Desynchronizing Effect Research Articles

Diazepam and ethanol differently modulate neuronal activity in organotypic cortical cultures

BackgroundThe pharmacodynamic results of diazepam and ethanol administration are similar, in that each can mediate amnestic and sedative-hypnotic effects. Although each of these molecules effectively reduce the activity of central neurons, diazepam does so through modulation of a more specific set of receptor targets (GABAA receptors containing a γ-subunit), while alcohol is less selective in its receptor bioactivity. Our investigation focuses on divergent actions of diazepam and ethanol on the firing patterns of cultured cortical neurons.MethodWe used electrophysiological recordings from organotypic slice cultures derived from Sprague–Dawley rat neocortex. We exposed these cultures to either diazepam (15 and 30 µM, n = 7) or ethanol (30 and 60 mM, n = 11) and recorded the electrical activity at baseline and experimental conditions. For analysis, we extracted the episodes of spontaneous activity, i.e., cortical up-states. After separation of action potential and local field potential (LFP) activity, we looked at differences in the number of action potentials, in the spectral power of the LFP, as well as in the coupling between action potential and LFP phase.ResultsWhile both substances seem to decrease neocortical action potential firing in a not significantly different (p = 0.659, Mann–Whitney U) fashion, diazepam increases the spectral power of the up-state without significantly impacting the spectral composition, whereas ethanol does not significantly change the spectral power but the oscillatory architecture of the up-state as revealed by the Friedman test with Bonferroni correction (p < 0.05). Further, the action potential to LFP-phase coupling reveals a synchronizing effect of diazepam for a wide frequency range and a narrow-band de-synchronizing effect for ethanol (p < 0.05, Kolmogorov–Smirnov test).ConclusionDiazepam and ethanol, induce specific patterns of network depressant actions. Diazepam induces cortical network inhibition and increased synchronicity via gamma subunit containing GABAA receptors. Ethanol also induces cortical network inhibition, but without an increase in synchronicity via a wider span of molecular targets.

Bi-stability resistant to fluctuations

We study a simple micro-mechanical device that does not lose its snap-through behavior in an environment dominated by fluctuations. The main idea is to have several degrees of freedom that can cooperatively resist the de-synchronizing effect of random perturbations. As an inspiration we use the power stroke machinery of skeletal muscles, which ensures at sub-micron scales and finite temperatures a swift recovery of an abruptly applied slack. In addition to hypersensitive response at finite temperatures, our prototypical Brownian snap spring also exhibits criticality at special values of parameters which is another potentially interesting property for micro-scale engineering applications.

Has Globalization Really Increased Business Cycle Synchronization?

This paper assesses the strength of business cycle synchronization between 1950 and 2014 in a sample of 21 countries using a new quarterly dataset based on IMF archival data. Contrary to the common wisdom, we find that the globalization period is not associated with more output synchronization at the global level. The world business cycle was as strong during Bretton Woods (1950-1971) than during the Globalization period (1984-2006). Although globalization did not affect the average level of co-movement, trade and financial integration strongly affect the way countries co-move with the rest of the world. We find that financial integration de-synchronizes national outputs from the world cycle, although the magnitude of this effect depends crucially on the type of shocks hitting the world economy. This de-synchronizing effect has offset the synchronizing impact of other forces, such as increased trade integration.

Has Globalization Really Increased Business Cycle Synchronization?

This paper assesses the strength of business cycle synchronization between 1950 and 2014 in a sample of 21 countries using a new quarterly dataset based on IMF archival data. Contrary to the common wisdom, we find that the globalization period is not associated with more output synchronization at the global level. The world business cycle was as strong during Bretton Woods (1950-1971) than during the Globalization period (1984-2006). Although globalization did not affect the average level of co-movement, trade and financial integration strongly affect the way countries co-move with the rest of the world. We find that financial integration de-synchronizes national outputs from the world cycle, although the magnitude of this effect depends crucially on the type of shocks hitting the world economy. This de-synchronizing effect has offset the synchronizing impact of other forces, such as increased trade integration

Has Globalization Really Increased Business Cycle Synchronization?

This paper assesses the strength of business cycle synchronization between 1950 and 2014 in a sample of 21 countries using a new quarterly dataset based on IMF archival data. Contrary to the common wisdom, we find that the globalization period is not associated with more output synchronization at the global level. The world business cycle was as strong during Bretton Woods (1950-1971) than during the Globalization period (1984-2006). Although globalization did not affect the average level of co-movement, trade and financial integration strongly affect the way countries co-move with the rest of the world. We find that financial integration de-synchronizes national outputs from the world cycle, although the magnitude of this effect depends crucially on the type of shocks hitting the world economy. This de-synchronizing effect has offset the synchronizing impact of other forces, such as increased trade integration.

Trigeminal stimulation

Seizures are characterized by hypersynchronous neuronal discharges, and desynchronizing stimuli abort and sometimes prevent seizures. The most direct but invasive method has been the application of electrical cortical stimulation at seizure onset. This successful termination of seizures has formed the basis for translational research involving implantable seizure detection and neurostimulation devices. The pioneering work of Moruzzi and Magoun in 19491 demonstrated that stimulation of the ascending reticular activating system (ARAS) can have a desynchronizing effect on cortical rhythms. This system not only projects widely throughout cortex, but also receives collateral input from all sensory systems.

Multiple Factors Influence Calcium Synchronization in Arterial Vasomotion

The intercellular synchronization of spontaneous calcium (Ca2+) oscillations in individual smooth muscle cells is a prerequisite for vasomotion. A detailed mathematical model of Ca2+ dynamics in rat mesenteric arteries shows that a number of synchronizing and desynchronizing pathways may be involved. In particular, Ca2+-dependent phospholipase C, the intercellular diffusion of inositol trisphosphate (IP3, and to a lesser extent Ca2+), IP3 receptors, diacylglycerol-activated nonselective cation channels, and Ca2+-activated chloride channels can contribute to synchronization, whereas large-conductance Ca2+-activated potassium channels have a desynchronizing effect. Depending on the contractile state and agonist concentrations, different pathways become predominant, and can be revealed by carefully inhibiting the oscillatory component of their total activity. The phase shift between the Ca2+ and membrane potential oscillations can change, and thus electrical coupling through gap junctions can mediate either synchronization or desynchronization. The effect of the endothelium is highly variable because it can simultaneously enhance the intercellular coupling and affect multiple smooth muscle cell components. Here, we outline a system of increased complexity and propose potential synchronization mechanisms that need to be experimentally tested.

Changes Across Time in the Temporal Responses of Auditory Nerve Fibers Stimulated by Electric Pulse Trains

Most auditory prostheses use modulated electric pulse trains to excite the auditory nerve. There are, however, scant data regarding the effects of pulse trains on auditory nerve fiber (ANF) responses across the duration of such stimuli. We examined how temporal ANF properties changed with level and pulse rate across 300-ms pulse trains. Four measures were examined: (1) first-spike latency, (2) interspike interval (ISI), (3) vector strength (VS), and (4) Fano factor (FF, an index of the temporal variability of responsiveness). Data were obtained using 250-, 1,000-, and 5,000-pulse/s stimuli. First-spike latency decreased with increasing spike rate, with relatively small decrements observed for 5,000-pulse/s trains, presumably reflecting integration. ISIs to low-rate (250 pulse/s) trains were strongly locked to the stimuli, whereas ISIs evoked with 5,000-pulse/s trains were dominated by refractory and adaptation effects. Across time, VS decreased for low-rate trains but not for 5,000-pulse/s stimuli. At relatively high spike rates (>200 spike/s), VS values for 5,000-pulse/s trains were lower than those obtained with 250-pulse/s stimuli (even after accounting for the smaller periods of the 5,000-pulse/s stimuli), indicating a desynchronizing effect of high-rate stimuli. FF measures also indicated a desynchronizing effect of high-rate trains. Across a wide range of response rates, FF underwent relatively fast increases (i.e., within 100 ms) for 5,000-pulse/s stimuli. With a few exceptions, ISI, VS, and FF measures approached asymptotic values within the 300-ms duration of the low- and high-rate trains. These findings may have implications for designs of cochlear implant stimulus protocols, understanding electrically evoked compound action potentials, and interpretation of neural measures obtained at central nuclei, which depend on understanding the output of the auditory nerve.

Neuronal synchronization of tonically active neurons in the striatum of normal and parkinsonian primates.

1. Previous studies indicate that tonically active neurons (TANs) are the cholinergic interneurons of the striatum and predict that their activity is synchronized. To test whether TANs do fire synchronously, and whether dopamine depletion affects their synchronization, we recorded the simultaneous activity of several TANs in the putamens of two vervet monkeys before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. 2. Cross-correlation analysis revealed that most pairs of TANS (33 of 54; 61.1%) fire synchronously at +/- 60-ms delay. Correlated activity was more common between neurons with characteristic response to reward (17 of 19 pairs; 89.5%). 3. Cross-correlation study of 24 triplets of TANS showed synchronization of spiking activity of all 3 TANS in only 29.2% of cases (7 of 24 triplets). Correlated activity of two of three possible pairs was found in 25% of the cases. 4. After MPTP treatment and the development of parkinsonian symptoms, most TANS' auto- and cross-correlograms (22 of 28 units; 78.6%; and 23 of 28 pairs; 82.1%) became oscillatory. The number of correlated pairs was slightly increased (24 of 28; 85.7%). The strength of the synchronization was not significantly different from the normal values. 5. These findings support the notion that TANs function as distributed, partially overlapping synchronized networks. However, a normal dopaminergic system is not essential for synchronization of TANs; on the contrary, dopaminergic activity may even have a desynchronizing effect on the basal ganglia's system.

Brain and odor: IL EEG activity during nose and mouth breathing

Previous investigations have suggested that low, undetectable concentrations of odor chemicals alter central nervous system (CNS) activity. Since there can be no odor-free environment, room air also may alter CNS activity. To examine this hypothesis, EEG data were recorded from 20 subjects while they inhaled room air through the mouth or the nose. Results of the experiment indicated that EEG alpha activity in the left hemisphere was reduced for individuals inhaling through the nose, and that EEG beta activity showed greater spatial diversity during nose inhalations. These results demonstrate that room air passing through the nose has a desynchroniz-ing effect upon the EEG and may contain odor information not available through mouth inhalation. These results further substantiate the hypothesis that undetected odors markedly alter ongoing CNS activity.

Effect of the standardized Ginseng Extract G115 on the metabolism and electrical activity of the rabbit's brain.

The objective of this original investigation was to study the effect of the standardized Ginseng Extract G115 on the metabolic activity and ECoG of the rabbit's brain. The results showed significant increase of the glucose uptake with simultaneous significant reduction of the lactate, pyruvate and lactate/pyruvate ratio. These findings indicate shift of glucose utilization by the drug from anaerobic to the more economical pathway. G115 was also shown to produce a desynchronizing effect on the electrocorticogram (ECoG) which correlated well with the biochemical findings.

Some electrophysiological and pharmacological properties of the cortical, noradrenergic projection of the locus coeruleus in the rat

The effect of repetitive stimulation of the locus coeruleus (LC) on the discharge rate of spontaneously active neurons of the visual, rostral and cingulate cortex was investigated in untreated and catecholamine-depleted rats under chloral hydrate anesthesia. In untreated animals, the inhibitory transsynaptic effects predominated over the excitatory ones. In catecholamine-depleted rats, the percentage of inhibited cells was significantly reduced in all areas. The vast majority of spontaneously active neurons in all cortical regions was depressed by microiontophoretically applied noradrenaline (NA). A few cells were resistant to NA; no excitatory effects were noticed on any cell. The transsynaptically mediated depression of the discharge rate of cells in all three cortical areas was reversibly antagonized by the iontophoretically administered β-receptor blocking drug practolol. On the contrary the α-receptor blocking drugs piperoxane and WB 4101 were ineffective in this respect. Thus, we tentatively conclude from these data that the NA-elicited depression of cells in the cortex is mediated by a receptor of the β-type. Repetitive stimulation of the reticular formation elicited a desynchronizing effect on the EEG of chloral hydrate anaesthetized rats. LC stimulation, in contrast, hardly produced any modification of the EEG as judged by visual examination of the recordings.

Theta-volleys of neurons of the hippocampus and septum.

1. In the hippocampus of waking unrestrained rabbits neurons with theta-volleys of activity account for 10–14% of the total. In the medial and lateral nuclei of the septum these neurons are more numerous (28–29%) and their theta-volleys are more clearly defined. 2. After removal of the septal input theta-volleys disappear from the unit activity of the hippocampus, and the theta-rhythm disappears from its global electrical activity. 3. After removal of the cortical input the number of neurons with theta-volleys in their discharge increases significantly (to 38–43%). 4. In the nuclei of the septum, deprived of their hippocampal influences, the number of neurons with theta-volleys increases to 48%. Electrical stimulation of the hippocampus inhibits or delays theta-volleys in the septum. 5. Stimulation of RF evokes theta-volleys in the septum and hippocampus. Effects of stimuation show high correlation in both structures with the characteristics of the sensory responses in the same neurons. 6. The presence of theta-volleys in the hippocampus is determined by connections from the septum. The cortical input of the hippocampus has a desynchronizing effect on both single unit activity and on slow global activity of the hippocampus. 7. Theta-volleys in the septum are independent of connections with the hippocampus, which have a desynchronizing effect on it, antagonistic to the action of RF and analogous to the action of the cortical input on the hippocampus.