1,721,084 research outputs found
Repetitive low-frequency stimulation reduces epileptiform synchronization in limbic neuronal networks.
Full text linkDeep-brain electrical or transcranial magnetic stimulation may represent a therapeutic tool for controlling seizures in patients presenting with epileptic disorders resistant to antiepileptic drugs. In keeping with this clinical evidence, we have reported that repetitive electrical stimuli delivered at approximately 1 Hz in mouse hippocampus-entorhinal cortex (EC) slices depress the EC ability to generate ictal activity induced by the application of 4-aminopyridine (4AP) or Mg2+-free medium (Barbarosie, M., Avoli, M., 1997. CA3-driven hippocampal–entorhinal loop controls rather than sustains in vitro limbic seizures. J. Neurosci. 17, 9308–9314.). Here, we confirmed a similar control mechanism in rat brain slices analyzed with field potential recordings during 4AP (50 μM) treatment. In addition, we used intrinsic optical signal (IOS) recordings to quantify the intensity and spatial characteristics of this inhibitory influence. IOSs reflect the changes in light transmittance throughout the entire extent of the slice, and are thus reliable markers of limbic network epileptiform synchronization. First, we found that in the presence of 4AP, the IOS increases, induced by a train of electrical stimuli (10 Hz for 1 s) or by recurrent, single-shock stimulation delivered at 0.05 Hz in the deep EC layers, are reduced in intensity and area size by low-frequency (1 Hz), repetitive stimulation of the subiculum; these effects were observed in all limbic areas contained in the slice. Second, by testing the effects induced by repetitive subicular stimulation at 0.2–10 Hz, we identified maximal efficacy when repetitive stimuli are delivered at 1 Hz. Finally, we discovered that similar, but slightly less pronounced, inhibitory effects occur when repetitive stimuli at 1 Hz are delivered in the EC, suggesting that the reduction of IOSs seen during repetitive stimulation is pathway dependent as well as activity dependent. Thus, the activation of limbic networks at low frequency reduces the intensity and spatial extent of the IOS changes that accompany ictal synchronization in an in vitro slice preparation. This conclusion supports the view that repetitive stimulation may represent a potential therapeutic tool for controlling seizures in patients with pharmacoresistant epileptic disorders
Calcium-activated potassium channels recorded from rat neocortical neurons in cell culture
No full textRat neocortical neurons in cell culture were studied with the patch-clamp technique in order to determine the properties of a large-conductance K+ channel in excised inside-out patches. In the presence of a physiological ionic gradient for K+ across the patch membrane ([K+]i = 120 mM; [K+]o = 3 mM), outward channel activity was detected when the patches were brought to membrane potential values less negative than -30 mV. Depolarization of the membrane increased the magnitude of the current. The I-V relationship displayed rectification at negative membrane potentials. When the I-V curve was differentiated the slope conductance calculated at 0 mV membrane potential was 120 pS. The single-channel permeability was 5.2 x 10(-13) cm/s and the current flow through the open K+ channel could be modeled using the constant-field electrodiffusion theory. K+ channel opening was not observed following removal of Ca2+ from the intracellular surface of the membrane. Our experiments indicate that, as in other cell types, rat neocortical neurons in culture exhibit a large-conductance K+ channel which is activated by Ca2+ acting on the cytoplasmic surface
Effects induced by the antiepileptic drug valproic acid upon the ionic currents recorded in rat neocortical neurons in cell culture
No full textRat neocortical neurons in culture were subjected to the whole cell mode of voltage clamping under experimental conditions designed to study Na+, Ca2+ and K+ currents in isolation. Following pharmacological blockade of most of the Ca2+ and K+ channels, depolarizing commands which brought the membrane potential from -80 to +10 mV elicited an inward current. This current was sensitive to tetrodotoxin (TTX) and was therefore caused by the opening of voltage-dependent channels permeable to Na+. Extracellular application of the antiepileptic drug valproic acid (VPA, 0.2-2mM) reduced in a dose-related, reversible way this Na+ current. VPA also evoked an increase of the voltage-dependent inward current recorded in the presence of TTX and thus presumably carried by Ca2+; this effect was seen in the presence of doses of VPA larger than 0.5 mM and was not reversible. Two types of outward K+ currents evoked by depolarizing steps in the presence of Na+ and Ca2+ channels blockers were not affected by VPA (up to 5 mM). Our data indicate that doses of VPA that are within the range present when it is used as an anticonvulsant, can influence inward currents generated by rat neocortical cells in culture. The reduction of the Na+, inward current is in line with findings obtained in mouse neurons by using standard intracellular recording techniques. This effect might represent an important mechanism of action for VPA in neocortex
Lamotrigine reduces voltage-gated sodium currents in rat central neurons in culture
No full textTo study the mechanism or mechanisms of action of lamotrigine (LTG) and, in particular, to establish its effects on the function of NA+ channels in mammalian central neurons
Control of spontaneous epileptiform discharges by extracellular potassium: an "in vitro" study in the CA1 subfield of the hippocampal slice
No full text1. The effects evoked by changing [K+]o upon the synchronous epileptiform discharges (SEDs) generated in the presence of GABA antagonists were studied in the "in vitro" hippocampal slice with extra- and intracellular recordings. [K+] in the artificial cerebrospinal fluid (ACSF) was varied in steps of 1 or 2 mM between 3.25 and 10.25 mM. 2. Spontaneous SEDs occurred rarely at [K+]o lower than 5.25 mM. Augmenting [K+]o from 5.25 to 10.25 mM caused a four to five fold increase in the frequency of occurrence of SEDs while the duration of each SED was inversely related to the rate of occurrence. 3. Similar findings were observed when the CA1 subfield had been surgically disconnected from the CA2-CA3 subfields. In these experiments SEDs occurred independently in the two regions, but at any given [K+]o SEDs in the CA3 subfield displayed a frequency two to three times higher than that of SEDs generated in the CA1 area. 4. The intracellular correlate of the SEDs in the CA1 subfield either intact or isolated from the CA2-CA3 ones was a large amplitude depolarization (duration 100-600 ms) associated with a burst of action potentials. This intracellular event, which was similar to the paroxysmal depolarizing shift (PDS) recorded in focal models of epilepsy "in vivo", behaved largely like a synaptic phenomenon when the resting membrane potential (Vm) was changed with intracellularly injected current. A long lasting (half-width: 0.3-2 s in 6.25 mM [K+]o) hyperpolarizing potential usually followed the PDS and could be inverted by hyperpolarizing the Vm by 15-25 mV. When [K+] in the ACSF was raised from 7.25 to 10.25 mM, pyramidal cells depolarized in a dose related fashion. At the same time the post-PDS hyperpolarization decreased in duration and peaked earlier, thus curtailing the depolarizing envelope of the PDS. Consequently, the effect of increasing [K+]o was that of evoking more frequent, but shorter PDSs. 6. These findings demonstrate that the appearance of spontaneous SEDs in the presence of GABA antagonists is dependent upon [K+]o. The effects of evoked by increasing [K+]o are presumably mediated through: (i) a decreased strength of K+ repolarizing conductances; (ii) an increased efficacy of synaptic potentials; (iii) a steady depolarization of the neuronal membrane. The modulation of the frequency of occurrence of SEDs appears to be related to a decreased duration of the hyperpolarization which follows the PDS, a potential which is largely mediated by a K+ conductance
High-frequency oscillations and focal seizures in epileptic rodents
No full textHigh-pass filtering (> 80 Hz) of EEG signals has enabled neuroscientists to analyze high-frequency oscillations (HFOs; i.e., ripples: 80–200 Hz and fast ripples: 250–500 Hz) in epileptic patients presenting with focal seizures and in animal models mimicking this condition. Evidence obtained from these studies indicate that HFOs mirror pathological network activity that may initiate and sustain ictogenesis and epileptogenesis. HFOs are observed in temporal lobe regions of epileptic animals during interictal periods but they also occur before seizure onset and during the ictal period, suggesting that they can pinpoint to the mechanisms of seizure generation. Accordingly, ripples and fast ripples predominate during two specific seizure onset patterns termed low-voltage fast and hypersynchronous, respectively. In this review we will: (i) summarize these experimental studies; (ii) consider the evolution of HFOs over time during epileptogenesis; (iii) address data obtained with optogenetic stimulating procedures both in vitro and in vivo, and (iv) take into account the impact of anti-epileptic drugs on HFOs. We expect these findings to contribute to understanding the neuronal mechanisms leading to ictogenesis and epileptogenesis thus leading to the development of mechanistically targeted anti-epileptic strategies
Topiramate decreases epileptiform synchronization in the rat combined hippocampus-entorhinal cortex slice
No full textFailure of the antiepileptic drug valproic acid to modify synaptic and non-synaptic responses of CA1 hippocampal pyramidal cells maintained 'in vitro'
No full textThe mechanisms of action of the antiepileptic drug valproic acid (VPA) were analyzed in 24 CA1 pyramidal neurons of the 'in vitro' hippocampal slice by using standard intracellular recording techniques. VPA (0.5-2 mM) failed to induce any significant change in the amplitude of the orthodromic EPSPs and the amplitude and duration of the IPSPs evoked by orthodromic or antidromic stimuli. The repetitive firing induced by depolarizing current pulses and the subsequent long lasting afterhyperpolarization were also not affected by VPA. We conclude that VPA, at doses within the therapeutic range, does not potentiate GABA-mediated inhibition in this preparation and probably acts on mechanisms which are not operating or fully expressed in normal (i.e., non-epileptic) situations
Effects of some biogenic amines on spontaneous and evoked electrocortical activity in rats
No full textNeuronal network synchronization and limbic seizures
No full textP>Seizure discharges involving hippocampus and parahippocampal structures are the hallmark of temporal lobe epilepsy (TLE). Herein we discuss neuronal synchronization in limbic networks from control and epileptic brains under conditions that are inductive for the generation of seizure-like discharges. In particular, we address the paradoxic role played by inhibitory mechanisms in supporting epileptiform hypersynchrony. For an expanded treatment of this topic see Jasper's Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books)
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