Increase In Rhythm Research Articles

Decreased but diverse activity of cortical and thalamic neurons in consciousness-impairing rodent absence seizures

Absence seizures are brief episodes of impaired consciousness, behavioral arrest, and unresponsiveness, with yet-unknown neuronal mechanisms. Here we report that an awake female rat model recapitulates the behavioral, electroencephalographic, and cortical functional magnetic resonance imaging characteristics of human absence seizures. Neuronally, seizures feature overall decreased but rhythmic firing of neurons in cortex and thalamus. Individual cortical and thalamic neurons express one of four distinct patterns of seizure-associated activity, one of which causes a transient initial peak in overall firing at seizure onset, and another which drives sustained decreases in overall firing. 40–60 s before seizure onset there begins a decline in low frequency electroencephalographic activity, neuronal firing, and behavior, but an increase in higher frequency electroencephalography and rhythmicity of neuronal firing. Our findings demonstrate that prolonged brain state changes precede consciousness-impairing seizures, and that during seizures distinct functional groups of cortical and thalamic neurons produce an overall transient firing increase followed by a sustained firing decrease, and increased rhythmicity.

Diurnal small RNA expression and post-transcriptional regulation in young and old Drosophila melanogaster heads

Background: MicroRNAs are a class of small (~22nt) endogenous RNAs that regulate target transcript expression post-transcriptionally. Previous studies characterized age-related changes in diurnal transcript expression but it is not understood how these changes are regulated, and whether they may be attributed in part to changes in microRNA expression or activity with age. Diurnal small RNA expression changes with age were not previously studied. Methods: To interrogate changes in small RNA expression with age, we collected young (5 day) and old (55 day) Drosophila melanogaster around-the-clock and performed deep sequencing on size-selected RNA from whole heads. Results: We found several microRNAs with changes in rhythmicity after aging, and we investigated microRNAs which are differentially expressed with age. We found that predicted targets of differentially expressed microRNAs have RNA-binding and transcription factor activity. We used a previously published method to identify mRNA transcripts which show evidence of microRNA targeting that is altered after aging, and found several that are involved in muscle development and maintenance. Finally, we identified novel microRNAs using the random-forest-based method miRWoods, which surprisingly also discovered transfer RNA-derived fragments. Conclusions: We showed a decrease in global microRNA expression and a corresponding increase in piRNA expression during aging. We also found an increase in rhythmicity of Drosophila small RNAs during aging, including microRNAs, piRNA clusters, and novel transfer RNA-derived fragments. To our knowledge this is the first study examining diurnal small RNA expression around the clock in young and old Drosophila, and as such it paves the way for future research on changes in small RNA regulatory molecules in the context of aging.

CAMP-Dependent Signaling Restores AP Firing in Dormant SA Node Cells via Enhancement of Surface Membrane Currents and Calcium Coupling.

Action potential (AP) firing rate and rhythm of sinoatrial nodal cells (SANC) are controlled by synergy between intracellular rhythmic local Ca2+ releases (LCRs) (“Ca2+ clock”) and sarcolemmal electrogenic mechanisms (“membrane clock”). However, some SANC do not fire APs (dormant SANC). Prior studies have shown that β-adrenoceptor stimulation can restore AP firing in these cells. Here we tested whether this relates to improvement of synchronization of clock coupling. We characterized membrane potential, ion currents, Ca2+ dynamics, and phospholamban (PLB) phosphorylation, regulating Ca2+ pump in enzymatically isolated single guinea pig SANC prior to, during, and following β-adrenoceptor stimulation (isoproterenol) or application of cell-permeant cAMP (CPT-cAMP). Phosphorylation of PLB (Serine 16) was quantified in the same cells following Ca2+ measurement. In dormant SANC LCRs were small and disorganized at baseline, membrane potential was depolarized (−38 ± 1 mV, n = 46), and ICaL, If, and IK densities were smaller vs SANC firing APs. β-adrenoceptor stimulation or application of CPT-cAMP led to de novo spontaneous AP generation in 44 and 46% of dormant SANC, respectively. The initial response was an increase in size, rhythmicity and synchronization of LCRs, paralleled with membrane hyperpolarization and small amplitude APs (rate ∼1 Hz). During the transition to steady-state AP firing, LCR size further increased, while LCR period shortened. LCRs became more synchronized resulting in the growth of an ensemble LCR signal peaked in late diastole, culminating in AP ignition; the rate of diastolic depolarization, AP amplitude, and AP firing rate increased. ICaL, IK, and If amplitudes in dormant SANC increased in response to β-adrenoceptor stimulation. During washout, all changes reversed in order. Total PLB was higher, but the ratio of phosphorylated PLB (Serine 16) to total PLB was lower in dormant SANC. β-adrenoceptor stimulation increased this ratio in AP-firing cells. Thus, transition of dormant SANC to AP firing is linked to the increased functional coupling of membrane and Ca2+ clock proteins. The transition occurs via (i) an increase in cAMP-mediated phosphorylation of PLB accelerating Ca2+ pumping, (ii) increased spatiotemporal LCR synchronization, yielding a larger diastolic LCR ensemble signal resulting in an earlier increase in diastolic INCX; and (iii) increased current densities of If, ICaL, and IK.

The Role of Thalamus Versus Cortex in Epilepsy: Evidence from Human Ictal Centromedian Recordings in Patients Assessed for Deep Brain Stimulation.

The onset of generalized seizures is a long debated subject in epilepsy. The relative roles of cortex and thalamus in initiating and maintaining the different seizure types are unclear. The purpose of the study is to estimate whether the cortex or the centromedian thalamic nucleus is leading in initiating and maintaining seizures in humans. We report human ictal recordings with simultaneous thalamic and cortical electrodes from three patients without anesthesia being assessed for deep brain stimulation (DBS). Patients 1 and 2 had idiopathic generalized epilepsy whereas patient 3 had frontal lobe epilepsy. Visual inspection was combined with nonlinear correlation analysis. In patient 1, seizure onset was bilateral cortical and the belated onset of leading thalamic discharges was associated with an increase in rhythmicity of discharges, both in thalamus and cortex. In patient 2, we observed bilateral independent interictal discharges restricted to the thalamus. However, ictal onset was diffuse, with discharges larger in the cortex even though they were led by the thalamus. In patient 3, seizure onset was largely restricted to frontal structures, with belated lagging thalamic involvement. In human generalized seizures, the thalamus may become involved early or late in the seizure but, once it becomes involved, it leads the cortex. In contrast, in human frontal seizures the thalamus gets involved late in the seizure and, once it becomes involved, it lags behind the cortex. In addition, the centromedian nucleus of the thalamus is capable of autonomous epileptogenesis as suggested by the presence of independent focal unilateral epileptiform discharges restricted to thalamic structures. The thalamus may also be responsible for maintaining the rhythmicity of ictal discharges.

G.P.85 Cerebellar dysfunction in the mdx mouse: An electrophysiological and behavioral study

Patients with Duchenne muscular dystrophy (DMD), besides a severe muscle impairment caused by the absence of dystrophin expression in skeletal muscle, frequently display specific cognitive deficits. These cognitive deficits have been related to the absence of dystrophin in specific regions of the central nervous system, notably cerebellar Purkinje cells (PC). In the central nervous system, dystrophin has recently been involved in GABAA receptors clustering at postsynaptic densities, and its absence, by disrupting this clustering, leads to decreased inhibitory input to PC in mdx mice. Given these abnormalities, we performed an in vivo electrophysiological study of the dystrophin-deficient mdx mouse, to compare cerebellar PC firing behaviour and local field potential (LFP) in alert mdx and control C57Bl/10 mice. We found an altered PC activity in mdx mice, characterized by a significant increase in simple spikes (SS) firing rate, regularity and rhythmicity. Complex spikes (CS) firing rate and duration were not significantly different between mdx and control mice. However, the duration of the pause induced by CS in SS firing was significantly longer in mdx mice. Furthermore, we demonstrated the presence of high frequency (∼160–200Hz) LFP oscillations in the cerebellar cortex of alert mdx mice. Finally, we compared the performance of mdx and control mice in behavioral tests. While the rotarod test revealed no significant difference in performance between mdx and control mice, the catwalk, runway and wire tests demonstrated a moderate impairment of motor coordination and balance in mdx mice. These findings demonstrate the existence of a cerebellar dysfunction in mdx mice. A similar cerebellar dysfunction may be present in patients with DMD and contribute to the cognitive deficits observed in these patients.

Changes in hippocampal cell discharge patterns and theta rhythm spectral properties as a function of walking velocity in the guinea pig.

Dorsal hippocampal theta rhythm (theta) and extracellular unit activity from CA1 pyramidal layer were recorded in awake guinea pigs, both during standing and during walking on a conveyor belt at increasing speeds. Amplitude, frequency and rhythmicity of theta increased linearly with the movement speed. In this preparation we found the same three types of unit discharge patterns that have been described in anesthetized rats in the presence of spontaneous or induced hippocampal theta: type 1, rhythmic at theta frequency and phase-locked with theta; type 2, discharging non-rhythmically but phase-locked with theta; and type 3, discharging at random. Furthermore, all units modified their firing pattern when the animals walked, either by increasing their rhythmicity and/or phase-locking with theta or by increasing their firing frequency. During walking, some type 3 units changed into type 2 or type 1, type 2 units changed to type 1, and type I increased their rhythmicity. Consequently, the unit discharge rhythmicity and phase-locking with theta increased with the speed of movement. The mean rate of neuronal discharges increased linearly as a function of walking speed. In this paper we show that the progressive spectral theta changes determined by the intensity of movement are concomitant with the increase in rhythmicity of hippocampal cells. Moreover, the firing rate of these cells, and the amplitude, frequency and rhythmicity of theta, increased linearly as a function of walking speed, suggesting that neuronal excitation may be basically responsible for these changes in theta properties.

Pew (1966) Revisited: Acquisition of Hierarchical Control as a Function of Observational Practice.

Two experiments are reported that utilized a task similar to one developed by Pew (1966) in which subjects controlled the position of a continually moving cursor by alternately pressing two response keys. Experiments I and 2 replicated Pew's findings. That is, over acquisition trials, subjects exhibited an increase in their rate of responding, an increase in response rhythmicity, and a reduction in error. After a 24-hr retention interval, it was demonstrated that the rate and rhythmicity of responding for the observation practice groups were indistinguishable from those of the actual practice groups. In general, however, as the demands of the task (cursor acceleration rate and/or target amplitude) were increased, there was a tendency for the absolute differences in error between the actual and observation practice groups to increase, These data support the notion that subjects may choose appropriate response/control schemes (i.e., open-loop and hierarchical control) without actual practice experiences.

Observational Learning: Influences on Temporal Response Organization

This article reports the role of actual and observational practice in the learn- ing of a task that required the temporal organization of simple responses. The experiment utilized a task similar to one developed by Pew (1966) in which subjects controlled the position of a continuously moving cursor by alter- nately pressing two response keys. Similar to Pew's findings, our findings demonstrated that, over acquisition trials, subjects exhibited an increase in their rate of responding, an increase in response rhythmicity, and a reduction in position error. More importantly, after a 24-hr retention interval, it was demonstrated that the rate and rhythmicity of responding and error scores for the observation practice group were indistinguishable from those of the actual practice group. These data were consistent with the notion that observation practice was sufficient to organize a response pattern associated with open loop and hierarchical control.

Psychiatric Patients Showing Irregular β Activities in EEGs and Treatment with Antiepileptic Drugs: A Report of 15 Cases†

Fifteen psychiatric cases are reported who were clinically diagnosed as schizophrenic, affective disorders, or neurotic, but resisted standard medication regimens, all showing irregular beta activities on EEGs. The cases tended to display symptoms in common, such as dysphoria, emotional instability or frequent physical complaints. These characteristic symptoms share something mutually with the symptoms shown in some epileptic patients or psychiatric patients with epileptic EEG abnormalities without clinical seizures. Antiepileptic drugs seemed more specifically effective to the above symptoms. More than half of these cases showed improvement on EEG findings such as a decrease in irregular beta activities and an increase in rhythmicity or regularity of alpha activities along with clinical improvement with the administration of adjunctive antiepileptic drugs. These results suggest that the adjunctive administration of antiepileptic drugs to patients with irregular beta activities on EEGs is clinically useful and an EEG examination has much value in psychiatric practice to find the criteria of drug therapy.

Redox regulation of autorhythmic heart contractions and the effect of acetylcholine failed to manifest itself by decreasing [Ca 2+] 0

Earlier it was described by us, that the amplitude and frequency of cyclic autorhythmic contraction of frog heart was decreased by oxidants but increased by reductants. Increasing the redox state potential, acetylcholine effects a positive and not a negative inotropic action. Decreasing the redox state potential, the negative inotropic effect is increased. In search of the site of action of these regulatory influences, the role of [Ca 2+] 0 was investigated recently and it was established, that: 1. 1. Reducing the [Ca 2+] 0 by 50%, an oxidation diminished the amplitude and frequency of cyclic autorhythmic contraction more expressively, than in normal saline. 2. 2. The increase in cyclic rhythmicity caused by reductant failed to manifest itself in Ca 2+ deficient Ringer. 3. 3. The reversing action of oxidation on ACh effects was practically abolished following a decline in [Ca 2+] 0. 4. 4. The effect of reductant to intensify the negative inotropic actions of acetylcholine suffered an inversion. Because both the redox regulation of quantitative and/or qualitative parameters of cyclic autorhythmic contractions and the ACh effect altered significantly and in a non-additive manner, following a decrement in [Ca 2+] 0, it seems to be clear, that as a site of action of redox regulation in normal saline, a change in the involvement of extracellular Ca 2+ (presumably by altering its influx or absorbtive parameters) has to be taken into consideration.

The effects of pentobarbital on rat cerebellar Purkinje cells

1. 1. Cerebellar Purkinje cell unit activity was recorded in urethane anaesthetized rats. 2. 2. Pentobarbital, infused intravenously in three doses of 10 mg/kg or in a single dose of 20 mg/kg, produced an initial increase in complex spike activity with a concomitant decrease in simple spike frequency. 3. 3. There was a subsequent decrease in complex spike activity and an increase in rhythmicity of the simple spike discharge. 4. 4. Pentobarbital also increased the period of Purkinje cell inhibition produced by local surface stimulation.

Application of phase detection and averaging techniques in computer analysis of EEG records in the cat

Consistency of phase patterns in EEG records from the hippocampal system and midbrain reticular formation have been examined in the course of behavioral training in five cats with implated electrodes. These studies have involved novel application of computing techniques, including continuous measurement of phase and amplitude characteristics of single wave trains by digital filtering techniques, the use of cross-spectral analyses with calculation of complex transfer functions, and averaging of records during repeated behavioral performances with calculation of coherence functions in cross-spectral examinations. It was found that rhythmicity appeared in the computed average at the rate of the dominant EEG frequency as T-maze performance reached a high level, and was related to a reduction in scatter in phase patterns at high performance levels. Reversal of behavioral cues was associated with an immediate brief increase in rhythmicity of the average, then a decline followed by a progressive reemergence of rhymicity at the end of retraining. Continuous phase-and-amplitude examinations during delayed response performance indicated a rhythmic phase modulation on wave trains with an apparently single frequency appearing during periods of discrimination. Comparison of probability bounds in cross-spectral analysis with use of a polar coordinate display have indicated major differences in phase relations between different hippocampal regions between correct responses in certain circumstances, with consistency in different examinations. These findings are discussed in relation to a stochastic model of the cerebral system, with reference to the possible role of the wave process in handling and storage of information.