scholarly journals Synaptic and Nonsynaptic Contributions to Giant IPSPs and Ectopic Spikes Induced by 4-Aminopyridine in the Hippocampus In Vitro

2001 ◽  
Vol 85 (3) ◽  
pp. 1246-1256 ◽  
Author(s):  
Roger D. Traub ◽  
Rea Bibbig ◽  
Antje Piechotta ◽  
Reas Draguhn ◽  
Dietmar Schmitz
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Action Potentials ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Recent Experimental Data ◽  
Large Network ◽  
Principal Cells ◽  
Network Bursts

Hippocampal slices bathed in 4-aminopyridine (4-AP, ≤200 μM) exhibit 1) spontaneous large inhibitory postsynaptic potentials (IPSPs) in pyramidal cells, which occur without the necessity of fast glutamatergic receptors, and which hence are presumed to arise from coordinated firing in populations of interneurons; 2) spikes of variable amplitude, presumed to be of antidromic origin, in some pyramidal cells during the large IPSP; 3) bursts of action potentials in selected populations of interneurons, occurring independently of fast glutamatergic and of GABAAreceptors. We have used neuron pairs, and a large network model (3,072 pyramidal cells, 384 interneurons), to examine how these phenomena might be inter-related. Network bursts in electrically coupled interneurons have previously been shown to be possible with dendritic gap junctions, when the dendrites were capable of spike initiation, and when action potentials could cross from cell to cell via gap junctions; recent experimental data showing that dendritic gap junctions between cortical interneurons lead to coupling potentials of only about 0.5 mV argue against this mechanism, however. We now show that axonal gap junctions between interneurons could also lead to network bursts; this concept is consistent with the occurrence of spikelets and partial spikes in at least some interneurons in 4-AP. In our model, spontaneous antidromic action potentials can induce spikelets and action potentials in principal cells during the large IPSP. The probability of observing this type of activity increases significantly when axonal gap junctions also exist between pyramidal cells. Sufficient antidromic activity in the model can lead to epileptiform bursts, independent of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors, in some principal cells, preceded by IPSPs and spikelets. The model predicts that gap junction blockers should suppress large IPSPs observed in 4-AP and should also reduce the probability of observing antidromic activity, or bursting, in pyramidal cells. Experiments show that, indeed, the gap junction blocking compound carbenoxolone does suppress spontaneous large IPSCs, occurring in 4-AP plus ionotropic glutamate blockers, together with a GABAB receptor blocker; carbenoxolone also suppresses large, fast inward currents, corresponding to ectopic spikes, which occur in 4-AP. Carbenoxolone does not suppress large depolarizing IPSPs induced by tetanic stimulation. We conclude that in 4-AP, axonal gap junctions could, at least in principle, account in part for both the large IPSPs, and for the antidromic activity in pyramidal neurons.

Network Interactions Mediated by New Excitatory Connections Between CA1 Pyramidal Cells in Rats With Kainate-Induced Epilepsy

2002 ◽  
Vol 87 (3) ◽  
pp. 1655-1658 ◽  
Author(s):  
Bret N. Smith ◽  
F. Edward Dudek
Keyword(s):  
Status Epilepticus ◽  
Action Potentials ◽  
Cell Layer ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Ca1 Pyramidal Cells ◽  
Axon Sprouting ◽  
Synaptic Interactions ◽  
Network Bursts ◽  
Ca1 Area

Axon sprouting and synaptic reorganization in the hippocampus are associated with the development of seizures in temporal lobe epilepsy. Synaptic interactions among CA1 pyramidal cells were examined in fragments of hippocampal slices containing only the CA1 area from saline- and kainate-treated rats. Glutamate microapplication to the pyramidal cell layer increased excitatory postsynaptic current (EPSC) frequency, but only in rats with kainate-induced epilepsy. In bicuculline, action potentials evoked in single pyramidal cells increased the frequency of network bursts only in slices from rats with kainate-induced epilepsy. These data further support the hypothesis that excitatory connections between CA1 pyramidal cells increase after kainate-induced status epilepticus.

Mechanisms of Electrical Coupling Between Pyramidal Cells

1997 ◽  
Vol 78 (6) ◽  
pp. 3107-3116 ◽  
Author(s):  
Edward J. Vigmond ◽  
Jose L. Perez Velazquez ◽  
Taufik A. Valiante ◽  
BERJ L. Bardakjian ◽  
Peter L. Carlen
Keyword(s):  
Electric Field ◽  
Gap Junctions ◽  
Small Amplitude ◽  
Hippocampal Slices ◽  
Electrical Coupling ◽  
Pyramidal Cells ◽  
Action Potential Firing ◽  
Field Effects ◽  
Gap Junctional

Vigmond, Edward J., Jose L. Perez Velazquez, Taufik A. Valiante, Berj L. Bardakjian, and Peter L. Carlen. Mechanisms of electrical coupling between pyramidal cells. J. Neurophysiol. 78: 3107–3116, 1997. Direct electrical coupling between neurons can be the result of both electrotonic current transfer through gap junctions and extracellular fields. Intracellular recordings from CA1 pyramidal neurons of rat hippocampal slices showed two different types of small-amplitude coupling potentials: short-duration (5 ms) biphasic spikelets, which resembled differentiated action potentials and long-duration (>20 ms) monophasic potentials. A three-dimensional morphological model of a pyramidal cell was employed to determine the extracellular field produced by a neuron and its effect on a nearby neuron resulting from both gap junctional and electric field coupling. Computations were performed with a novel formulation of the boundary element method that employs triangular elements to discretize the soma and cylindrical elements to discretize the dendrites. An analytic formula was derived to aid in computations involving cylindrical elements. Simulation results were compared with biological recordings of intracellular potentials and spikelets. Field effects produced waveforms resembling spikelets although of smaller magnitude than those recorded in vitro. Gap junctional electrotonic connections produced waveforms resembling small-amplitude excitatory postsynaptic potentials. Intracellular electrode measurements were found inadequate for ascertaining membrane events because of externally applied electric fields. The transmembrane voltage induced by the electric field was highly spatially dependent in polarity and wave shape, as well as being an order of magnitude larger than activity measured at the electrode. Membrane voltages because of electrotonic current injection across gap junctions were essentially constant over the cell and were accurately depicted by the electrode. The effects of several parameters were investigated: 1) decreasing the ratio of intra to extracellular conductivity reduced the field effects; 2) the tree structure had a major impact on the intracellular potential; 3) placing the gap junction in the dendrites introduced a time delay in the gap junctional mediated electrotonic potential, as well as deceasing the potential recorded by the somatic electrode; and 4) field effects decayed to one-half of their maximum strength at a cell separation of ∼20 μm. Results indicate that the in vitro measured spikelets are unlikely to be mediated by gap junctions and that a spikelet produced by the electric field of a single source cell has the same waveshape as the measured spikelet but with a much smaller amplitude. It is hypothesized that spikelets are a manifestation of the simultaneous electric field effects from several local cells whose action potential firing is synchronized.

scholarly journals Two Drosophila Innexins Are Expressed in Overlapping Domains and Cooperate to Form Gap-Junction Channels

2000 ◽  
Vol 11 (7) ◽  
pp. 2459-2470 ◽  
Author(s):  
Lucy A. Stebbings ◽  
Martin G. Todman ◽  
Pauline Phelan ◽  
Jonathan P. Bacon ◽  
Jane A. Davies
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Ectopic Expression ◽  
In Vivo Studies ◽  
Electrophysiological Properties ◽  
Gap Junction Channels ◽  
Overlapping Domains ◽  
In Vitro Data

Members of the innexin protein family are structural components of invertebrate gap junctions and are analogous to vertebrate connexins. Here we investigate two Drosophila innexin genes,Dm-inx2 and Dm-inx3 and show that they are expressed in overlapping domains throughout embryogenesis, most notably in epidermal cells bordering each segment. We also explore the gap-junction–forming capabilities of the encoded proteins. In pairedXenopus oocytes, the injection of Dm-inx2mRNA results in the formation of voltage-sensitive channels in only ∼ 40% of cell pairs. In contrast, Dm-Inx3 never forms channels. Crucially, when both mRNAs are coexpressed, functional channels are formed reliably, and the electrophysiological properties of these channels distinguish them from those formed by Dm-Inx2 alone. We relate these in vitro data to in vivo studies. Ectopic expression ofDm-inx2 in vivo has limited effects on the viability ofDrosophila, and animals ectopically expressingDm-inx3 are unaffected. However, ectopic expression of both transcripts together severely reduces viability, presumably because of the formation of inappropriate gap junctions. We conclude that Dm-Inx2 and Dm-Inx3, which are expressed in overlapping domains during embryogenesis, can form oligomeric gap-junction channels.

Control of gap junction formation in canine trachea by arachidonic acid metabolites

1986 ◽  
Vol 250 (3) ◽  
pp. C495-C505 ◽  
Author(s):  
R. Agrawal ◽  
E. E. Daniel
Keyword(s):  
Arachidonic Acid ◽  
Gap Junctions ◽  
Gap Junction ◽  
Direct Effects ◽  
Leukotriene C4 ◽  
Lipoxygenase Pathway ◽  
Junction Formation ◽  
Acid Metabolites ◽  
Pg E2

This study examined whether the synthesis of the metabolites of arachidonic acid (AA) was involved in gap junction formation by 4-aminopyridine (4-AP) treatment in vitro in canine trachealis. Studies were made of the effects on gap junction formation of putative inhibitors of the cyclooxygenase and of both this and the lipoxygenase pathway of AA metabolism and the direct effects of prostaglandins (PG) E2 and I2. The number of gap junctions of similar size was increased after brief exposure to 4-AP. After indomethacin (IDM), 4-AP treatment decreased the number of gap junctions but did not affect their size. Pretreatment with 5,8,11,14-eicosatetraynoic acid or nordihydroguiaretic acid, putative inhibitors of cyclooxygenase and lipoxygenase enzymes, inhibited both the 4-AP-induced increase and decrease in the number of gap junctions. FPL 55712, a putative antagonist of leukotriene C4, did not alter either the number or the size of gap junctions when added alone or in combination with IDM. AA alone increased the number of gap junctions, but after IDM, AA decreased the number of gap junctions compared with the controls. Incubation of trachealis strips in vitro for 30 min with PGE2 increased the number of gap junctions by about threefold along with an increase in the size of the gap junctions. Similar incubation with PGI2, however, increased the number of gap junctions by approximately 60% without any change in the size. In the course of some control experiments, an interaction between carbachol and alcohol was observed such that alcohol caused an IDM-sensitive relaxation of carbachol-induced contractions, which was not observed when serotonin was the contractile agent. These results strongly suggest that PGE2 and PGI2 increase the formation of gap junctions in canine trachealis and that these prostanoids are released by 4-AP treatment. Leukotrienes may also be inhibitory in the formation of gap junctions, but FPL 55712 did not affect either the increase or the decrease in gap junctions after 4-AP.

Calcium-dependent current generating the afterhyperpolarization of hippocampal neurons

1986 ◽  
Vol 55 (6) ◽  
pp. 1268-1282 ◽  
Author(s):  
B. Lancaster ◽  
P. R. Adams
Keyword(s):  
Voltage Clamp ◽  
Hippocampal Neurons ◽  
Hippocampal Slices ◽  
Outward Current ◽  
Pyramidal Cells ◽  
Resting Potential ◽  
Tail Current ◽  
Calcium Dependent ◽  
K Current

A single-electrode voltage-clamp technique was employed on in vitro hippocampal slices to examine the membrane current responsible for the slow afterhyperpolarization (AHP) in CA1 pyramidal cells. This was achieved by using conventional procedures to evoke an AHP in current clamp, followed rapidly by a switch into voltage clamp (hybrid clamp). The AHP current showed a dependence on extracellular K+, which was close to that predicted for a K+ current by the Nernst equation. The AHP current could be blocked by Cd2+ or norepinephrine. Although the AHP current showed a requirement for voltage-dependent Ca2+ entry, the current did not show any clear intrinsic voltage dependence. Once activated, AHP current is not turned off by hyperpolarizing the membrane potential. The effects of norepinephrine, Cd2+, and tetraethylammonium (TEA) were used to identify an AHP current component to the outward current evoked by depolarizing voltage commands from holding potentials that approximate to the resting potential for these cells. The AHP current can contribute significantly to the outward current during the depolarizing command. Upon repolarization it is evident as a slow outward tail current. This slow tail current had the same time constant as AHP currents evoked by hybrid clamp. Fast components to the tail currents were also observed. These were sensitive to Cd2+ and TEA. They probably represent a voltage-sensitive gKCa, sometimes termed C-current. The strong sensitivity to voltage and TEA displayed by the conventionally described gKCa (IC) are properties inconsistent with the AHP. It seems likely that the AHP current (IAHP) represents a Ca2+-activated K+ current separate from IC and that these two currents coexist in the same cell.

Sharp Wave-Like Activity in the Hippocampus In Vitro in Mice Lacking the Gap Junction Protein Connexin 36

2003 ◽  
Vol 89 (4) ◽  
pp. 2046-2054 ◽  
Author(s):  
Isabel Pais ◽  
Sheriar G. Hormuzdi ◽  
Hannah Monyer ◽  
Roger D. Traub ◽  
Ian C. Wood ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Frequency Oscillation ◽  
Connexin 36 ◽  
Sharp Wave ◽  
Bath Application ◽  
Junction Protein ◽  
Gap Junction Protein ◽  
Electrical Signaling

Bath application of kainate (100–300 nM) induced a persistent gamma-frequency (30–80 Hz) oscillation that could be recorded in stratum radiatum of the CA3 region in vitro. We have previously described that in knockout mice lacking the gap junction protein connexin 36 (Cx36KO), γ-frequency oscillations are reduced but still present. We now demonstrate that in the Cx36KO mice, but not in wild-type (WT), large population field excitatory postsynaptic potentials, or sharp wave-burst discharges, also occurred during the on-going γ-frequency oscillation. These spontaneous burst discharges were not seen in WT mice. Burst discharges in the Cx36KO mice occurred with a mean frequency of 0.23 ± 0.11 Hz and were accompanied by a series of fast (approximately 60–115 Hz) population spikes or “ripple” oscillations in many recordings. Intracellular recordings from CA3 pyramidal cells showed that the burst discharges consisted of a depolarizing response and presumed coupling potentials (spikelets) could occasionally be seen either before or during the burst discharge. The burst discharges occurring in Cx36KO mice were sensitive to gap junctions blockers as they were fully abolished by carbenoxolone (200 μM). In control mice we made several attempts to replicate this pattern of sharp wave activity/ripples occurring with the on-going kainate-evoked γ-frequency oscillation by manipulating synaptic and electrical signaling. Partial disruption of inhibition, in control slices, by bath application of the γ-aminobutyric acid-A (GABAA) receptor antagonist bicuculline (1–4 μM) completely abolished all γ-frequency activity before any burst discharges occurred. Increasing the number of open gap junctions in control slices by using trimethylamine (TMA; 2–10 mM), in conjunction with kainate, failed to elicit any sharp wave bursts or fast ripples. However, bath application of the potassium channel blocker 4-aminopyridine (4-AP; 20–80 μM) produced a pattern of activity in control mice (13/16 slices), consisting of burst discharges occurring in conjunction with kainate-evoked γ-frequency oscillations, that was similar to that seen in Cx36KO mice. In a few cases ( n = 9) the burst discharges were accompanied by fast ripple oscillations. Carbenoxolone also fully blocked the 4-AP-evoked burst discharges ( n = 5). Our results show that disruption of electrical signaling in the interneuronal network can, in the presence of kainate, lead to the spontaneous generation of sharp wave/ripple activity similar to that observed in vivo. This suggests a complex role for electrically coupled interneurons in the generation of hippocampal network activity.

Characterization of an early afterhyperpolarization after a brief train of action potentials in rat hippocampal neurons in vitro

1990 ◽  
Vol 63 (1) ◽  
pp. 72-81 ◽  
Author(s):  
A. Williamson ◽  
B. E. Alger
Keyword(s):  
Action Potentials ◽  
Hippocampal Neurons ◽  
Pyramidal Cells ◽  
Chloride Ions ◽  
Membrane Potentials ◽  
Resting Potential ◽  
K Channel ◽  
Delayed Rectifier ◽  
Extracellular Potassium

1. In rat hippocampal pyramidal cells in vitro, a brief train of action potentials elicited by direct depolarizing current pulses injected through an intracellular recording electrode is followed by a medium-duration afterhyperpolarization (mAHP) and a longer, slow AHP. We studied the mAHP with the use of current-clamp techniques in the presence of dibutyryl cyclic adenosine 3',5'-monophosphate (cAMP) to block the slow AHP and isolate the mAHP. 2. The mAHP evoked at hyperpolarized membrane potentials was complicated by a potential generated by the anomalous rectifier current, IQ. The mAHP is insensitive to chloride ions (Cl-), whereas it is sensitive to the extracellular potassium concentration ([K+]o). 3. At slightly depolarized levels, the mAHP is partially Ca2+ dependent, being enhanced by increased [Ca2+]o and BAY K 8644 and depressed by decreased [Ca2+]o, nifedipine, and Cd2+. The Ca2(+)-dependent component of the mAHP was also reduced by 100 microM tetraethylammonium (TEA) and charybdotoxin (CTX), suggesting it is mediated by the voltage- and Ca2(+)-dependent K+ current, IC. 4. Most of the Ca2(+)-independent mAHP was blocked by carbachol, implying that IM plays a major role. In a few cells, a small Ca2(+)- and carbachol-insensitive mAHP component was detectable, and this component was blocked by 10 mM TEA, suggesting it was mediated by the delayed rectifier current, IK. The K+ channel antagonist 4-aminopyridine (4-AP, 500 microM) did not reduce the mAHP. 5. We infer that the mAHP is a complex potential due either to IQ or to the combined effects of IM and IC. The contributions of each current depend on the recording conditions, with IC playing a role when the cells are activated from depolarized potentials and IM dominating at the usual resting potential. IQ is principally responsible for the mAHP recorded at hyperpolarized membrane potentials.

scholarly journals The Functional Implications of Endothelial Gap Junctions and Cellular Mechanics in Vascular Angiogenesis

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 237 ◽  
Author(s):  
Takayuki Okamoto ◽  
Haruki Usuda ◽  
Tetsuya Tanaka ◽  
Koichiro Wada ◽  
Motomu Shimaoka
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Gap Junctions ◽  
Gap Junction ◽  
Cancer Cells ◽  
Tumor Development ◽  
Tube Formation ◽  
Cellular Mechanics

Angiogenesis—the sprouting and growth of new blood vessels from the existing vasculature—is an important contributor to tumor development, since it facilitates the supply of oxygen and nutrients to cancer cells. Endothelial cells are critically affected during the angiogenic process as their proliferation, motility, and morphology are modulated by pro-angiogenic and environmental factors associated with tumor tissues and cancer cells. Recent in vivo and in vitro studies have revealed that the gap junctions of endothelial cells also participate in the promotion of angiogenesis. Pro-angiogenic factors modulate gap junction function and connexin expression in endothelial cells, whereas endothelial connexins are involved in angiogenic tube formation and in the cell migration of endothelial cells. Several mechanisms, including gap junction function-dependent or -independent pathways, have been proposed. In particular, connexins might have the potential to regulate cell mechanics such as cell morphology, cell migration, and cellular stiffness that are dynamically changed during the angiogenic processes. Here, we review the implication for endothelial gap junctions and cellular mechanics in vascular angiogenesis.

Evidence from simultaneous intracellular recordings in rat hippocampal slices that area CA3 pyramidal cells innervate dentate hilar mossy cells

1994 ◽  
Vol 72 (5) ◽  
pp. 2167-2180 ◽  
Author(s):  
H. E. Scharfman
Keyword(s):  
Pyramidal Cell ◽  
Action Potentials ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Probability Of Failure ◽  
Mossy Cells ◽  
Mossy Cell ◽  
Ca3 Pyramidal Cells ◽  
Area Ca3

1. Simultaneous intracellular recordings of area CA3 pyramidal cells and dentate hilar “mossy” cells were made in rat hippocampal slices to test the hypothesis that area CA3 pyramidal cells excite mossy cells monosynaptically. Mossy cells and pyramidal cells were differentiated by location and electrophysiological characteristics. When cells were impaled near the border of area CA3 and the hilus, their identity was confirmed morphologically after injection of the marker Neurobiotin. 2. Evidence for monosynaptic excitation of a mossy cell by a pyramidal cell was obtained in 7 of 481 (1.4%) paired recordings. In these cases, a pyramidal cell action potential was followed immediately by a 0.40 to 6.75 (mean, 2.26) mV depolarization in the simultaneously recorded mossy cell (mossy cell membrane potentials, -60 to -70 mV). Given that pyramidal cells used an excitatory amino acid as a neurotransmitter (Cotman and Nadler 1987; Ottersen and Storm-Mathisen 1987) and recordings were made in the presence of the GABAA receptor antagonist bicuculline (25 microM), it is likely that the depolarizations were unitary excitatory postsynaptic potentials (EPSPs). 3. Unitary EPSPs of mossy cells were prone to apparent “failure.” The probability of failure was extremely high (up to 0.72; mean = 0.48) if the effects of all presynaptic action potentials were examined, including action potentials triggered inadvertently during other spontaneous EPSPs of the mossy cell. Probability of failure was relatively low (as low as 0; mean = 0.24) if action potentials that occurred during spontaneous activity of the mossy cell were excluded. These data suggest that unitary EPSPs produced by pyramidal cells are strongly affected by concurrent synaptic inputs to the mossy cell. 4. Unitary EPSPs were not clearly affected by manipulation of the mossy cell's membrane potential. This is consistent with the recent report that area CA3 pyramidal cells innervate distal dendrites of mossy cells (Kunkel et al. 1993). Such a distal location also may contribute to the high incidence of apparent failures. 5. Characteristics of unitary EPSPs generated by pyramidal cells were compared with the properties of the unitary EPSPs produced by granule cells. In two slices, pyramidal cell and granule cell inputs to the same mossy cell were compared. In other slices, inputs to different mossy cells were compared. In all experiments, unitary EPSPs produced by granule cells were larger in amplitude but similar in time course to unitary EPSPs produced by pyramidal cells. Probability of failure was lower and paired-pulse facilitation more common among EPSPs triggered by granule cells.(ABSTRACT TRUNCATED AT 400 WORDS)

On the synchronous activity induced by 4-aminopyridine in the CA3 subfield of juvenile rat hippocampus

1993 ◽  
Vol 70 (3) ◽  
pp. 1018-1029 ◽  
Author(s):  
M. Avoli ◽  
C. Psarropoulou ◽  
V. Tancredi ◽  
Y. Fueta
Keyword(s):  
Nmda Receptor ◽  
Gabaa Receptor ◽  
Action Potentials ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Occurrence Rate ◽  
Gamma Aminobutyric Acid ◽  
Synchronous Activity ◽  
Ca3 Pyramidal Cells

1. Extracellular field potential and intracellular recordings were made in the CA3 subfield of hippocampal slices obtained from 10- to 24-day-old rats during perfusion with artificial cerebrospinal fluid (ACSF) containing the convulsant 4-aminopyridine (4-AP, 50 microM). 2. Three types of spontaneous, synchronous activity were recorded in the presence of 4-AP by employing extracellular microelectrodes positioned in the CA3 stratum (s.) radiatum: first, inter-ictal-like discharges that lasted 0.2-1.2 s and had an occurrence rate of 0.3-1.3 Hz; second, ictal-like events (duration: 3-40 s) that occurred at 4-38 x 10(-3) Hz; and third, large-amplitude (up to 8 mV) negative-going potentials that preceded the onset of the ictal-like events and thus appeared to initiate them. 3. None of these synchronous activities was consistently modified by addition of antagonists of the N-methyl-D-aspartate (NMDA) receptor to the ACSF. In contrast, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 2-10 microM) reversibly blocked interictal- and ictallike discharges. The only synchronous, spontaneous activity recorded in this type of medium consisted of the negative-going potentials that were abolished by the GABAA receptor antagonists bicuculline methiodide (5-20 microM) or picrotoxin (50 microM). Hence they were mediated through the activation of the GABAA receptor. 4. Profile analysis of the 4-AP-induced synchronous activity revealed that the gamma-aminobutyric acid (GABA)-mediated field potential had maximal negative amplitude in s. lacunosum-moleculare, attained equipotentiality at the border between s. radiatum and s. pyramidale, and became positive-going in s. oriens. These findings indicated that the GABA-mediated field potential presumably represented a depolarization occurring in the dendrites of CA3 pyramidal cells. 5. This conclusion was supported by intracellular analysis of the 4-AP-induced activity. The GABA-mediated potential was reflected by a depolarization of the membrane of CA3 pyramidal cells that triggered a few variable-amplitude, fractionated spikes or fast action potentials. By contrast, the ictal-like discharge was associated with a prolonged depolarization during which repetitive bursts of action potentials occurred. Short-lasting depolarizations with bursts of action potentials occurred during each interictal-like discharge. 6. The GABA-mediated potential recorded intracellularly in the presence of CNQX consisted of a prolonged depolarization (up to 12 s) that was still capable of triggering a few fast action potentials and/or fractionated spikes.(ABSTRACT TRUNCATED AT 400 WORDS)

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