Permanent Reduction of Seizure Threshold in Post-Ischemic CA3 Pyramidal Neurons

2000 ◽  
Vol 83 (4) ◽  
pp. 2040-2046 ◽  
Author(s):  
Patrice Congar ◽  
Jean-Luc Gaïarsa ◽  
Théodora Popovici ◽  
Yezekiel Ben-Ari ◽  
Valérie Crépel
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Seizure Threshold ◽  
Resting Membrane Potential ◽  
Epileptic Syndromes ◽  
Ca3 Pyramidal Neurons ◽  
Ca3 Pyramidal Cells ◽  
Firing Properties

The effects of ischemia were examined on CA3 pyramidal neurons recorded in hippocampal slices 2–4 mo after a global forebrain insult. With intracellular recordings, CA3 post-ischemic neurons had a more depolarized resting membrane potential but no change of the input resistance, spike threshold and amplitude, fast and slow afterhyperpolarization (AHP) or ADP, and firing properties in response to depolarizing pulses. With both field and whole-cell recordings, synaptic responses were similar in control and post-ischemic neurons. Although there were no spontaneous network-driven discharges, the post-ischemic synaptic network had a smaller threshold to generate evoked and spontaneous synchronized burst discharges. Thus lower concentrations of convulsive agents (kainate, high K+) triggered all-or-none network-driven synaptic events in post-ischemic neurons more readily than in control ones. Also, paired-pulse protocol generates, in post-ischemics but not controls, synchronized field burst discharges when interpulse intervals ranged from 60 to 100 ms. In conclusion, 2–4 mo after the insult, the post-ischemic CA3 pyramidal cells are permanently depolarized and have a reduced threshold to generate synchronized bursts. This may explain some neuropathological and behavioral consequences of ischemia as epileptic syndromes observed several months to several years after the ischemic insult.

Membrane Potential of CA3 Hippocampal Pyramidal Cells During Postnatal Development

2003 ◽  
Vol 90 (5) ◽  
pp. 2964-2972 ◽  
Author(s):  
Roman Tyzio ◽  
Anton Ivanov ◽  
Cristophe Bernard ◽  
Gregory L. Holmes ◽  
Yehezkiel Ben-Ari ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Postnatal Development ◽  
Developmental Change ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Whole Cell ◽  
Perforated Patch ◽  
Ca3 Pyramidal Cells ◽  
Whole Cell Recordings

A depolarized resting membrane potential has long been considered to be a universal feature of immature neurons. Despite the physiological importance, the underlying mechanisms of this developmental phenomenon are poorly understood. Using perforated-patch, whole cell, and cell-attached recordings, we measured the membrane potential in CA3 pyramidal cells in hippocampal slices from postnatal rats. With gramicidin perforated-patch recordings, membrane potential was –44 ± 4 (SE) mV at postnatal days P0–P2, and it progressively shifted to –67 ± 2 mV at P13–15. A similar developmental change of the membrane potential has been also observed with conventional whole cell recordings. However, the value of the membrane potential deduced from the reversal potential of N-methyl-d-aspartate channels in cell-attached recordings did not change with age and was –77 ± 2 mV at P2 and –77 ± 2 mV at P13–14. The membrane potential measured using whole cell recordings correlated with seal and input resistance, being most depolarized in neurons with high, several gigaohms, input resistance and low seal resistance. Simulations revealed that depolarized values of the membrane potential in whole cell and perforated-patch recordings could be explained by a shunt through the seal contact between the pipette and membrane. Thus the membrane potential of CA3 pyramidal cells appears to be strongly negative at birth and does not change during postnatal development.

scholarly journals Dopamine Increases Excitability of Pyramidal Neurons in Primate Prefrontal Cortex

2000 ◽  
Vol 84 (6) ◽  
pp. 2799-2809 ◽  
Author(s):  
Darrell A. Henze ◽  
Guillermo R. González-Burgos ◽  
Nathaniel N. Urban ◽  
David A. Lewis ◽  
German Barrionuevo
Keyword(s):  
Prefrontal Cortex ◽  
Action Potential ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Initiation Site ◽  
D1 Receptor ◽  
Resting Membrane Potential ◽  
Cellular Mechanisms

Dopaminergic modulation of neuronal networks in the dorsolateral prefrontal cortex (PFC) is believed to play an important role in information processing during working memory tasks in both humans and nonhuman primates. To understand the basic cellular mechanisms that underlie these actions of dopamine (DA), we have investigated the influence of DA on the cellular properties of layer 3 pyramidal cells in area 46 of the macaque monkey PFC. Intracellular voltage recordings were obtained with sharp and whole cell patch-clamp electrodes in a PFC brain-slice preparation. All of the recorded neurons in layer 3 ( n = 86) exhibited regular spiking firing properties consistent with those of pyramidal neurons. We found that DA had no significant effects on resting membrane potential or input resistance of these cells. However DA, at concentrations as low as 0.5 μM, increased the excitability of PFC cells in response to depolarizing current steps injected at the soma. Enhanced excitability was associated with a hyperpolarizing shift in action potential threshold and a decreased first interspike interval. These effects required activation of D1-like but not D2-like receptors since they were inhibited by the D1 receptor antagonist SCH23390 (3 μM) but not significantly altered by the D2 antagonist sulpiride (2.5 μM). These results show, for the first time, that DA modulates the activity of layer 3 pyramidal neurons in area 46 of monkey dorsolateral PFC in vitro. Furthermore the results suggest that, by means of these effects alone, DA modulation would generally enhance the response of PFC pyramidal neurons to excitatory currents that reach the action potential initiation site.

Apamin-Sensitive Conductance Mediates the K+ Current Response During Chemical Ischemia in CA3 Pyramidal Cells

1999 ◽  
Vol 82 (6) ◽  
pp. 2876-2882 ◽  
Author(s):  
Mitsuo Tanabe ◽  
Masahiro Mori ◽  
Beat H. Gähwiler ◽  
Urs Gerber
Keyword(s):  
Pyramidal Neurons ◽  
Outward Current ◽  
Pyramidal Cells ◽  
Current Response ◽  
Kinase C ◽  
Hippocampal Ca3 ◽  
Organotypic Slice Cultures ◽  
K Current ◽  
Ca3 Pyramidal Neurons ◽  
Ca3 Pyramidal Cells

Pyramidal cells typically respond to ischemia with initial transient hyperpolarization, which may represent a neuroprotective response. To identify the conductance underlying this hyperpolarization in CA3 pyramidal neurons of rat hippocampal organotypic slice cultures, recordings were obtained using the single-electrode voltage-clamp technique. Brief chemical ischemia (2 mM 2-deoxyglucose and 3 mM NaN3, for 4 min) induced a response mediated by an increase in K+ conductance. This current was blocked by intracellular application of the Ca2+ chelator, bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA), reduced with low external [Ca2+], and inhibited by a selective L-type Ca2+ channel inhibitor, isradipine, consistent with the activation of a Ca2+-dependent K+ conductance. Experiments with charybdotoxin (10 nM) and tetraethylammonium (TEA; 1 mM), or with the protein kinase C activator, phorbol 12,13-diacetate (PDAc; 3 μM), ruled out an involvement of a large conductance–type or an apamin-insensitive small conductance, respectively. In the presence of apamin (1 μM), however, the outward current was significantly reduced. These results demonstrate that in rat hippocampal CA3 pyramidal neurons an apamin-sensitive Ca2+-dependent K+ conductance is activated in response to brief ischemia generating a pronounced outward current.

Spontaneous release of GABA activates GABAB receptors and controls network activity in the neonatal rat hippocampus

1996 ◽  
Vol 76 (2) ◽  
pp. 1036-1046 ◽  
Author(s):  
H. A. McLean ◽  
O. Caillard ◽  
R. Khazipov ◽  
Y. Ben-Ari ◽  
J. L. Gaiarsa
Keyword(s):  
Divalent Cation ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Gabab Receptors ◽  
Neonatal Rat ◽  
Network Activity ◽  
Pipette Solution ◽  
Ca3 Pyramidal Neurons ◽  
Ca3 Pyramidal Cells ◽  
Cgp 35348

1. We investigated the effects of the selective gamma-aminobutyric acid-B (GABAB) receptor antagonist, P-3 aminopropyl-P-diethoxymethyl phosphoric acid (CGP 35348), on spontaneous and evoked postsynaptic potentials (PSPs) and currents (PSCs) in CA3 pyramidal cells and interneurons of hippocampal slices obtained between postnatal day 3 and 7 with the use of intracellular and whole cell recording techniques. The intracellular pipette solution contained either 2 M CsCl or 50 mM 2(triethylamino)-N-(2,6-dimethylphenyl) acetamine (QX314) dissolved in 2 M KMeSO4. Cesium and QX314 block postsynaptic responses mediated by GABAB receptors. 2. Under control conditions, bath application of CGP 35348 (0.5-1 mM) progressively increased the duration of spontaneous and evoked polysynaptic giant GABAergic PSPs leading to the appearance of ictal-like discharges. The effects of CGP 35348 were dose dependent and voltage independent. 3. In CA3 pyramidal neurons, CGP 35348 (0.5 mM) had no effect on monosynaptic GABAergic inhibitory PSPs (IPSPs) that were isolated in the presence of ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and D(-)2-amino-5-phosphovaleric acid (D-APV, 50 microM). Similarly, CGP 35348 (0.5 mM) had no effect on monosynaptic glutamatergic excitatory PSPs (EPSPs) that were isolated in the presence of bicuculline (10 microM) and high divalent cation artificial cerebrospinal fluid (ACSF; 6 mM Mg2+/4 mM Ca2+). 4. In CA3 pyramidal neurons exposed to CNQX (20 microM) and D-APV (50 microM), application of the potassium channel blocker 4-aminopyridine (4-AP, 50 microM) generated synchronous giant GABAergic PSPS that were blocked in the presence of high divalent cation ACSF (6 mM Mg2+/4 mM Ca2+) or bicuculline (10 microM). The duration of these synchronous GABAergic PSPs was prolonged in the presence of CGP 35348 (0.5 mM) but did not lead to the appearance of ictal-like discharges. 5. In the presence of bicuculline, interictal giant glutamatergic potentials were observed in simultaneously recorded CA3 pyramidal cells and interneurons. CGP 35348 (0.5 mM) progressively increased the duration of these bicuculline-induced glutamatergic bursts leading to the simultaneous appearance of ictal discharges in both pyramidal cells and interneurons. 6. These results suggest that in the neonatal CA3 hippocampal region, when synchronous giant polysynaptic GABAergic PSPs are present (i.e., under basal, control conditions), spontaneously released GABA reaches a critical level and activates GABAB receptors on both pyramidal cells and interneurons thus regulating the level of glutamatergic and GABAergic activity in the CA3 neuronal network.

scholarly journals Action potential counting at giant mossy fiber terminals gates information transfer in the hippocampus

2017 ◽  
Author(s):  
Simon Chamberland ◽  
Yulia Timofeeva ◽  
Alesya Evstratova ◽  
Kirill Volynski ◽  
Katalin Tóth
Keyword(s):  
Information Transfer ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Pyramidal Cells ◽  
Short Term ◽  
Ca3 Pyramidal Neurons ◽  
Presynaptic Calcium ◽  
Ca3 Pyramidal Cells ◽  
The Brain

AbstractHippocampal mossy fibers have long been recognized as conditional detonators owing to prominent short-term facilitation, but the patterns of activity required to fire postsynaptic CA3 pyramidal neurons remain poorly understood. We show that mossy fibers count the number of spikes to transmit information to CA3 pyramidal cells through a distinctive interplay between presynaptic calcium dynamics, buffering and vesicle replenishment. This identifies a previously unexplored information coding mechanism in the brain.

Analysis of voltage-gated and synaptic conductances contributing to network excitability defects in the mutant mouse tottering

1994 ◽  
Vol 71 (1) ◽  
pp. 1-10 ◽  
Author(s):  
S. A. Helekar ◽  
J. L. Noebels
Keyword(s):  
Gabaa Receptor ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Channel Blockers ◽  
Gamma Aminobutyric Acid ◽  
Voltage Gated ◽  
Voltage Dependent ◽  
Prolonged Duration ◽  
Ca3 Pyramidal Neurons ◽  
The Difference

1. Intracellular current- and voltage-clamp recordings were carried out in CA3 pyramidal neurons from hippocampal slices of adult tg/tg mice and their coisogenic C57BL/6J (+/+) controls with the use of the single-electrode switch-clamp technique. The principal aim of this study was to investigate the mechanisms responsible for the tg gene-linked prolongation (mean 60%) of a giant synaptic response, the potassium-induced paroxysmal depolarizing shift (PDS) at depolarized membrane potentials (Vm -47 to -54 mV) during synchronous network bursting induced by 10 mM potassium ([K+]o). 2. To examine the role of intrinsic voltage-dependent conductances underlying the mutant PDS prolongation, neurons were voltage clamped by the use of microelectrodes filled with 100 mM QX-314 or QX-222 chloride (voltage-gated sodium channel blockers) and 2 M cesium sulphate (potassium channel blocker). The whole-cell currents active during the PDS showed a significantly prolonged duration (mean 34%) at depolarized Vms in tg/tg compared with +/+ cells, indicating that a defect in voltage-dependent conductances is unlikely to completely account for the mutant phenotype. 3. Bath application of 40 microM (DL)-2-aminophosphonovalerate (DL-APV) produced a 30% reduction in PDS duration in both genotypes but failed to significantly alter the tg gene-linked prolongation compared with the wild type. These data indicate that the mutant PDS abnormality does not result from a selective increase of the N-methyl-D-aspartate (NMDA) receptor-mediated excitatory synaptic component. 4. Blockade of gamma-aminobutyric acid-A (GABAA) transmission with picrotoxin (50 microM) or bicuculline (1–5 microM) completely eliminated the difference in PDS duration between the genotypes. Furthermore, although both GABAA receptor antagonists increased the mean PDS duration in +/+ neurons, they did not significantly alter it in tg/tg neurons. These findings are consistent with a reduction in GABAA receptor-mediated synaptic inhibition during bursting in the tg CA3 hippocampal network. 5. To test this hypothesis, bursting CA3 pyramidal neurons were loaded intracellularly with chloride by the use of KCl-filled microelectrodes to examine the effect of reversing the hyperpolarizing chloride-dependent GABAA receptor-mediated inhibitory postsynaptic component of the PDS. Chloride loading prolonged PDS duration in both genotypes, but the increase was greater in +/+ than in tg/tg neurons, indicating that a smaller GABAA inhibitory postsynaptic potential (IPSP) component was reversed in the mutant.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Computational Analysis of the Impact of Chronic Stress on Intrinsic and Synaptic Excitability in the Hippocampus

2010 ◽  
Vol 103 (6) ◽  
pp. 3070-3083 ◽  
Author(s):  
Rishikesh Narayanan ◽  
Sumantra Chattarji
Keyword(s):  
Chronic Stress ◽  
Pyramidal Neurons ◽  
Three Dimensional ◽  
Input Resistance ◽  
Synaptic Potentiation ◽  
Synaptic Inputs ◽  
Hippocampal Ca3 ◽  
Ca3 Pyramidal Neurons ◽  
Dendritic Atrophy ◽  
The Impact

Dendritic atrophy and impaired long-term synaptic potentiation (LTP) are hallmarks of chronic stress-induced plasticity in the hippocampus. It has been hypothesized that these disparate structural and physiological correlates of stress lead to hippocampal dysfunction by reducing postsynaptic dendritic surface, thereby adversely affecting the availability of synaptic inputs and suppressing LTP. Here we examine the validity of this framework using biophysical models of hippocampal CA3 pyramidal neurons. To statistically match with the experimentally observed region specificity of stress-induced atrophy, we use an algorithm to systematically prune three-dimensional reconstructions of CA3 pyramidal neurons. Using this algorithm, we build a biophysically realistic computational model to analyze the effects of stress on intrinsic and synaptic excitability. We find that stress-induced atrophy of CA3 dendrites leads to an increase in input resistance, which depends exponentially on the percentage of neuronal atrophy. This increase translates directly into higher spiking frequencies in response to both somatic current injections and synaptic inputs at various locations along the dendritic arbor. Remarkably, we also find that the dendritic regions that manifest atrophy-induced synaptic hyperexcitability are governed by the region specificity of the underlying dendritic atrophy. Coupled with experimentally observed modulation of N-methyl-d-aspartate receptor currents, such hyperexcitability could tilt the balance of plasticity mechanisms in favor of synaptic potentiation over depression. Thus paradoxically, our results suggest that stress may impair hippocampal learning and memory, not by directly inhibiting LTP, but because of stress-induced facilitation of intrinsic and synaptic excitability and the consequent imbalance in bidirectional synaptic plasticity.

Differential Impact of Miniature Synaptic Potentials on the Soma and Dendrites of Pyramidal Neurons In Vivo

1997 ◽  
Vol 78 (3) ◽  
pp. 1735-1739 ◽  
Author(s):  
Denis Paré ◽  
Elen Lebel ◽  
Eric J. Lang
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Differential Impact ◽  
Synaptic Potentials ◽  
Ampa Antagonists ◽  
Intact Brain ◽  
The Impact

Paré, Denis, Elen LeBel, and Eric J. Lang. Differential impact of miniature synaptic potentials on the somata and dendrites of pyramidal neurons in vivo. J. Neurophysiol. 78: 1735–1739, 1997. We studied the impact of transmitter release resistant to tetrodotoxin (TTX) in morphologically identified neocortical pyramidal neurons recorded intracellularly in barbiturate-anesthetized cats. It was observed that TTX-resistant release occurs in pyramidal neurons in vivo and at much higher frequencies than was previously reported in vitro. Further, in agreement with previous findings indicating that GABAergic and glutamatergic synapses are differentially distributed in the somata and dendrites of pyramidal cells, we found that most miniature synaptic potentials were sensitive to γ-aminobutyric acid-A (GABAA) or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonists in presumed somatic and dendritic impalements, respectively. Pharmacological blockage of spontaneous synaptic events produced large increases in input resistance that were more important in dendritic (≈50%) than somatic (≈10%) impalements. These findings imply that in the intact brain, pyramidal neurons are submitted to an intense spike-independent synaptic bombardment that decreases the space constant of the cells. These results should be taken into account when extrapolating in vitro findings to intact brains.

Modulation of the Ca2+-Activated K+ Current sI AHP by aPhosphatase-Kinase Balance Under Basal Conditions inRat CA1 Pyramidal Neurons

1998 ◽  
Vol 79 (6) ◽  
pp. 3252-3256 ◽  
Author(s):  
Paola Pedarzani ◽  
Michael Krause ◽  
Trude Haug ◽  
Johan F. Storm ◽  
Walter Stühmer
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Phosphodiesterase Inhibitors ◽  
Gradual Decrease ◽  
Patch Clamp Technique ◽  
Hippocampal Pyramidal Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Type Iv ◽  
Whole Cell Patch Clamp ◽  
Firing Properties

Pedarzani, Paola, Michael Krause, Trude Haug, Johan F. Storm, and Walter Stühmer. Modulation of the Ca2+-activated K+ current s I AHP by a phosphatase-kinase balance under basal conditions in rat CA1 pyramidal neurons. J. Neurophysiol. 79: 3252–3256, 1998. The slow Ca2+-activated K+ current, s I AHP, underlying spike frequency adaptation, was recorded with the whole cell patch-clamp technique in CA1 pyramidal neurons in rat hippocampal slices. Inhibitors of serine/threonine protein phosphatases (microcystin, calyculin A, cantharidic acid) caused a gradual decrease of s I AHP amplitude, suggesting the presence of a basal phosphorylation-dephosphorylation turnover regulating s I AHP. Because selective calcineurin (PP-2B) inhibitors did not affect the amplitude of s I AHP, protein phosphatase 1 (PP-1) or 2A (PP-2A) are most likely involved in the basal regulation of this current. The ATP analogue, ATP-γ-S, caused a gradual decrease in the s I AHP amplitude, supporting a role of protein phosphorylation in the basal modulation of s I AHP. When the protein kinase A (PKA) inhibitor adenosine-3′,5′-monophosphorothioate, Rp-isomer (Rp-cAMPS) was coapplied with the phosphatase inhibitor microcystin, it prevented the decrease in the s I AHP amplitude that was observed when microcystin alone was applied. Furthermore, inhibition of PKA by Rp-cAMPS led to an increase in the s I AHP amplitude. Finally, an adenylyl cyclase inhibitor (SQ22,536) and adenosine 3′,5′-cyclic monophosphate-specific type IV phosphodiesterase inhibitors (Ro 20–1724 and rolipram) led to an increase or a decrease in the s I AHP amplitude, respectively. These findings suggest that a balance between basally active PKA and a phosphatase (PP-1 or PP-2A) is responsible for the tonic modulation of s I AHP, resulting in a continuous modulation of excitability and firing properties of hippocampal pyramidal neurons.

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