scholarly journals KCNQ/Kv7 Channel Regulation of Hippocampal Gamma-Frequency Firing in the Absence of Synaptic Transmission

2006 ◽  
Vol 95 (5) ◽  
pp. 3105-3112 ◽  
Author(s):  
S. Piccinin ◽  
A. D. Randall ◽  
J. T. Brown
Keyword(s):  
Synaptic Transmission ◽  
High Frequency ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Neuronal Firing ◽  
Population Spike ◽  
Channel Blockers ◽  
Kv7 Channels ◽  
Population Spikes ◽  
Gamma Frequency

Synchronous neuronal firing can be induced in hippocampal slices in the absence of synaptic transmission by lowering extracellular Ca2+ and raising extracellular K+. However, the ionic mechanisms underlying this nonsynaptic synchronous firing are not well understood. In this study we have investigated the role of KCNQ /Kv7 channels in regulating this form of nonsynaptic bursting activity. Incubation of rat hippocampal slices in reduced (<0.2 mM) [Ca2+]o and increased (6.3 mM) [K+]o, blocked synaptic transmission, increased neuronal firing, and led to the development of spontaneous periodic nonsynaptic epileptiform activity. This activity was recorded extracellularly as large (4.7 ± 1.9 mV) depolarizing envelopes with superimposed high-frequency synchronous population spikes. These intraburst population spikes initially occurred at a high frequency (about 120 Hz), which decayed throughout the burst stabilizing in the gamma-frequency band (30–80 Hz). Further increasing [K+]o resulted in an increase in the interburst frequency without altering the intraburst population spike frequency. Application of retigabine (10 μM), a Kv7 channel modulator, completely abolished the bursts, in an XE-991–sensitive manner. Furthermore, application of the Kv7 channel blockers, linopirdine (10 μM) or XE-991 (10 μM) alone, abolished the gamma frequency, but not the higher-frequency population spike firing observed during low Ca2+/high K+ bursts. These data suggest that Kv7 channels are likely to play a role in the regulation of synchronous population firing activity.

scholarly journals Hyperoxic stimulation of synchronous orthodromic activity and induction of neural plasticity does not require changes in excitatory synaptic transmission

2010 ◽  
Vol 109 (3) ◽  
pp. 820-829 ◽  
Author(s):  
Alfredo J. Garcia ◽  
Robert W. Putnam ◽  
Jay B. Dean
Keyword(s):  
Synaptic Transmission ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Excitatory Synaptic Transmission ◽  
Population Spike ◽  
Excitatory Postsynaptic Potential ◽  
Synaptic Activation ◽  
Ca1 Neurons ◽  
Stimulation Of

The first study, described in the companion article, reports that acute exposure of rat hippocampal slices to either hyperbaric oxygen (HBO: 2.84 and 4.54 atmospheres absolute, ATA) or normobaric reoxygenation (NBOreox; i.e., normobaric hyperoxia: 0.6 or 0.0 → 0.95 ATA) stimulates synchronous orthodromic activity in CA1 neurons, which includes activation of O2-induced potentiation (OxIP) and, in some cases, hyperexcitability (secondary population spikes, sPS). In this second study we tested the hypothesis that HBO and NBOreox increase orthodromic activity of CA1 neurons (oPS, orthodromic population spike) and OxIP via a combination of both increased excitatory synaptic transmission (field excitatory postsynaptic potential, fEPSP) and intrinsic excitability (antidromic population spike, aPS). HBO and NBOreox increased the oPS but rarely increased or potentiated the fEPSP. HBO exposure produced epileptiform antidromic activity, which was abolished during inhibition of fast GABAergic and glutamatergic synaptic transmission. Decreasing O2 from 0.95 ATA (control) to 0.6 ATA (intermediate O2) or 0.0 ATA (hypoxia) reversibly abolished the fEPSP, and reoxygenation rarely induced potentiation of the fEPSP or aPS. Intracellular recordings and antidromic field potential recordings, however, revealed that synaptic transmission and neuronal excitability were preserved, albeit at lower levels, in 0.60 ATA O2. Together, these data indicate that 1) the changes in excitatory postsynaptic activity are not required for stimulation of the oPS during and HBO/NBOreox or for activation of OxIP, suggesting the latter is a form of intrinsic plasticity; 2) HBO disinhibits spontaneous synaptic transmission to induce epileptiform activity; and 3) although synchronous synaptic activation of the CA1 neuronal population requires hyperoxia (i.e., 0.95 ATA O2), synaptic activation of individual CA1 neurons does not.

Enhanced NMDAR-dependent epileptiform activity is controlled by oxidizing agents in a chronic model of temporal lobe epilepsy

1996 ◽  
Vol 76 (6) ◽  
pp. 4185-4189 ◽  
Author(s):  
J. C. Hirsch ◽  
O. Quesada ◽  
M. Esclapez ◽  
H. Gozlan ◽  
Y. Ben-Ari ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Ex Vivo ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Nmda Antagonist ◽  
Pyramidal Cells ◽  
Resting Membrane Potential ◽  
Postsynaptic Potentials ◽  
Epileptiform Discharges ◽  
Late Part

1. Graded N-methyl-D-aspartate receptor (NMDAR)-dependent epileptiform discharges were recorded from ex vivo hippocampal slices obtained from rats injected a week earlier with an intracerebroventricular dose of kainic acid. Intracellular recordings from pyramidal cells of the CA1 area showed that glutamate NMDAR actively participated in synaptic transmission, even at resting membrane potential. When NMDAR were pharmacologically isolated, graded burst discharges could still be evoked. 2. The oxidizing reagent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB, 200 microM, 15 min) suppressed the late part of the epileptiform burst that did not recover after wash but could be reinstated by the reducing agent tris (2-carboxyethyl) phosphine (TCEP, 200 microM, 15 min) and again abolished with the NMDA antagonist D-2-amino-5-phosphonovaleric acid (D-APV). 3. Pharmacologically isolated NMDAR-mediated responses were decreased by DTNB (56 +/- 10%, mean +/- SD, n = 6), an effect reversed by TCEP. 4. When only the fast glutamateric synaptic component was blocked, NMDA-dependent excitatory postsynaptic potentials (EPSPs) could be evoked despite the presence of underlying fast and slow inhibitory postsynaptic potentials (IPSPs). DTNB decreased EPSPs to 48 +/- 12% (n = 5) of control. 5. Since a decrease of the NMDAR-mediated response by +/- 50% is sufficient to suppress the late part of the burst, we suggest that epileptiform activity can be controlled by manipulation of the redox sites of NMDAR. Our observations raise the possibility of developing new anticonvulsant drugs that would spare alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-R (AMPAR)-mediated synaptic responses and decrease NMDAR-mediated synaptic transmission without blocking it completely.

Heptanol But Not Fluoroacetate Prevents the Propagation of Spreading Depression in Rat Hippocampal Slices

1997 ◽  
Vol 77 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Carlota Largo ◽  
Geoffrey C. Tombaugh ◽  
Peter G. Aitken ◽  
Oscar Herreras ◽  
George G. Somjen
Keyword(s):  
Synaptic Transmission ◽  
Gap Junctions ◽  
Spreading Depression ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Lipid Phase ◽  
Tissue Slices ◽  
Population Spikes ◽  
Afferent Volleys ◽  
Stimulation Of

Largo, Carlota, Geoffrey C. Tombaugh, Peter G. Aitken, Oscar Herreras, and George G. Somjen. Heptanol but not fluoroacetate prevents the propagation of spreading depression in rat hippocampal slices. J. Neurophysiol. 77: 9–16, 1997. We investigated whether heptanol and other long-chain alcohols that are known to block gap junctions interfere with the generation or the propagation of spreading depression (SD). Waves of SD were triggered by micro-injection of concentrated KCl solution in stratum (s.) radiatum of CA1 of rat hippocampal tissue slices. DC-coupled recordings of extracellular potential ( V o) were made at the injection and at a second site ∼1 mm distant in st. radiatum and sometimes also in st. pyramidale. Extracellular excitatory postsynaptic potentials (fEPSPs) were evoked by stimulation of the Schaffer collateral bundle; in some experiments, antidromic population spikes were evoked by stimulation of the alveus. Bath application of 3 mM heptanol or 5 mM hexanol completely and reversibly prevented the propagation of the SD-related potential shift (Δ V o) without abolishing the Δ V o at the injection site. Octanol (1 mM) had a similar but less reliably reversible effect. fEPSPs were depressed by ∼30% by heptanol and octanol, 65% by hexanol. Antidromic population spikes were depressed by 30%. In isolated, patch-clamped CA1 pyramidal neurons, heptanol partially and reversibly depressed voltage-dependent Na currents possibly explaining the slight depression of antidromic spikes and, by acting on presynaptic action potentials, also the depression of fEPSPs. Fluoroacetate (FAc), a putative selective blocker of glial metabolism, first induced multiple spike firing in response to single afferent volleys and then severely suppressed synaptic transmission (confirming earlier reports) without depressing the antidromic population spike. FAc did not inhibit SD propagation. The effect of alkyl alcohols is compatible with the idea that the opening of normally closed neuronal gap junctions is required for SD propagation. Alternative possible explanations include interference with the lipid phase of neuron membranes. The absence of SD inhibition by FAc confirms that synaptic transmission is not necessary for the propagation of SD, and it suggests that normally functioning glial cells are not essential for SD generation or propagation.

scholarly journals NMDA Receptor Activation Mediates Hydrogen Peroxide–Induced Pathophysiology in Rat Hippocampal Slices

2002 ◽  
Vol 87 (6) ◽  
pp. 2896-2903 ◽  
Author(s):  
Marat V. Avshalumov ◽  
Margaret E. Rice
Keyword(s):  
Nmda Receptor ◽  
Oxidative Damage ◽  
Synaptic Transmission ◽  
Glutamate Uptake ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Ros Generation ◽  
Progressive Degeneration

Endogenous reactive oxygen species (ROS) can act as modulators of neuronal activity, including synaptic transmission. Inherent in this process, however, is the potential for oxidative damage if the balance between ROS production and regulation becomes disrupted. Here we report that inhibition of synaptic transmission in rat hippocampal slices by H2O2 can be followed by electrical hyperexcitability when transmission returns during H2O2 washout. As in previous studies, H2O2exposure (15 min) reversibly depressed the extracellular population spike (PS) evoked by Schaffer collateral stimulation. Recovery of PS amplitude, however, was typically accompanied by mild epileptiform activity. Inclusion of ascorbate (400 μM) during H2O2 washout prevented this pathophysiology. No protection was seen with isoascorbate, which is a poor substrate for the stereoselective ascorbate transporter and thus remains primarily extracellular. Epileptiform activity was also prevented by the N-methyl-d-aspartate (NMDA) receptor antagonist, dl-2-amino-5-phosphonopentanoic acid (AP5) during H2O2washout. Once hyperexcitability was induced, however, AP5 did not reverse it. When present during H2O2 exposure, AP5 did not alter PS depression by H2O2but did inhibit the recovery of PS amplitude seen during pulse-train stimulation (10 Hz, 5 s) in H2O2. Inhibition of glutamate uptake by l- trans-2,4-pyrrolidine dicarboxylate (PDC; 50 μM) during H2O2washout markedly enhanced epileptiform activity; coapplication of ascorbate with PDC prevented this. These data indicate that H2O2 exposure can cause activation of normally silent NMDA receptors, possibly via inhibition of redox-sensitive glutamate uptake. When synaptic transmission returns during H2O2 washout, enhanced NMDA receptor activity leads to ROS generation and consequent oxidative damage. These data reveal a pathological cycle that could contribute to progressive degeneration in neurological disorders that involve oxidative stress, including cerebral ischemia.

scholarly journals Suppression of epileptiform activity by high frequency sinusoidal fields in rat hippocampal slices

2001 ◽  
Vol 531 (1) ◽  
pp. 181-191 ◽  
Author(s):  
Marom Bikson ◽  
Jun Lian ◽  
Philip J. Hahn ◽  
William C. Stacey ◽  
Christopher Sciortino ◽  
...  
Keyword(s):  
High Frequency ◽  
Epileptiform Activity ◽  
Hippocampal Slices

scholarly journals Signaling Mechanisms Mediating BDNF Modulation of Synaptic Plasticity in the Hippocampus

1999 ◽  
Vol 6 (3) ◽  
pp. 243-256 ◽  
Author(s):  
Wolfram A. Gottschalk ◽  
Hao Jiang ◽  
Nicole Tartaglia ◽  
Linyin Feng ◽  
Alexander Figurov ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Neurotrophic Factor ◽  
High Frequency ◽  
Hippocampal Slices ◽  
Close Relative ◽  
Signaling Mechanisms ◽  
Neurotrophin 3 ◽  
Neurotrophin Signaling

Although recent studies indicate that brain-derived neurotrophic factor (BDNF) plays an important role in hippocampal synaptic plasticity, the underlying signaling mechanisms remain largely unknown. Here, we have characterized the signaling events that mediate the BDNF modulation of high-frequency synaptic transmission. Mitogen-associated protein kinase (MAPK), phosphotidylinositol-3 kinase (PI3K), and phospholipase C-γ (PLC-γ) are the three signaling pathways known to mediate neurotrophin signaling in other systems. In neonatal hippocampal slices, application of BDNF rapidly activated MAPK and PI3K but not PLC-γ. BDNF greatly attenuated synaptic fatigue at CA1 synapses induced by a train of high-frequency, tetanic stimulation (HFS). Inhibition of the MAPK and PI3K, but not PLC-γ, prevented the BDNF modulation of high-frequency synaptic transmission. Neurotrophin-3 (NT-3), a close relative of BDNF, did not activate MAPK or PI3K and had no effect on synaptic fatigue in the neonatal hippocampus. Neither forskolin, which activated MAPK but not PI3 kinase, nor ciliary neurotrophic factor (CNTF), which activated PI3K but not MAPK, affected HFS-induced synaptic fatigue. Treatment of the slices with forskolin together with CNTF still had no effect on synaptic fatigue. Thus, although the activation of MAPK and PI3K is required, the two together are not sufficient to mediate the BDNF effect. Inhibition of new protein synthesis by anisomycin or cycloheximide did not prevent the BDNF effect. These data suggest that BDNF modulation of high-frequency transmission is independent of protein synthesis but requires MAPK and PI3K and yet another signaling pathway to act together in the hippocampus.

Spread of synchronous firing in longitudinal slices from the CA3 region of the hippocampus

1988 ◽  
Vol 60 (4) ◽  
pp. 1481-1496 ◽  
Author(s):  
R. Miles ◽  
R. D. Traub ◽  
R. K. Wong
Keyword(s):  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Neuronal Firing ◽  
Burst Firing ◽  
Stratum Radiatum ◽  
Synaptic Inhibition ◽  
Firing Threshold ◽  
Single Action ◽  
Synchronous Firing ◽  
Ca3 Region

1. Mechanisms underlying the propagation of synchronous epileptiform activity in disinhibited hippocampal slices were examined in experimental and computer simulation studies. 2. Experiments were performed with longitudinal slices of the CA3 region. Synchronous firing was initiated by stimulating stratum radiatum fibers in the presence of picrotoxin. It propagated smoothly and without decrement at velocities close to 0.15 m/s over distances up to 10 mm. 3. In elevated extracellular calcium, neuronal firing threshold was increased and synchronous burst firing did not spread. Monophasic excitatory postsynaptic potentials (EPSPs) were recorded in cells at limited distances from a stimulus in the presence of 10 mM Ca and picrotoxin. Axonal conduction velocity, estimated from EPSP latencies, was several times faster than the spread of synchronous firing. 4. EPSPs recorded in 5-7 mM Ca and picrotoxin could consist of two components. The properties of the first component were similar to those of synaptic events recorded in 10 mM Ca. The second component was of longer latency and unlike the first component was suppressed in responses to paired stimuli at interval 50-300 ms. Recordings from cells at different distances from a stimulus suggested that the second component spread further and more slowly than the first component. 5. In computer simulations the CA3 region was represented by a spatially distributed network of 9,000 excitatory neurons and 900 inhibitory cells. Individual cells and synapses had properties based on experimental data. The effects of varying synaptic strength and connectivity on the spread of activity in the model was examined. 6. When synaptic inhibition was functional in simulations, firing was restricted to a single action potential in model cells close to the stimulus, as in experiments. Synchronous burst firing spread throughout the neuronal array when fast synaptic inhibition was absent. The velocity of propagation was slower than conduction in simulated axons when synaptic contacts made by excitatory cells were spatially limited. Propagation velocity increased with increases in the spatial extent of excitatory connectivity. 7. Increasing the threshold of neurons in a region of the model network reduced the speed at which synchronous firing spread. In experiments focal application of gamma-aminobutyric acid (GABA) elevated neuronal firing threshold and slowed the propagation of synchrony in a local region. 8. As the strength of synaptic inhibition was gradually reduced, neuronal activity spread further and faster through the simulated neuronal network.(ABSTRACT TRUNCATED AT 400 WORDS)

Etomidate Does Not Alter Recovery after Anoxia of Evoked Population Spikes Recorded from the CA1 Region of Rat Hippocampal Slices 

1998 ◽  
Vol 88 (5) ◽  
pp. 1274-1280 ◽  
Author(s):  
Eduarda M. Amadeu ◽  
Elisabeth A. Abramowicz ◽  
Geoffrey Chambers ◽  
James E. Cottrell ◽  
Ira S. Kass
Keyword(s):  
Propylene Glycol ◽  
Adenosine Triphosphate ◽  
Hippocampal Slices ◽  
Population Spike ◽  
High Concentration ◽  
Population Spikes ◽  
Ca1 Region ◽  
Cardiovascular Depression ◽  
Collateral Pathway

Background Etomidate is an anesthetic agent that reduces the cerebral metabolic rate and causes minimal cardiovascular depression. Its ability to improve recovery after anoxia or ischemia is equivocal. An in vitro neuronal preparation was used to examine the action of etomidate on electrophysiologic and biochemical parameters during and after anoxia. Methods The Schaffer collateral pathway was stimulated, and a postsynaptic evoked population spike was recorded from the CA1 pyramidal cell layer of rat hippocampal slices. Etomidate or propylene glycol, its solvent, was present 15 min before, during, and 10 min after anoxia. Adenosine triphosphate, sodium, and potassium concentrations were measured at the end of anoxia in tissue treated with etomidate, propylene glycol, or with no added drugs. Results Etomidate did not alter recovery after 6 min of anoxia. The population spikes from untreated slices recovered to 32% of their preanoxic amplitude, and slices treated with 0.5, 3, and 30 microg/ml etomidate recovered to 24%, 35%, and 13%, respectively. Slices treated with propylene glycol, equivalent to that in 3 and 30 microg/ml etomidate, recovered to 46% and 12%, respectively, and this was not significantly different from untreated slices. Etomidate did not attenuate the decrease in adenosine triphosphate concentrations during anoxia. The increase in sodium and the decrease in potassium during anoxia were significantly attenuated by 30 but not by 3 microg/ml etomidate. Conclusions A range of etomidate concentrations did not significantly alter recovery of the evoked population spike after anoxia in rat hippocampal slices. A high concentration of etomidate did attenuate the increase in sodium and the decrease in potassium during anoxia.

scholarly journals Acute Intrahippocampal Infusion of BDNF Induces Lasting Potentiation of Synaptic Transmission in the Rat Dentate Gyrus

1998 ◽  
Vol 79 (1) ◽  
pp. 496-499 ◽  
Author(s):  
Elhoucine Messaoudi ◽  
Kjetil Bårdsen ◽  
Bolek Srebro ◽  
Clive R. Bramham
Keyword(s):  
Synaptic Transmission ◽  
Dentate Gyrus ◽  
Granule Cells ◽  
Molecular Layer ◽  
Epileptiform Activity ◽  
Population Spike ◽  
Perforant Path ◽  
Excitatory Postsynaptic Potential ◽  
Adult Rats ◽  
Fepsp Slope

Messaoudi, Elhoucine, Kjetil Bårdsen, Bolek Srebro, and Clive R. Bramham. Acute intrahippocampal infusion of BDNF induces lasting potentiation of synaptic transmission in the rat dentategyrus. J. Neurophysiol. 79: 496–499, 1998. The effect of acuteintrahippocampal infusion of brain-derived neurotrophic factor (BDNF) on synaptic transmission in the dentate gyrus was investigated in urethan-anesthetized rats. Medial perforant path-evoked field potentials were recorded in the dentate hilus and BDNF-containing buffer was infused (4 μl, 25 min) immediately above the dentate molecular layer. BDNF led to a slowly developing increase of the field excitatory postsynaptic potential (fEPSP) slope and population spike amplitude. The potentiation either reached a plateau level at ∼2 h after BDNF infusion or continued to increase for the duration of experiment; the longest time point recorded was 10 h. Mean increases at 4 h after BDNF infusion were 62.2 and 224% for the fEPSP slope and population spike, respectively. No changes in responses were observed in controls receiving buffer medium only or buffer containing cytochrome C. BDNF-induced potentiation developed in the absence of epileptiform activity in the hippocampal electroencephalogram or changes in recurrent inhibition on granule cells as assessed by paired-pulse inhibition of the population spike. We conclude that exogenous BDNF induces a lasting potentiation of synaptic efficacy in the dentate gyrus of anesthetized adult rats.

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