Which bright fast radio bursts repeat?

ABSTRACT A handful of fast radio bursts (FRBs) are now known to repeat. However, the question remains – do they all? We report on an extensive observational campaign with the Australian Square Kilometre Array Pathfinder (ASKAP), Parkes, and Robert C. Byrd Green Bank Telescope, searching for repeat bursts from FRBs detected by the Commensal Real-time ASKAP Fast Transients survey. In 383.2 h of follow-up observations covering 27 FRBs initially detected as single bursts, only two repeat bursts from a single FRB, FRB 171019, were detected, which have been previously reported by Kumar et al. We use simulations of repeating FRBs that allow for clustering in burst arrival times to calculate new estimates for the repetition rate of FRB 171019, finding only slight evidence for incompatibility with the properties of FRB 121102. Our lack of repeat bursts from the remaining FRBs set limits on the model of all bursts being attributable to repeating FRBs. Assuming a reasonable range of repetition behaviour, at most 60 per cent (90 per cent confidence limit) of these FRBs have an intrinsic burst distribution similar to FRB 121102. This result is shown to be robust against different assumptions on the nature of repeating FRB behaviour, and indicates that if indeed all FRBs repeat, the majority must do so very rarely.

Effect of calcium channel blocker as anticonvulsant and its potentiating effect when used along with sodium valproate in pentylenetetrazole induced seizures in Albino rats

Background: Many antiepileptic drugs were introduced for the treatment of epilepsy. Ideal antiepileptic drug should not only prevent but also correct the underlying pathophysiology without altering the normal neurotransmission. Calcium channel blockers may form such group because initiation of seizure is associated intrinsic burst firing which is triggered by large inward calcium current, so this study was done to evaluate the anticonvulsant effect of amlodipine in albino rats.Methods: A total of 42 adult albino rats were included in the study and divided into 7 groups, each containing 6 rats. Group 1 received distilled water, group 2,3 received sodium valproate 50mg/kg and 100mg/kg, group 4-6 received amlodipine 1, 2, 4mg/kg and group 7 received combination of Amlodipine 1 mg/kg and sodium valproate 50mg/kg. Pentylenetetrazole induced seizures model was done and onset of myoclonic jerks, onset of clonic convulsions and duration of clonic convulsions was studied.Results: There was a significant anticonvulsant effect in Amlodipine doses 2, 4mg/kg (p <0.001). The combination of Amlodipine (1mg/kg) and Sodium valproate (50mg/kg) also had significant anticonvulsant effect.Conclusions: Amlodipine, a calcium channel blocker has anticonvulsant effect and also potentiated the anticonvulsant effect of low dose sodium valproate.

T-channels: Short-Term Up-Regulation Causes Long-Term Consequences in Epilepsy

Transcriptional Upregulation of Cav3.2 Mediates Epileptogenesis in the Pilocarpine Model of Epilepsy. Becker AJ, Pitsch J, Sochivko D, Opitz T, Staniek M, Chen CC, Campbell KP, Schoch S, Yaari Y, Beck H. J Neurosci 2008 Dec 3;28(49):13341–13353. In both humans and animals, an insult to the brain can lead, after a variable latent period, to the appearance of spontaneous epileptic seizures that persist for life. The underlying processes, collectively referred to as epileptogenesis, include multiple structural and functional neuronal alterations. We have identified the T-type Ca2+ channel Cav3.2 as a central player in epileptogenesis. We show that a transient and selective upregulation of Cav3.2 subunits on the mRNA and protein levels after status epilepticus causes an increase in cellular T-type Ca2+ currents and a transitional increase in intrinsic burst firing. These functional changes are absent in mice lacking Cav3.2 subunits. Intriguingly, the development of neuropathological hallmarks of chronic epilepsy, such as subfield-specific neuron loss in the hippocampal formation and mossy fiber sprouting, was virtually completely absent in Cav3.2- /– mice. In addition, the appearance of spontaneous seizures was dramatically reduced in these mice. Together, these data establish transcriptional induction of Cav3.2 as a critical step in epileptogenesis and neuronal vulnerability.

Regulation of Burst Dynamics Improves Differential Encoding of Stimulus Frequency by Spike Train Segregation

Distinguishing between different signals conveyed in a single sensory modality presents a significant problem for sensory processing. The weakly electric fish Apteronotus leptorhynchus use electrosensory information to encode both low-frequency signals associated with environmental and prey signals and high-frequency communication signals between conspecifics. We identify a mechanism whereby the GABAB component of a feedback pathway to the electrosensory lobe is recruited to regulate the intrinsic burst dynamics and coding properties of pyramidal cells for these behaviorally relevant input signals. Through recordings in an in vitro slice preparation and a reduced model of pyramidal cells, we show that recruitment of dendritic GABAB currents can shift the timing of a backpropagating spike and its influence on an intrinsic burst mechanism. This regulation of burst firing alters the coding properties of pyramidal cells by improving the correlation of burst and tonic spikes with respect to low- or high-frequency components of complex stimuli. GABAB modulation of spike backpropagation thus improves the segregation of burst and tonic spikes evoked by simulated sensory input, allowing pyramidal cells to parcel the spike train into coding streams for the low- and high-frequency components. As the feedback pathway is predicted to be activated in circumstances where environmental and communication stimuli coexist, these data reveal a novel means by which inhibitory input can regulate spike backpropagation to improve signal segregation.

Lack of correlation between neuronal hyperexcitability and electrocorticographic responsiveness in epileptogenic human neocortex

Object. The purpose of this study was to determine whether intrinsic neuronal properties and synaptic responses differed between interictally active and inactive tissue removed in neocortical resections from patients undergoing surgical treatment for epilepsy.Methods. Whole-cell patch recordings were performed in layer 2 or 3 and layer 5 pyramidal cells in neocortical slices obtained from tissue surgically removed from patients for the treatment of medically intractable seizures. Synaptic responses to stimulation at the layer 6—white matter border were used to classify cells as nonbursting if they responded with only a single action potential for all above-threshold stimuli (80%). These responses were usually followed by biphasic inhibitory postsynaptic potentials (IPSPs). Cells were classified as bursting if they fired at least three action potentials in response to synaptic stimulation (20%). These cells typically showed no IPSPs and responded in either an all-or-nothing or graded fashion. Approximately twice as many cells at layer 2 or 3 (29%) than cells at layer 5 (14%) fired synaptic bursts. Synaptic bursting was not associated with an alteration in a cell's response properties to γ-aminobutyric acid. It was notable that, in tissue samples determined by electrocorticography (ECoG) to be either interictally active or not active, the proportion of cells that burst was exactly the same in both groups (24%). We found no cells with intrinsic burst firing.Conclusions. We conclude that synaptic bursting was characteristic of a small proportion of cells from epileptic tissue; however, this did not correlate with interictal spikes on ECoG.

Role of Intrinsic Burst Firing, Potassium Accumulation, and Electrical Coupling in the Elevated Potassium Model of Hippocampal Epilepsy

Jensen, Morten S. and Yoel Yaari. Role of intrinsic burst firing, potassium accumulation, and electrical coupling in the elevated potassium model of hippocampal epilepsy. J. Neurophysiol. 77: 1224–1233, 1997. Perfusing rat hippocampal slices with high-K+ (7.5 mM) saline induced brief population bursts originating in CA3 at 0.5–1 Hz and spreading synaptically into CA1. In 42% of the slices the brief bursts evoked in CA1 gave way every 0.5–2 s to sustained ictal (or seizure) episodes with tonic and clonic components. Paired intra- and extracellular recordings in the CA1 pyramidal layer were used to characterize the synaptic and nonsynaptic mechanisms generating the brief and sustained epileptiform events. The interictal, tonic, or clonic primary burst response in CA1 comprised a spindle-shaped, tight cluster (170–180 Hz) of five to seven population spikes. Bursts evoked between sequential seizures (interictal bursts) were initially small and progressively increased in size. Concurrently, basal extracellular K+ concentration ([K+]o) increased from 6.5 to 7.5 mM. The tonic event emanated from a large primary burst and comprised prolonged (>1 s), self-sustained afterdischarge, associated with a rise in [K+]o to 12 mM. Bursts generated during the subsequent [K+]o decline (clonic bursts) also were large and followed by some afterdischarge. They became small during [K+]o undershoot to 6.5 mM. Intrinsically burst firing pyramidal cells (PCs) were recruited before or at the very onset of the primary population burst and fired repetitively during its course. Nonbursters were recruited ≥10 ms after the beginning of the primary burst and fired, on average, only one spike. The PCs depolarized during the primary burst and subsequent afterdischarge. The primary depolarizing shift was larger in bursters than in nonbursters. Both bursters and nonbursters fired repetitively, albeit intermittently, during tonic and clonic afterdischarge. Throughout the interictal-ictal cycle intracellular spikes were time-locked to population spikes, indicating that PCs fire in tight synchrony. Differential recording of transmembrane potentials unmasked rapid (4–7 ms) transmembrane depolarizing potentials of up to 10 mV, coincident with population spikes. We conclude that in the high-K+ model of hippocampal epilepsy, the local generation of population bursts in CA1 is led by intrinsic bursters, which recruit and synchronize other PCs by synaptic, electrical, and K+-mediated excitatory interactions. The cycling between interictal, tonic, and clonic events appears to result from feedback interactions between neuronal discharge and [K+]o.