Nonsynaptic epileptogenesis in the mammalian hippocampus in vitro. I. Development of seizurelike activity in low extracellular calcium

1986 ◽  
Vol 56 (2) ◽  
pp. 409-423 ◽  
Author(s):  
A. Konnerth ◽  
U. Heinemann ◽  
Y. Yaari
Keyword(s):  
Epileptiform Activity ◽  
Large Population ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Discharge Zone ◽  
Critical Threshold ◽  
Mean Velocity ◽  
Stratum Pyramidale ◽  
Ca1 Area

Epileptiform activity induced in rat hippocampal slices by lowering extracellular Ca2+ concentration ([Ca2+]o) was studied with extracellular and intracellular recordings. Perfusing the slices with low Ca2+ (less than or equal to 0.2 mM) or EGTA-containing solutions blocked the synaptic responses of hippocampal pyramidal cells (HPCs). Despite the block, spontaneous paroxysms, termed seizurelike events (SLEs), appeared in the CA1 area and then recurred regularly at a stable frequency. Transient hypoxia accelerated their development and increased their frequency. When [Ca2+]o was raised in a stepwise manner, the SLEs disappeared at 0.3 mM. With extracellular recording from the CA1 stratum pyramidale, a SLE was characterized by a large negative shift in the field potential, which lasted for several seconds. During this period a large population of CA1 neurons discharged intensely and often in synchrony, as concluded from the frequent appearance of population spikes. Synchronization, however, was not a necessary precursor for the development of paroxysmal activity, but seemed to be the end result of massive neuronal excitation. The cellular counterpart of a SLE, as revealed by intracellular recording from HPCs in the discharge zone of the paroxysms, was a long-lasting depolarization shift (LDS) of up to 20 mV. This was accompanied by accelerated firing of the neuron. A prolonged after-hyperpolarization succeeded each LDS and arrested cell firing. Brief (approximately 50 ms) bursts were commonly observed before LDS onset. Single electrical stimuli applied focally to the stratum pyramidale or alveus evoked paroxysms identical to the spontaneous SLEs, provided they surpassed a critical threshold intensity. Subthreshold stimuli elicited only small local responses, whereas stimuli of varied suprathreshold intensities evoked the same maximal SLEs. Thus the buildup of a SLE is an all or nothing or a regenerative process, which mobilizes the majority, if not all, of the local neuronal population. Each SLE was followed by absolute and relative refractory periods during which focal stimulation was, respectively, ineffective and less effective in evoking a maximal SLE. In most slices the spontaneous SLEs commenced at a "focus" located in the CA1a subarea (near the subiculum). SLEs evoked by focal stimulation arose near the stimulating electrode. From their site of origin the paroxysmal discharges spread transversely through the entire CA1 area at a mean velocity of 1.74 mm/s. Consequently, the discharge zone of a SLE could encompass for several seconds the entire CA1 area.(ABSTRACT TRUNCATED AT 400 WORDS)

Extracellular Chloride and the Maintenance of Spontaneous Epileptiform Activity in Rat Hippocampal Slices

1999 ◽  
Vol 81 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Daryl W. Hochman ◽  
Raimondo D'Ambrosio ◽  
Damir Janigro ◽  
Philip A. Schwartzkroin
Keyword(s):  
Prolonged Exposure ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Spontaneous Discharge ◽  
Extracellular Potassium ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Region ◽  
Negative Field

Hochman, Daryl W., Raimondo D'Ambrosio, Damir Janigro, and Philip A. Schwartzkroin. Extracellular chloride and the maintenance of spontaneous epileptiform activity in rat hippocampal slices. J. Neurophysiol. 81: 49–59, 1999. Previous studies showed that furosemide blocks spontaneous epileptiform activity without diminishing synaptic transmission or reducing hyperexcited field responses to electrical stimuli. We now test the hypothesis that the antiepileptic effects of furosemide are mediated through its blockade of the Na+,K+,2Cl− cotransporter and thus should be mimicked by a reduction of extracellular chloride ([Cl−]o). In the first set of experiments, field recordings from the CA1 cell body layer of hippocampal slices showed that spontaneous bursting developed within 10–20 min in slices perfused with low-[Cl−]o (7 mM) medium but that this spontaneous epileptiform activity ceased after a further 10–20 min. Intracellular recordings from CA1 pyramidal cells showed that normal action potential discharge could be elicited by membrane depolarization, even after the tissue was perfused with low-[Cl−]o medium for >2 h. In a second set of experiments, spontaneous bursting activity was induced in slices by perfusion with high-[K+]o (10 mM), bicuculline (100 μM), or 4-aminopyridine (100 μM). In each case, recordings from the CA1 region showed that reduction of [Cl−]o to 21 mM reversibly blocked the bursting within 1 h. Similar to previous observations with furosemide treatment, low-[Cl−]o medium blocked spontaneous hypersynchronous discharges without reducing synaptic hyperexcitability (i.e., hyperexcitable field responses evoked by electrical stimulation). In a third set of experiments, prolonged exposure (>1 h after spontaneous bursting ceased) of slices to systematically varied [Cl−]o and [K+]o resulted in one of three types of events: 1) spontaneous, long-lasting, and repetitive negative field potential shifts (7 mM [Cl−]o; 3 mM [K+]o); 2) oscillations consisting of 5- to 10-mV negative shifts in the field potential, with a period of ∼1 cycle/40 s (16 mM [Cl−]o; 12 mM [K+]o); and 3) shorter, infrequently occurring negative field shifts lasting 20–40 s (21 mM [Cl−]o; 3 mM [K+]o). Our observations indicate that the effects of low [Cl−]o on neuronal synchronization and spontaneous discharge are time dependent. Similar effects were seen with furosemide and low [Cl−]o, consistent with the hypothesis that the antiepileptic effect of furosemide is mediated by the drug's effect on chloride transporters. Finally, the results of altering extracellular potassium along with chloride suggest that blockade of the Na+, K+,2Cl− cotransporter, which normally transports chloride from the extracellular space into glial cells, is key to these antiepileptic effects.

Changes in [K+]o evoked by baclofen in guinea pig hippocampus

1998 ◽  
Vol 76 (2) ◽  
pp. 148-154 ◽  
Author(s):  
G V Obrocea ◽  
Mary E Morris
Keyword(s):  
Guinea Pig ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Brain Slices ◽  
Field Potential ◽  
Stratum Radiatum ◽  
Extracellular Potassium ◽  
Receptor Subtype ◽  
Field Potentials ◽  
Stratum Pyramidale

K+-sensitive microelectrodes were used to record changes evoked by baclofen in extracellular potassium concentration ([K+]o) and field potentials in the stratum pyramidale (SP) and stratum radiatum (SR) in the CA1b region of guinea pig hippocampal slices in vitro. Bath applications of ( ±)-baclofen (1 µM - 3 mM for approx 5 min) evoked changes in [K+]o, which were in most cases sustained throughout agonist application and reversed during washout. The maximal (Rmax) values for curves fitted to the concentration-response data were for SP and SR, respectively, 0.59 ± 0.03 and 0.65 ± 0.03 mM, and EC50 values were 39.7 and 39.4 µM, respectively. The evoked K+ and field potential changes were significantly correlated and could be blocked by 2-OH-saclofen (50 µM) and CGP 35348 (50 µM). In <= 10% of experiments baclofen (10-50 µM) induced either a decrease or a transient increase ( <= 1 min duration) in [K+]o; in some slices with concentrations >=20 µM an initial decrease preceded a progressive increase. Pressure ejection of baclofen (100 µM for 100-900 ms) evoked increases in [K+]o and field potentials, which were larger in SR than in SP. In <= 10% of slices brief and (or) sustained application of baclofen (by either bath perfusion or pressure ejection) also evoked synchronous, repetitive interictal and ictal discharges at frequencies approx 1/s and 1/12 s, respectively, an observation that affirms a proconvulsant capacity. It is concluded that (i) although increases in [K+]o evoked by baclofen in SR compared with SP are slightly larger, they are not significantly different, (ii) GABAB receptor subtype(s) in SR and SP appear similar, as they have identical affinities, and (iii) [K+]o accumulations evoked by GABA likely include a contribution from a GABAB receptor activated K+ conductance, especially in dendritic regions.Key words: brain slices, stratum pyramidale, stratum radiatum, GABAB receptors, ion-selective microelectrodes, epileptiform activity.

Osmotic effects on the CA1 neuronal population in hippocampal slices with special reference to glucose

1991 ◽  
Vol 65 (5) ◽  
pp. 1055-1066 ◽  
Author(s):  
B. A. Ballyk ◽  
S. J. Quackenbush ◽  
R. D. Andrew
Keyword(s):  
Action Potential ◽  
Single Cell ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Stratum Radiatum ◽  
Resting Potential ◽  
Excitatory Postsynaptic Potential ◽  
Stratum Pyramidale ◽  
Postsynaptic Potential ◽  
Axonal Excitability

1. Lowered osmolality promotes epileptiform activity both clinically and in the hippocampal slice preparation, but it is unclear how neurons are excited. We studied the effects of altered osmolality on the electrophysiological properties of CA1 pyramidal cells in hippocampal slices by the use of field and intracellular recordings. The excitability of these neurons under various osmotic conditions was gauged by population spike (PS) amplitude, single cell properties, and evoked synaptic input. 2. The orthodromic PS recorded in stratum pyramidale and the field excitatory postsynaptic potential (EPSP) in stratum radiatum were inversely proportional in amplitude to the artificial cerebrospinal fluid (ACSF) osmolality over a range of +/- 80 milliosmoles/kgH2O (mosM). The effect was osmotic because changes occurred within the time frame expected for cellular expansion or shrinkage and because permeable substances such as dimethyl sulfoxide or glycerol were without effect. Dilutional changes in ACSF constituents were experimentally ruled out as promoting excitability. 3. To test whether the field data resulted from a change in single-cell excitability, CA1 cells were intracellularly recorded during exposure to +/- 40 mosM ACSF over 15 min. There was no consistent effect upon CA1 resting potential, cell input resistance, or action potential threshold. 4. Osmotic alteration of orthodromic and antidromic field potentials might involve a change in axonal excitability. However, the evoked afferent volley recorded in CA1 stratum pyramidale or radiatum, which represents the compound action potential (CAP) generated in presynaptic axons, remained osmotically unresponsive with regard to amplitude, duration, or latency. This was also characteristic of CAPs evoked in isolated sciatic and vagus nerve preparations exposed to +/- 80 mosM. Therefore axonal excitability and associated extracellular current flow generated periaxonally are not significantly affected by osmotic shifts. 5. The osmotic effect on field potential amplitudes appeared to be independent of synaptic transmission because the inverse relationship with osmolality held for the antidromically evoked PS. Moreover, as recorded with respect to ground, the intracellular EPSP-inhibitory postsynaptic potential (IPSP) sequence (evoked from CA3 stratum radiatum) was not altered by osmolality. 6. The PS could occasionally be recorded intracellularly as a brief negativity interrupting the evoked EPSP. In hyposmotic ACSF, the amplitude increased and action potentials arose from the trough of the negativity as expected for a field effect. This is presumably the result of enhanced intracellular channeling of current caused by the increased extracellular resistance that accompanies cellular swelling.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrophysiological evidence from glutamate microapplications for local excitatory circuits in the CA1 area of rat hippocampal slices

1988 ◽  
Vol 59 (1) ◽  
pp. 110-123 ◽  
Author(s):  
E. P. Christian ◽  
F. E. Dudek
Keyword(s):  
Hippocampal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Inhibitory Synapses ◽  
Excitatory Synapses ◽  
Recording Site ◽  
Postsynaptic Potentials ◽  
Inhibitory Postsynaptic Potentials ◽  
Ca1 Area ◽  
Transverse Slice

1. Evidence for local excitatory synaptic connections in CA1 of the rat hippocampus was obtained by recording excitatory postsynaptic potentials (EPSPs) intracellularly from pyramidal cells during local microapplications of glutamate. 2. Experiments were performed in hippocampal slices cut parallel to (transverse slice) or perpendicular to (longitudinal slice) alvear fibers. In normal solutions, glutamate microdrops (10–20 mM, 10–20 micron diam) applied in CA1 within 400 micron of recorded cells sometimes increased the frequency of inhibitory postsynaptic potentials for 5–10 s in both transverse and longitudinal slices. Increases in EPSP frequency were also occasionally observed, but only in transverse slices. Tetrodotoxin (1 microgram/ml) blocked glutamate-induced increases in PSP frequency, thus indicating that they were not caused by subthreshold effects on presynaptic terminals. Increases in PSP frequency were interpreted to result from glutamate activation of hippocampal neurons with inhibitory and excitatory connections to recorded neurons. 3. In both slice orientations, local excitatory circuits were studied in more isolated conditions by surgically separating CA1 from CA3 (transverse slices) and by blocking GABAergic inhibitory synapses with picrotoxin (5–10 microM). Microdrops were systematically applied at 200 and 400 micron on each side of the recording site. Significant glutamate-induced increases in EPSP frequency were observed in neurons from both slice orientations to microdrops in at least one of the locations. This provided evidence that excitatory synapses are present in both transverse and longitudinal slices. 4. Substantial increases in EPSP frequency only occurred in neurons from longitudinal slices when glutamate was microapplied 200 micron or less from the recording site. In transverse slices, however, large increases in EPSP frequency were observed to glutamate microapplications at 200 or 400 micron. These data suggest that CA1 local excitatory connections project for longer distances in the transverse than in the longitudinal plane of section. 5. Increases in EPSP frequency, averaged across cells, did not differ significantly in the four microapplication sites in either transverse or longitudinal slices. Thus local excitation in CA1 does not appear to be asymmetrically arranged in the way suggested for CA3. 6. The densities of local excitatory circuits in CA1 versus CA3 were studied by quantitatively comparing glutamate-induced increases in EPSP frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Epileptiform activity induced by low chloride medium in the CA1 subfield of the hippocampal slice

1990 ◽  
Vol 64 (6) ◽  
pp. 1747-1757 ◽  
Author(s):  
M. Avoli ◽  
C. Drapeau ◽  
P. Perreault ◽  
J. Louvel ◽  
R. Pumain
Keyword(s):  
Membrane Potential ◽  
Large Amplitude ◽  
Action Potentials ◽  
Hippocampal Slice ◽  
Epileptiform Activity ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Field Potentials ◽  
Maximal Amplitude

1. Extracellular and intracellular recordings and measurements of the extracellular concentration of free K+ ([K+]o) were performed in the CA1 subfield of the rat hippocampal slice during perfusion with artificial cerebrospinal fluid (ACSF) in which NaCl had been replaced with equimolar Na-isethionate or Na-methylsulfate (hereafter called low Cl- ACSF). 2. CAl pyramidal cells perfused with low Cl- ACSF generated intracellular epileptiform potentials in response to orthodromic, single-shock stimuli delivered in stratum (S.) radiatum. Low-intensity stimuli evoked a short-lasting epileptiform burst (SB) of action potentials that lasted 40–150 ms and was followed by a prolonged hyperpolarization. When the stimulus strength was increased, a long-lasting epileptiform burst (LB) appeared; it had a duration of 4–15 s and consisted of an early discharge of action potentials similar to the SB, followed by a prolonged, large-amplitude depolarizing plateau. The refractory period of the LB was longer than 20 s. SB and LB were also seen after stimulation of the alveus. 3. Variations of the membrane potential with injection of steady. DC current modified the shape of SB and LB. When microelectrodes filled with the lidocaine derivative QX-314 were used, the amplitudes of both SB and LB increased in a linear fashion during changes of the baseline membrane potential in the hyperpolarizing direction. The membrane input resistance, as measured by injecting brief square pulses of hyperpolarizing current, decreased by 65-80% during the long-lasting depolarizing plateau of LB. 4. A synchronous field potential and a transient increase in [K+]o accompanied the epileptiform responses. The extracellular counterpart of the SB was a burst of three to six population spikes and a small increase in [K+]o (less than or equal to 2 mM from a resting value of approximately 2.5 mM). The LB was associated with a large-amplitude, biphasic, negative field potential and a large increase in [K+]o (up to 12.4 mM above the resting value). Changes in [K+]o during the LB were largest at the border between S. oriens and S. pyramidale. This was also the site where the field potentials measured 2–5 s after the stimulus attained their maximal amplitude. Conversely, field potentials associated with the early component of the LB or with the SB displayed a maximal amplitude in the S. radiatum. 5. Spontaneous SBs and LBs were at times recorded in the CA1 and in the CA3 subfield.(ABSTRACT TRUNCATED AT 400 WORDS)

The dendritic origins of penicillin-induced epileptogenesis in CA3 hippocampal pyramidal cells

1986 ◽  
Vol 56 (6) ◽  
pp. 1718-1738 ◽  
Author(s):  
J. W. Swann ◽  
R. J. Brady ◽  
R. J. Friedman ◽  
E. J. Smith
Keyword(s):  
Cell Body ◽  
Average Distance ◽  
Hippocampal Slices ◽  
Current Source ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Large Current ◽  
Hippocampal Ca3 ◽  
Ca3 Pyramidal Cells ◽  
Negative Field

Experiments were performed in order to identify the sites of epileptiform burst generation in rat hippocampal CA3 pyramidal cells. A subsequent slow field potential was studied, which is associated with afterdischarge generation. Laminar field potential and current source-density (CSD) methods were employed in hippocampal slices exposed to penicillin. Simultaneous intracellular and extracellular field recordings from the CA3 pyramidal cell body layer showed that whenever an epileptiform burst was recorded extracellularly, individual CA3 neurons underwent an intense depolarization shift. In extracellular records a slow negative field potential invariably followed epileptiform burst generation. In approximately 10% of slices, synchronous afterdischarges rode on the envelope of this negative field potential. Intracellularly a depolarizing afterpotential followed the depolarization shift and was coincident with the extracellular slow negative field potential. A one-dimensional CSD analysis performed perpendicular to the CA3 cell body layer showed that during epileptiform burst generation large current sinks occur simultaneously in the central portions of both the apical and basilar dendrites. The average distance of the peak amplitude for these sinks from the center of the cell body layer was 175 +/- 46.8 microns and 158 +/- 25.0 microns, respectively. A large current source was recorded in the cell body layer. Smaller current sources were observed in the distal portions of the dendritic layers. During the postburst slow field potential a current sink was recorded at the edge of the cell body layer in stratum oriens--a region referred to as the infrapyramidal zone. Simultaneous with the current sink recorded there, smaller sinks were often observed in the dendritic layers that appeared to be "tails" or prolongations of the currents underlying burst generation. Two-dimensional analyses of these field potentials were performed on planes parallel and perpendicular to the exposed surface of the slice. Isopotential contours showed that the direction of extracellular current is mainly orthogonal to the CA3 laminae. Correction of CSD estimates made perpendicular to the cell body layer for current flowing in the other direction did not alter the location of computed current sources and sinks. In order to show that the dendritic currents associated with epileptiform burst generation were active sinks, tetrodotoxin (TTX) was applied locally to the dendrites where the current sinks were recorded.(ABSTRACT TRUNCATED AT 400 WORDS)

Synaptic Depolarizing GABA Response in Adults Is Excitatory and Proconvulsive When GABAB Receptors Are Blocked

2005 ◽  
Vol 93 (5) ◽  
pp. 2656-2667 ◽  
Author(s):  
Joshua T. Kantrowitz ◽  
N. Noelle Francis ◽  
Alejandro Salah ◽  
Katherine L. Perkins
Keyword(s):  
Voltage Clamp ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Phosphinic Acid ◽  
Pyramidal Cells ◽  
Cell Voltage ◽  
Gaba Release ◽  
Gabab Receptors ◽  
The Mean ◽  
Ca3 Pyramidal Cells

In the presence of 4-aminopyridine, interneurons fire synchronously, causing giant GABA-mediated postsynaptic potentials (GPSPs; GPSCs in voltage clamp) in CA3 pyramidal cells in hippocampal slices from adult guinea pigs. These triphasic GPSPs are composed of a GABAA-mediated hyperpolarizing component, a depolarizing component, and a GABAB-mediated hyperpolarizing component. We propose that GABAB receptors exert control over the postsynaptic depolarizing GABA response. Microelectrode and cell-attached recordings demonstrated that the mean number of action potentials during the depolarizing component of the GPSP increased dramatically in the presence of the GABAB receptor antagonist (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2- hydroxypropyl](phenylmethyl) phosphinic acid (CGP 55845A; P = 0.003 and 0.0005, respectively). Whole cell voltage-clamp recordings showed that the postsynaptic GABAB and depolarizing GABA components of the GPSC overlap substantially, allowing the GABAB-mediated hyperpolarization to suppress the excitation mediated by the depolarizing GABA component. Further voltage-clamp recordings showed that CGP 55845A increased the duration of the depolarizing GABA component of the GPSC even when the GABAB component had already been blocked by internal QX-314, suggesting that CGP 55845A also increased the duration of GABA release. When glutamatergic transmission is intact, GPSPs directly precede epileptiform afterdischarges. We hypothesize that the depolarizing component of the GPSP triggers the epileptiform events and show here that enhancement of the depolarizing component with CGP 55845A increased epileptiform activity. CGP 55845A increased the likelihood of a GPSP triggering an epileptiform event from 32 to 99% ( P = 0.0000001), and significantly increased the number of afterdischarges per epileptiform event ( P = 0.001). Loss of GABAB receptor function is associated with temporal lobe epilepsy in rodents and humans. We show here that GABAB receptors exert control over the synaptic depolarizing GABA response and that block of GABAB receptors makes the depolarizing GABA response excitatory and proconvulsive.

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)

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.

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