involvement of the respiratory system. The increase in the myocuran dose and, correspondingly, complete inhibition of SPMA is accompanied by the reduction in the slow-wave components of the pattern of cardiac and respiratory rhythms. The cardiorespiratory interactions, more pronounced in intact rat pups, decrease in the near-minute and multiminute modulation ranges and increase insignificantly in the decasecond modulation range.

Characterization of in utero valproic acid mouse model of autism by local field potential in the hippocampus and the olfactory bulb

Valproic acid (VPA) mouse model of autism spectrum disorder (ASD) has been characterized mostly by impaired ultrasonic vocalization, poor sociability and increased repetitive self-grooming behavior. However, its neural signaling remained unknown. This study investigated the local field potentials (LFPs) in the dorsal hippocampal CA1 and the olfactory bulb while animals exploring a novel open field. VPA was administered at gestational day 13. The results demonstrated three core features of ASD in male offspring. However, there was no difference in Y-maze performance and locomotor activity. Analysis of hippocampal LFP power revealed significantly increased slow wave (1–4Hz) and high gamma (80–140Hz) oscillations and decreased theta (4–12Hz) activity in VPA mice. In the olfactory bulb, VPA animals showed greater slow wave (1–4Hz) and beta (25–40Hz) activity and lower activity of low gamma (55–80Hz) wave. Regression analysis revealed positive correlations between hippocampal theta power and locomotor speed for both control and VPA-exposed mice. There was no significant difference between groups for modulation index of theta (4–12Hz) phase modulated gamma (30–200Hz) amplitude. These findings characterized VPA mouse model with LFP oscillations that might provide better understanding of neural processing in ASD.

Slow-wave oscillations in a corticothalamic model of sleep and wake

A physiologically-based corticothalamic neural field model is used to study slow wave oscillations including cortical UP and DOWN states in deep sleep by extending it to incorporate bursting dynamics of neurons in the thalamic reticular nucleus. The interplay of local bursting dynamics and network interactions produces the cortical UP and DOWN states of slow wave sleep while preserving previously verified model predictions in the wake state. Results show that EEG spectral features in wake and sleep are reproduced. The bursting is subthreshold but acts to intensify the amplitude of oscillations in slow wave sleep with deep UP/DOWN oscillations on the cortex emerging naturally. Furthermore, there is a continuous cycle between the two regimes, rather than a flip-flop between discrete states.

EEG slow-wave coherence changes in propofol-induced general anesthesia: experiment and theory.

The electroencephalogram (EEG) patterns recorded during general anesthetic-induced coma are closely similar to those seen during slow-wave sleep, the deepest stage of natural sleep; both states show patterns dominated by large amplitude slow waves. Slow oscillations are believed to be important for memory consolidation during natural sleep. Tracking the emergence of slow-wave oscillations during transition to unconsciousness may help us to identify drug-induced alterations of the underlying brain state, and provide insight into the mechanisms of general anesthesia. Although cellular-based mechanisms have been proposed, the origin of the slow oscillation has not yet been unambiguously established. A recent theoretical study by Steyn-Ross et al. (2013) proposes that the slow oscillation is a network, rather than cellular phenomenon. Modeling anesthesia as a moderate reduction in gap-junction interneuronal coupling, they predict an unconscious state signposted by emergent low-frequency oscillations with chaotic dynamics in space and time. They suggest that anesthetic slow-waves arise from a competitive interaction between symmetry-breaking instabilities in space (Turing) and time (Hopf), modulated by gap-junction coupling strength. A significant prediction of their model is that EEG phase coherence will decrease as the cortex transits from Turing–Hopf balance (wake) to Hopf-dominated chaotic slow-waves (unconsciousness). Here, we investigate changes in phase coherence during induction of general anesthesia. After examining 128-channel EEG traces recorded from five volunteers undergoing propofol anesthesia, we report a significant drop in sub-delta band (0.05–1.5 Hz) slow-wave coherence between frontal, occipital, and frontal–occipital electrode pairs, with the most pronounced wake-vs.-unconscious coherence changes occurring at the frontal cortex.

Neuronal plasticity during sleep slow wave oscillations

Sleep is critical for regulation of synaptic efficacy, consolidation of memories and learning. It has been proposed that synaptic plasticity associated with sleep rhythms could contribute to consolidation of memories acquired during wakefulness. It was suggested that in the active state of sleep slow wave oscillation, the hippocampal formation activates latent memories stored in the neocortex (replay) and induce permanent changes in synaptic conductances. In this study, we present a thalamocortical network model of the slow-wave sleep activity characterized by repeatable (< 1 Hz) transitions between active (Up) and silent (Down) states of the network. The model consisted a layer of thalamic relay (TC) and reticular (RE) neurons in the thalamus as well as a model of cortical column with pyramidal neurons and inhibitory interneurons. All neurons were modeled based on the Hodgkin-Huxley kinetics. Spike-timing dependent synaptic plasticity was implemented to regulate synaptic efficacy. The slow oscillation was driven by intracortical dynamics; active states were initiated by the spontaneous miniature synaptic releases at different network sites [1] and propagated within the cortical network. The properties of slow oscillations depended on the intrinsic conductances, miniature synaptic releases, and the synaptic strength. In agreement with previous experimental studies, transition from the active to the silent state occurred more synchronously than the active state initiation. We found that the pattern of the active state propagation depended on the spatiotemporal pattern of activity on the previous cycle of slow oscillation and could be influenced by external input. Because of the refractoriness properties of the network, a probability of the next active state initiation was higher for the network site that initiated activity at the previous cycle. Furthermore, even weak external stimulation delivered to the network results in increase probability of up-state induction at the stimulation location. This suggests that spatially and temporally sparse hippocampal input could influence the spatiotemporal pattern of slow oscillation. Location of the initiation site and the pattern of active state propagation determined the relative timing of spiking in cortical neurons. When spike-time dependent synaptic plasticity (STDP) was implemented, there was a net decrease in synaptic strengths and, at the same time, an increase in the strength of specific synapses which were associated with the sequence replay. The change in synaptic weights between any two neurons was determined by the direction of active state propagation and by the distance between the neurons. Our study propose a mechanism of how interaction between cortically generated slow waves and sparse external input, possibly representing input from hippocampal formation, may lead to reorganization of synaptic strength during stage 3/4 sleep.

Hippocampal replay and cortical slow oscillations: a computational study

Sleep is known to be important for memory consolidation [1], and memories are thought to be stored in the hippocampus during the wakefulness and “transferred” to cortex during sleep [2]. Recently, memory replay – repeatable sequences of pyramidal cell firing – has been demonstrated during sleep, and associated with characteristic brain oscillations, giving rise to the hypothesis that these may form the critical neural substrate of memory consolidation. Tampering with replay can disrupt memory formation and consolidation [3], and the mechanisms underlying sequence replay are still unknown. During sleep, replay events are associated with specific patterns of neuronal activity. Replay is seen in cortex during sleep oscillation – a rhythmic ( 150 Hz) firing [4]. It is believed that hippocampal ripples may contribute to the cortical active state generation, however specific interactions between ripples and slow oscillation remain unknown. In the present study, build on our previous research [5], we develop a model of ripple generation to explore interaction between cortical slow oscillation and hippocampal ripples during sleep. Data suggest that during ripple events only a few pyramidal (excitatory) cells are recruited in CA1, and they spike at the peak of the event, while perisomatic interneurons (a kind of inhibitory cells) spike across the duration of the event [6]. The distribution of spike timing with respect to ripple peak is different for different types of interneurons. In hippocampal area CA1, axo-axonic cells tend to spike at ripple initiation and be suppressed in the later part of a ripple [7]. Since axo-axonic cells are in a crucial position to suppress the spikes of the pyramidal cell they impinge upon, we hypothesize that they can regulate the initiation of specific cell activity replay. In this study we designed a computational model of ripple generation that emphasizes the role of axo-axonic cells in selecting which pyramidal cells are participating in ripple activity, hence what sequence is replayed during a given ripple. In our model, high-frequency firing of the perisomatic interneurons mediate high-frequency LFP oscillations in pyramidal neurons while axo-axonic interneurons define specific sequence of pyramidal cell firing. Using such model, we investigate the timing relationship between cortical slow-wave oscillations and hippocampal ripples. Our study proposes a novel mechanism of hippocampal ripple generation and predicts how interactions between different electrographic events during sleep may contribute to coordinated replay in cortical and hippocampal networks.

Resting-state slow wave power, healthy aging and cognitive performance.

Cognitive functions and spontaneous neural activity show significant changes over the life-span, but the interrelations between age, cognition and resting-state brain oscillations are not well understood. Here, we assessed performance on the Trail Making Test and resting-state magnetoencephalographic (MEG) recordings from 53 healthy adults (18–89 years old) to investigate associations between age-dependent changes in spontaneous oscillatory activity and cognitive performance. Results show that healthy aging is accompanied by a marked and linear decrease of resting-state activity in the slow frequency range (0.5–6.5 Hz). The effects of slow wave power on cognitive performance were expressed as interactions with age: For older (>54 years), but not younger participants, enhanced delta and theta power in temporal and central regions was positively associated with perceptual speed and executive functioning. Consistent with previous work, these findings substantiate further the important role of slow wave oscillations in neurocognitive function during healthy aging.

Change of character of intersystemic interactions in newborn rat pups under conditions of a decrease of central influences (urethane anesthesia)

On newborn rat pups, for the first day after birth, there was studied the character of mutual influences between the slow-wave rhythmical components of the cardiac, respiratory, and motor activities reflecting interactions between the main functional systems of the developing organism. The study was carried out in norm and after pharmacological depression of the spontaneous periodical motor activity (SPMA) performed by narcotization of rat pups with urethane at low (0.5 g/kg, i/p) and maximal (1 g/kg, i/p) doses. Based on the complex of our obtained data, it is possible to conclude that after birth in rat pups the intersystemic interactions are realized mainly by the slow-wave oscillations of the near- and manyminute diapason. The correlational interactions mediated by rhythms of the decasecond diapason do not play essential role in integrative processes. Injection to the animals of urethane producing selective suppression of reaction of consciousness, but not affecting activating influences of reticular formation on cerebral cortex does not cause marked changes of autonomous parameters, but modulates structure and expression of spontaneous periodical motor activity. There occurs an essential decrease of mutual influences between motor and cardiovascular systems. In the case of preservation of motor activity bursts, a tendency for enhancement of correlational relations between the modulating rhythms of motor and somatomotor systems is observed. The cardiorespiratory interactions, more pronounced in intact rat pups in the near- and many-minute modulation diapason, under conditions of urethane, somewhat decrease, whereas the rhythmical components of the decasecond diapason--are weakly enhanced.

Slaves to the rhythm: coupling of the subthalamic nucleus–globus pallidus network in Parkinsonian oscillations

Slaves to the rhythm: coupling of the subthalamic nucleus–globus pallidus network in Parkinsonian oscillations

The role of linear and voltage-dependent ionic currents in the generation of slow wave oscillations

Neuronal oscillatory activity is generated by a combination of ionic currents, including at least one inward regenerative current that brings the cell towards depolarized voltages and one outward current that repolarizes the cell. Such currents have traditionally been assumed to require voltage-dependence. Here we test the hypothesis that the voltage dependence of the regenerative inward current is not necessary for generating oscillations. Instead, a current I NL that is linear in the biological voltage range and has negative conductance is sufficient to produce regenerative activity. The current I NL can be considered a linear approximation to the negative-conductance region of the current-voltage relationship of a regenerative inward current. Using a simple conductance-based model, we show that I NL , in conjunction with a voltage-gated, non-inactivating outward current, can generate oscillatory activity. We use phase-plane and bifurcation analyses to uncover a rich variety of behaviors as the conductance of I NL is varied, and show that oscillations emerge as a result of destabilization of the resting state of the model neuron. The model shows the need for well-defined relationships between the inward and outward current conductances, as well as their reversal potentials, in order to produce stable oscillatory activity. Our analysis predicts that a hyperpolarization-activated inward current can play a role in stabilizing oscillatory activity by preventing swings to very negative voltages, which is consistent with what is recorded in biological neurons in general. We confirm this prediction of the model experimentally in neurons from the crab stomatogastric ganglion.

Quantitative estimation of connection of the heart rate rhythm with motor activity in rat fetuses

In rat fetuses at E17-20 with preserved placental circulation with use of mathematical analysis there were revealed value and character of connections of slow wave oscillations of the heart rhythm with motor activity for 30 min of observation. In the software "PowerGraph 3.3.8", normalization and filtration of the studied signals were performed at three frequency diapasons: D1 - 0.02-0.2 Hz (5-50 s), D2 - 0.0083-0.02 Hz (50 s-2 min), and D3 - 0.0017-0.0083 Hz (2-10 min). The EMG curves filtrated by diapasons or piezograms were compared with periodograms in the corresponding diapasons of the heart rhythm variations. In the software "Origin 8.0", quantitative estimation of the degree of intersystemic interrelations for each frequency diapason was performed by Pearson correlation of coefficient, by the correlation connection value, and by the time shift of maximum of cross-correlation function. It has been established that in the frequency D1, regardless of age, the connection of heart rhythm oscillations with motor activity is expressed weakly. In the frequency diapason D2, the connection in most cases is located in the zone of weak and moderate correlations. In the multiminute diapason (D3), the connection is more pronounced. The number of animals that have a significant value of the correlation connection rises. The fetal MA fires in the decasecond diapason in all age groups are accompanied by short-time decelerations of the heart rhythms. In the minute diapason, there is observed a transition from positive connections at E17 and E18 to the negative ones at E19-20. Results of the study are considered in association with age-related changes of ratios of positive and negative oscillations of the heart rhythm change depending on the character of motor activity.

Analysis of slow wave oscillations in cerebral haemodynamics and metabolism following subarachnoid haemorrhage.

Aneurysmal subarachnoid haemorrhage (SAH) causes the greatest loss of productive life years of any form of stroke. Emerging concepts of pathophysiology highlight early abnormalities of microvascular function, including impaired autoregulation of cerebral blood flow and flow-metabolism coupling, as key causes of cerebral ischaemia and poor outcome. Near infrared spectroscopy (NIRS) is a non-invasive optical technique which may help identify cerebral microvascular dysfunction. The aim of this research is to investigate the status of flow-metabolism coupling by examining phase relationships between NIRS-derived concentrations of oxy-haemoglobin ([HbO2]), deoxy-haemoglobin ([HHb]) and cytochrome c oxidase oxidation ([oxCCO]). Eight sedated ventilated patients with SAH were investigated. A combined NIRS broadband and frequency domain spectroscopy system was used to measure [HbO2], [HHb] and [oxCCO] alongside other multimodal neuromonitoring. Wavelet analysis of phase relationships revealed antiphase [HbO2]-[oxCCO] and in-phase [HbO2]-[HHb] oscillations between 0.1Hz-0.01Hz consistent with compromised flow-metabolism coupling. NIRS derived variables might offer unique insights into microvascular and metabolic dysfunction following SAH, and in the future identify therapeutic windows or targets.

Acute effect of carbamazepine on corticothalamic 5-9-Hz and thalamocortical spindle (10-16-Hz) oscillations in the rat

A major side effect of carbamazepine (CBZ), a drug used to treat neurological and neuropsychiatric disorders, is drowsiness, a state characterized by increased slow-wave oscillations with the emergence of sleep spindles in the electroencephalogram (EEG). We conducted cortical EEG and thalamic cellular recordings in freely moving or lightly anesthetized rats to explore the impact of CBZ within the intact corticothalamic (CT)-thalamocortical (TC) network, more specifically on CT 5-9-Hz and TC spindle (10-16-Hz) oscillations. Two to three successive 5-9-Hz waves were followed by a spindle in the cortical EEG. A single systemic injection of CBZ (20 mg/kg) induced a significant increase in the power of EEG 5-9-Hz oscillations and spindles. Intracellular recordings of glutamatergic TC neurons revealed 5-9-Hz depolarizing wave-hyperpolarizing wave sequences prolonged by robust, rhythmic spindle-frequency hyperpolarizing waves. This hybrid sequence occurred during a slow hyperpolarizing trough, and was at least 10 times more frequent under the CBZ condition than under the control condition. The hyperpolarizing waves reversed at approximately -70 mV, and became depolarizing when recorded with KCl-filled intracellular micropipettes, indicating that they were GABAA receptor-mediated potentials. In neurons of the GABAergic thalamic reticular nucleus, the principal source of TC GABAergic inputs, CBZ augmented both the number and the duration of sequences of rhythmic spindle-frequency bursts of action potentials. This indicates that these GABAergic neurons are responsible for the generation of at least the spindle-frequency hyperpolarizing waves in TC neurons. In conclusion, CBZ potentiates GABAA receptor-mediated TC spindle oscillations. Furthermore, we propose that CT 5-9-Hz waves can trigger TC spindles.

Structural brain correlates of human sleep oscillations

Sleep is strongly conserved within species, yet marked and perplexing inter-individual differences in sleep physiology are observed. Combining EEG sleep recordings and high-resolution structural brain imaging, here we demonstrate that the morphology of the human brain offers one explanatory factor of such inter-individual variability. Gray matter volume in interoceptive and exteroceptive cortices correlated with the expression of slower NREM sleep spindle frequencies, supporting their proposed role in sleep protection against conscious perception. Conversely, and consistent with an involvement in declarative memory processing, gray matter volume in bilateral hippocampus was associated with faster NREM sleep spindle frequencies. In contrast to spindles, gray matter volume in the homeostatic sleep-regulating center of the basal forebrain/hypothalamus, together with the medial prefrontal cortex, accounted for individual differences in NREM slow wave oscillations. Together, such findings indicate that the qualitative and quantitative expression of human sleep physiology is significantly related to anatomically specific differences in macroscopic brain structure.

Individual Differences in Inhibitory Control—Relationship Between Baseline Activation in Lateral PFC and an Electrophysiological Index of Response Inhibition

The capacity to inhibit inappropriate responses is crucial for goal-directed behavior. Inhibiting such responses seems to come more easily to some of us than others, however. From where do these individual differences originate? Here, we measured 263 participants' neural baseline activation using resting electroencephalogram. Then, we used this stable neural marker to predict a reliable electrophysiological index of response inhibition capacity in the cued Continuous Performance Test, the NoGo-Anteriorization (NGA). Using a source-localization technique, we found that resting delta, theta, and alpha1 activity in the left middle frontal gyrus and resting alpha1 activity in the right inferior frontal gyrus were negatively correlated with the NGA. As a larger NGA is thought to represent better response inhibition capacity, our findings demonstrate that lower levels of resting slow-wave oscillations in the lateral prefrontal cortex, bilaterally, are associated with a better response inhibition capacity.

Transcranial electrical stimulation accelerates human sleep homeostasis.

The sleeping brain exhibits characteristic slow-wave activity which decays over the course of the night. This decay is thought to result from homeostatic synaptic downscaling. Transcranial electrical stimulation can entrain slow-wave oscillations (SWO) in the human electro-encephalogram (EEG). A computational model of the underlying mechanism predicts that firing rates are predominantly increased during stimulation. Assuming that synaptic homeostasis is driven by average firing rates, we expected an acceleration of synaptic downscaling during stimulation, which is compensated by a reduced drive after stimulation. We show that 25 minutes of transcranial electrical stimulation, as predicted, reduced the decay of SWO in the remainder of the night. Anatomically accurate simulations of the field intensities on human cortex precisely matched the effect size in different EEG electrodes. Together these results suggest a mechanistic link between electrical stimulation and accelerated synaptic homeostasis in human sleep.

Slow wave activity and slow oscillations in sleepwalkers and controls: effects of 38 h of sleep deprivation

Sleepwalkers have been shown to have an unusually high number of arousals from slow wave sleep and lower slow wave activity (SWA) power during the night than controls. Because sleep deprivation increases the frequency of slow wave sleep (SWS) arousals in sleepwalkers, it may also affect the expression of the homeostatic process to a greater extent than shown previously. We thus investigated SWA power as well as slow wave oscillation (SWO) density in 10 sleepwalkers and nine controls at baseline and following 38h of sleep deprivation. There was a significant increase in SWA during participants' recovery sleep, especially during their second non-rapid eye movement (NREM) period. SWO density was similarly increased during recovery sleep's first two NREM periods. A fronto-central gradient in SWA and SWO was also present on both nights. However, no group differences were noted on any of the 2 nights on SWA or SWO. This unexpected result may be related to the heterogeneity of sleepwalkers as a population, as well as our small sample size. SWA pressure after extended sleep deprivation may also result in a ceiling effect in both sleepwalkers and controls.

Visual experience and subsequent sleep induce sequential plastic changes in putative inhibitory and excitatory cortical neurons

Ocular dominance plasticity in the developing primary visual cortex is initiated by monocular deprivation (MD) and consolidated during subsequent sleep. To clarify how visual experience and sleep affect neuronal activity and plasticity, we continuously recorded extragranular visual cortex fast-spiking (FS) interneurons and putative principal (i.e., excitatory) neurons in freely behaving cats across periods of waking MD and post-MD sleep. Consistent with previous reports in mice, MD induces two related changes in FS interneurons: a response shift in favor of the closed eye and depression of firing. Spike-timing-dependent depression of open-eye-biased principal neuron inputs to FS interneurons may mediate these effects. During post-MD nonrapid eye movement sleep, principal neuron firing increases and becomes more phase-locked to slow wave and spindle oscillations. Ocular dominance (OD) shifts in favor of open-eye stimulation--evident only after post-MD sleep--are proportional to MD-induced changes in FS interneuron activity and to subsequent sleep-associated changes in principal neuron activity. OD shifts are greatest in principal neurons that fire 40-300 ms after neighboring FS interneurons during post-MD slow waves. Based on these data, we propose that MD-induced changes in FS interneurons play an instructive role in ocular dominance plasticity, causing disinhibition among open-eye-biased principal neurons, which drive plasticity throughout the visual cortex during subsequent sleep.

Disruption of interstitial cells of Cajal networks after massive small bowel resection

To investigate the disruptions of interstitial cells of Cajal (ICC) in the remaining bowel in rats after massive small bowel resection (mSBR). Thirty male Sprague-Dawley rats fitting entry criteria were divided randomly into three experimental groups (n = 10 each): Group A rats underwent bowel transection and re-anastomosis (sham) and tissue samples were harvested at day 7 post-surgery. Group B and C rats underwent 80% small bowel resection with tissue harvested from Group B rats at day 7 post-surgery, and from Group C rats at day 14 post-surgery. The distribution of ICC at the site of the residual small bowel was evaluated by immunohistochemical analysis of small intestine samples. The ultrastructural changes of ICC in the remnant ileum of model rats 7 and 14 d after mSBR were analyzed by transmission electron microscopy. Intracellular recordings of slow wave oscillations were used to evaluate electrical pacemaking. The protein expression of c-kit, ICC phenotypic markers, and membrane-bound stem cell factor (mSCF) in intestinal smooth muscle of each group were detected by Western blotting. After mSBR, immunohistochemical analysis indicated that the number of c-kit-positive cells was dramatically decreased in Group B rats compared with sham tissues. Significant ultrastructural changes in ICC with associated smooth muscle hypertrophy were also observed. Disordered spontaneous rhythmic contractions with reduced amplitude (8.5 ± 1.4 mV vs 24.8 ± 1.3 mV, P = 0.037) and increased slow wave frequency (39.5 ± 2.1 cycles/min vs 33.0 ± 1.3 cycles/min, P = 0.044) were found in the residual intestinal smooth muscle 7 d post mSBR. The contractile function and electrical activity of intestinal circular smooth muscle returned to normal levels at 14 d post mSBR (amplitude, 14.9 ± 1.6 mV vs 24.8 ± 1.3 mV; frequency, 30.7 ± 1.7 cycles/min vs 33.0 ± 1.3 cycles/min). The expression of Mscf and c-kit protein was decreased at 7 d (P = 0.026), but gradually returned to normal levels at 14 d. The ICC and associated neural networks were disrupted, which was associated with the phenotype alterations of ICC. Massive small bowel resection in rats triggered damage to ICC networks and decreased the number of ICC leading to disordered intestinal rhythmicity. The mSCF/c-kit signaling pathway plays a role in the regulation and maintenance of ICC phenotypes.

Effects of weak transcranial alternating current stimulation on brain activity—a review of known mechanisms from animal studies

Rhythmic neuronal activity is ubiquitous in the human brain. These rhythms originate from a variety of different network mechanisms, which give rise to a wide-ranging spectrum of oscillation frequencies. In the last few years an increasing number of clinical research studies have explored transcranial alternating current stimulation (tACS) with weak current as a tool for affecting brain function. The premise of these interventions is that tACS will interact with ongoing brain oscillations. However, the exact mechanisms by which weak currents could affect neuronal oscillations at different frequency bands are not well known and this, in turn, limits the rational optimization of human experiments. Here we review the available in vitro and in vivo animal studies that attempt to provide mechanistic explanations. The findings can be summarized into a few generic principles, such as periodic modulation of excitability, shifts in spike timing, modulation of firing rate, and shifts in the balance of excitation and inhibition. These effects result from weak but simultaneous polarization of a large number of neurons. Whether this can lead to an entrainment or a modulation of brain oscillations, or whether AC currents have no effect at all, depends entirely on the specific dynamic that gives rise to the different brain rhythms, as discussed here for slow wave oscillations (∼1 Hz) and gamma oscillations (∼30 Hz). We conclude with suggestions for further experiments to investigate the role of AC stimulation for other physiologically relevant brain rhythms.