Hippocampal inhibitory interneurons are functionally disconnected from excitatory inputs by anoxia

1993 ◽  
Vol 70 (6) ◽  
pp. 2251-2259 ◽  
Author(s):  
R. Khazipov ◽  
P. Bregestovski ◽  
Y. Ben-Ari
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Gabab Receptors ◽  
Stratum Radiatum ◽  
Gamma Aminobutyric Acid ◽  
Patch Clamp Recording ◽  
Synaptic Currents ◽  
Postsynaptic Currents ◽  
Whole Cell Patch Clamp

1. The effects of anoxia on inhibitory synaptic transmission were studied in hippocampal slices of 3- to 4-wk-old rats. CA1 pyramidal cells were examined by whole-cell patch-clamp recording. Synaptic currents were evoked by “distant” (> 0.5 mm) or “close” (< 0.5 mm) electrical stimulation in the stratum radiatum. 2. The excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs) evoked by distant stimulation were completely suppressed by brief anoxia (95% N2-5% CO2 for 4-6 min) and recovered upon reoxygenation. IPSCs were more sensitive to anoxia than EPSCs. EPSCs and IPSCs evoked by distant stimulation were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM) and D-2-amino-5-phosphonopentanoate (APV; 50 microM). This indicates that IPSCs were mediated via a polysynaptic pathway that involves glutamate receptors. 3. Synaptic currents evoked by close stimulation were only partly inhibited by anoxia. The bicuculline-sensitive gamma-aminobutyric acid-A (GABAA) receptor-mediated synaptic currents were particularly resistant to anoxia, suggesting that the GABAergic input to pyramidal neurons is not inhibited by anoxia. 4. At close stimulation in the stratum radiatum, monosynaptic IPSCs could be evoked in the presence of CNQX (20 microM) and APV (50 microM). The monosynaptic IPSCs had early bicuculline (15 microM) and late CGP 35348 (100 microM)-sensitive components confirming an involvement of GABAA and GABAB receptors (IPSCA and IPSCB components), respectively. 5. The monosynaptic IPSCA component evoked by close stimulation was not changed significantly during and after brief anoxia. Responses to pressure application of isoguvacine (GABAA agonist) were also not affected by anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Agent-selective Effects of Volatile Anesthetics on GABAAReceptor–mediated Synaptic Inhibition in Hippocampal Interneurons

2001 ◽  
Vol 94 (2) ◽  
pp. 340-347 ◽  
Author(s):  
Koichi Nishikawa ◽  
M. Bruce MacIver
Keyword(s):  
Gabaa Receptor ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Volatile Anesthetics ◽  
Stratum Radiatum ◽  
Synaptic Inhibition ◽  
Gamma Aminobutyric Acid ◽  
Ca1 Region ◽  
Whole Cell Patch Clamp ◽  
Cortical Regions

Background A relatively small number of inhibitory interneurons can control the excitability and synchronization of large numbers of pyramidal cells in hippocampus and other cortical regions. Thus, anesthetic modulation of interneurons could play an important role for the maintenance of anesthesia. The aim of this study was to compare effects produced by volatile anesthetics on inhibitory postsynaptic currents (IPSCs) of rat hippocampal interneurons. Methods Pharmacologically isolated gamma-aminobutyric acid type A (GABAA) receptor-mediated IPSCs were recorded with whole cell patch-clamp techniques in visually identified interneurons of rat hippocampal slices. Neurons located in the stratum radiatum-lacunosum moleculare of the CA1 region were studied. The effects of clinically relevant concentrations (1.0 rat minimum alveolar concentration) of halothane, enflurane, isoflurane, and sevoflurane were compared on kinetics of both stimulus-evoked and spontaneous GABAA receptor-mediated IPSCs in interneurons. Results Halothane (1.2 vol% approximately 0.35 mm), enflurane (2.2 vol% approximately 0.60 mm), isoflurane (1.4 vol% approximately 0.50 mm), and sevoflurane (2.7 vol% approximately 0.40 mm) preferentially depressed evoked IPSC amplitudes to 79.8 +/- 9.3% of control (n = 5), 38.2 +/- 8.6% (n = 6), 52.4 +/- 8.4% (n = 5), and 46.1 +/- 16.0% (n = 8), respectively. In addition, all anesthetics differentially prolonged the decay time constant of evoked IPSCs to 290.1 +/- 33.2% of control, 423.6 +/- 47.1, 277.0 +/- 32.2, and 529 +/- 48.5%, respectively. The frequencies of spontaneous IPSCs were increased by all anesthetics (twofold to threefold). Thus, the total negative charge transfer mediated by GABAA receptors between synaptically connected interneurons was enhanced by all anesthetics. Conclusions Volatile anesthetics differentially enhanced GABAA receptor-mediated synaptic inhibition in rat hippocampal interneurons, suggesting that hippocampal interneuron circuits are depressed by these anesthetics in an agent-specific manner.

Presynaptic Inactivation of Action Potentials and Postsynaptic Inhibition of GABAA Currents Contribute to KA-Induced Disinhibition in CA1 Pyramidal Neurons

2004 ◽  
Vol 92 (2) ◽  
pp. 873-882 ◽  
Author(s):  
Ning Kang ◽  
Li Jiang ◽  
Wei He ◽  
Jun Xu ◽  
Maiken Nedergaard ◽  
...  
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Mean Amplitude ◽  
Stratum Radiatum ◽  
Depressant Effect ◽  
Patch Clamp Recording ◽  
Postsynaptic Inhibition ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents

Kainate-type glutamate ionotropic receptors (KAR) mediate either depression or potentiation of inhibitory transmission. The mechanisms underlying the depressant effect of KAR agonists have been controversial. Under dual patch-clamp recording techniques in synaptically coupled pairs of CA1 interneurons and pyramidal neurons in hippocampal slices, micromolar concentrations of KAR agonists, kainic acid (KA, 10 μM) and ATPA (10 μM), induced inactivation of action potentials (APs) in 58 and 50% of presynaptic interneurons, respectively. Inactivation of interneuronal APs might have significantly contributed to KA-induced decreases in evoked inhibitory postsynaptic currents (eIPSCs) that are obtained by stimulating the stratum radiatum. With controlled interneuronal APs, KAR agonists induced a decrease in the potency (mean amplitude of successful events) and mean amplitude (including failures) of unitary inhibitory postsynaptic currents (uIPSCs) without significantly changing the success rate (Ps) at perisomatic high-Ps synapses. In contrast, KAR agonists induced a decrease in both the Ps and potency of uIPSCs at dendritic high-Ps synapses. KAR agonists induced an inhibition of GABAA currents by activating postsynaptic KARs in pyramidal neurons; this was more prominent at dendrites than at soma. Both the exogenous GABA-induced current and the amplitude of miniature IPSCs (mIPSCs) were attenuated by KAR agonists. Thus the postsynaptic KAR-mediated inhibition of GABAA currents may contribute to the KAR agonist-induced decrease in the potency of uIPSCs and KA-induced disinhibition.

Direct demonstration of functional disconnection by anoxia of inhibitory interneurons from excitatory inputs in rat hippocampus

1995 ◽  
Vol 73 (1) ◽  
pp. 421-426 ◽  
Author(s):  
P. Congar ◽  
R. Khazipov ◽  
Y. Ben-Ari
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
Patch Clamp Technique ◽  
Ca1 Region ◽  
Whole Cell Patch Clamp ◽  
Direct Demonstration ◽  
Outward Currents

1. We studied the effects of anoxia on excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) evoked by electrical stimulation in the stratum radiatum in concomitantly recorded pyramidal cells and interneurons of the CA1 region of rat hippocampal slices. We used the blind whole cell patch-clamp technique, and anoxia was induced by switching perfusion of the slice from oxygenated artificial cerebral spinal fluid (ACSF) to ACSF saturated with 95% N2-5% CO2 for 4-6 min. 2. As in pyramidal neurons, anoxia induced in interneurons outward currents, during and shortly after the anoxic episode. Both currents were, however, significantly larger in interneurons than in pyramidal neurons. 3. EPSCs are more rapidly depressed by anoxia in interneurons than in simultaneously recorded pyramidal cells. 4. In pyramidal neurons, polysynaptic IPSCs (pIPSCs) evoked by conventional distant stimulation (> 1 mm) are more sensitive to anoxia then EPSCs. In contrast, in interneurons, anoxia blocks with a similar latency EPSCs and polysynaptic IPSCs. 5. To determine whether this block of pIPSCs in pyramidal cells is due to a shift in driving force or a change in conductance, we examined the current (I/V) relationships. The block by anoxia of pIPSCs is due to a reduction of IPSC conductance (> 98%) that occlude other events including the shift of IPSCs reversal potential (ECl).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Evidence of calcium-permeable AMPA receptors in dendritic spines of CA1 pyramidal neurons

2014 ◽  
Vol 112 (2) ◽  
pp. 263-275 ◽  
Author(s):  
Hayley A. Mattison ◽  
Ashish A. Bagal ◽  
Michael Mohammadi ◽  
Nisha S. Pulimood ◽  
Christian G. Reich ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Ampa Receptors ◽  
Pyramidal Neurons ◽  
Calcium Influx ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
Acute Hippocampal Slices ◽  
Cultured Slices ◽  
Apical Dendrites

GluA2-lacking, calcium-permeable α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPARs) have unique properties, but their presence at excitatory synapses in pyramidal cells is controversial. We have tested certain predictions of the model that such receptors are present in CA1 cells and show here that the polyamine spermine, but not philanthotoxin, causes use-dependent inhibition of synaptically evoked excitatory responses in stratum radiatum, but not s. oriens, in cultured and acute hippocampal slices. Stimulation of single dendritic spines by photolytic release of caged glutamate induced an N-methyl-d-aspartate receptor-independent, use- and spermine-sensitive calcium influx only at apical spines in cultured slices. Bath application of glutamate also triggered a spermine-sensitive influx of cobalt into CA1 cell dendrites in s. radiatum. Responses of single apical, but not basal, spines to photostimulation displayed prominent paired-pulse facilitation (PPF) consistent with use-dependent relief of cytoplasmic polyamine block. Responses at apical dendrites were diminished, and PPF was increased, by spermine. Intracellular application of pep2m, which inhibits recycling of GluA2-containing AMPARs, reduced apical spine responses and increased PPF. We conclude that some calcium-permeable, polyamine-sensitive AMPARs, perhaps lacking GluA2 subunits, are present at synapses on apical dendrites of CA1 pyramidal cells, which may allow distinct forms of synaptic plasticity and computation at different sets of excitatory inputs.

scholarly journals Progesterone Withdrawal Reduces Paired-Pulse Inhibition in Rat Hippocampus: Dependence on GABAA Receptor α4 Subunit Upregulation

2003 ◽  
Vol 89 (1) ◽  
pp. 186-198 ◽  
Author(s):  
Fu-Chun Hsu ◽  
Sheryl S. Smith
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Extracellular Recording ◽  
Pyramidal Cells ◽  
Chronic Administration ◽  
Female Rats ◽  
Stratum Radiatum ◽  
Intraventricular Administration ◽  
Paired Pulse ◽  
Ca1 Region

Withdrawal from the endogenous steroid progesterone (P) after chronic administration increases anxiety and seizure susceptibility via declining levels of its potent GABA-modulatory metabolite 3α-OH-5α-pregnan-20-one (3α,5αTHP). This 3α,5α-THP withdrawal also results in a decreased decay time constant for GABA-gated current assessed using whole cell patch-clamp techniques on pyramidal cells acutely dissociated from CA1 hippocampus. The purpose of this study was to test the hypothesis that the decreases in total integrated GABA-gated current observed at the level of the isolated pyramidal cell would be manifested as a reduced GABA inhibition at the circuit level following hormone withdrawal. Toward this end, adult, female rats were administered P via subcutaneous capsule for 3 wk using a multiple withdrawal paradigm. We then evaluated paired-pulse inhibition (PPI) of pyramidal neurons in CA1 hippocampus using extracellular recording techniques in hippocampal slices from rats 24 h after removal of the capsule (P withdrawal, P Wd). The population spike (PS) was recorded at the stratum pyramidale following homosynaptic orthodromic stimulation in the nearby stratum radiatum. The threshold for eliciting a response was decreased after P Wd, and the mean PS amplitude was significantly increased compared with control values at this time. Paired pulses with 10-ms inter-pulse intervals were then applied across an intensity range from 2 to 20 times threshold. Evaluation of paired-pulse responses showed a significant 40–50% reduction in PPI for PS recorded in the hippocampal CA1 region after P Wd, suggesting an increase in circuit excitability. At this time, enhancement of PPI by the benzodiazepine lorazepam (LZM; 10 μM) was prevented, while pentobarbital (10 μM) potentiation of PPI was comparable to control levels of response. These data are consistent with upregulation of the α4 subunit of the GABAA receptor (GABAR) as we have previously shown. Moreover, the reduced PPI caused by P Wd was prevented by suppression of GABAR α4-subunit expression following intraventricular administration of specific antisense oligonucleotides (1 μg/h for 72 h). These results demonstrating a reduction in PPI following P Wd suggest that GABAergic-mediated recurrent or feed-forward inhibition occurring at the circuit level were decreased following P Wd in female rats, an effect at least partially attributable to alterations in the GABAR subunit gene expression.

The uptake inhibitor L-trans-PDC enhances responses to glutamate but fails to alter the kinetics of excitatory synaptic currents in the hippocampus

1993 ◽  
Vol 70 (5) ◽  
pp. 2187-2191 ◽  
Author(s):  
J. S. Isaacson ◽  
R. A. Nicoll
Keyword(s):  
Time Course ◽  
Glutamate Uptake ◽  
Hippocampal Slices ◽  
Synaptic Cleft ◽  
Gamma Aminobutyric Acid ◽  
Patch Clamp Recording ◽  
Glutamatergic Synapses ◽  
Synaptic Currents ◽  
Ca1 Region ◽  
Transmitter Uptake

1. We have used patch-clamp recording techniques to study the physiological properties of a recently described glutamate uptake blocker, L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC), in the CA1 region of the guinea pig hippocampus. 2. L-trans-PDC markedly potentiated the action of exogenously applied glutamate and raised the ambient extracellular levels of glutamate in hippocampal slices. Despite these actions, L-trans-PDC did not affect the time course of either the N-methyl-D-aspartate (NMDA) or non-NMDA receptor-mediated synaptic currents evoked by the stimulation of a large number of neighboring synapses. 3. These findings are consistent with models of fast synaptic transmission in which transmitter is rapidly cleared from the synaptic cleft by diffusion. However, in marked contrast to fast gamma-aminobutyric acid A (GABAA) synapses in the hippocampus, uptake does not appear to play a role in regulating the "spill-over" of transmitter from neighboring, co-activated glutamatergic synapses. Therefore, either diffusion alone can effectively limit the temporal and spatial domain of synaptically released glutamate, or alternatively, L-trans-PDC like other currently available blockers is not sufficiently potent to reveal a role for transmitter uptake at glutamatergic synapses.

Spontaneous and stimulation-induced synchronized burst afterdischarges in the isolated CA1 of kainate-treated rats

1996 ◽  
Vol 76 (4) ◽  
pp. 2231-2239 ◽  
Author(s):  
C. L. Meier ◽  
F. E. Dudek
Keyword(s):  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
Maximal Response ◽  
Gamma Aminobutyric Acid ◽  
Population Spikes ◽  
Ca3 Pyramidal Cells ◽  
Ca1 Area ◽  
Hilar Neurons ◽  
Area Ca3

1. Kainate treatment preferentially kills dentate hilar neurons and CA3 pyramidal cells and ultimately leads to a chronic epileptic state. Bicuculline-induced epileptiform bursts were studied to test the hypothesis that multiple kainate injections and consequent status epilepticus would lead-after weeks to months of recovery-to prolonged synchronous afterdischarges in the isolated CA1 area of rat hippocampal slices, as would be expected if new recurrent excitatory circuits had formed. 2. Synaptic responses evoked in CA1 pyramidal cells of rats injected subcutaneously with kainate (10 hourly injections, 5 mg/kg each) 24-316 days before the slice experiment were compared with responses in slices from untreated and saline-injected controls. The maximal response to stratum radiatum stimulation in normal solution consisted of two to eight population spikes. 3. When gamma-aminobutyric acid-A receptor-mediated inhibition was reduced with bicuculline, synchronized burst afterdischarges after the initial stimulation-evoked burst, similar to the type of activity described in area CA3 under conditions where inhibition is impaired, occurred in 23% of slices. 4. The prolonged synchronized burst afterdischarges in the isolated CA1 area of kainate-treated rats were associated with large excitatory postsynaptic potentials (EPSPs). These prolonged bursts were not graded with the stimulus intensity; rather, they were triggered in an all-or-none manner, even though there was some variability across bursts. The bursts of population spikes also were correlated with subthreshold EPSPs. 5. Slices that had synchronized burst afterdischarges had significantly more damage in area CA3 than slices without afterdischarges. 6. The data indicate that kainate-induced damage in CA3 can lead to prolonged synchronous afterdischarges, even after CA1 is surgically isolated from the CA3 area. Because the repetitive bursts during the prolonged and synchronous afterdischarges were associated with large EPSPs, these data suggest that kainate-induced damage to CA3 and subsequent degeneration of synaptic terminals in the CA1 area causes the formation of new recurrent excitatory circuits that could be involved in the development of chronic epilepsy.

Electrophysiological Characterization of “Giant” Cells in Stratum Radiatum of the CA3 Hippocampal Region

2001 ◽  
Vol 85 (5) ◽  
pp. 1998-2007 ◽  
Author(s):  
Nataša Savić ◽  
Marina Sciancalepore
Keyword(s):  
Glutamate Receptor ◽  
Action Potentials ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Giant Cells ◽  
Stratum Radiatum ◽  
Patch Clamp Recording ◽  
Postsynaptic Currents ◽  
Electrophysiological Characterization

Whole cell patch-clamp recording and intracellular staining with biocytin allowed the morphological and electrophysiological characterization of “giant” cells, studied in stratum (st.) radiatum of the CA3 region in 17- to 21-day-old rat hippocampal slices. These neurons had extensive dendritic arborization, a triangular soma, and a bipolar vertical orientation with axons directed to the pyramidal layer or extended into the st. oriens. Giant cells had significantly higher input resistance and shorter action potentials compared with CA3 pyramidal cells. Evoked action potentials were typically followed by an afterdepolarizing potential (ADP). During depolarizing current injection, most (80%) of recorded giant cells displayed a regular firing pattern (maximum steady-state firing rate, ∼30 Hz) characterized by a modest early accommodation, whereas irregular firing was observed in the remaining 20% of giant cells. Hyperpolarizing current pulses induced a slow inward rectification of the electrotonic voltage responses, blocked by 2 mM external Cs+. N-methyl-d-aspartate (NMDA) and non-NMDA–mediated excitatory postsynaptic currents (EPSCs) measured under voltage clamp were distinguished on the basis of their voltage dependence and sensitivity to specific NMDA and non-NMDA glutamate receptor blockers. Non-NMDA EPSCs possessed a linear current-voltage relationship. EPSCs elicited by st. lucidum stimulation were reversibly reduced (mean, 23%) by the group II metabotropic glutamate receptor agonist (2S, 1′R, 2′R, 3′R)-2-(2,3-dicarboxyl-cyclopropyl)-glycine (DCG-IV, 1 μM). GABAA-mediated postsynaptic currents were subject to paired-pulse depression that was inhibited by the GABAB antagonist CGP 55845A (5 μM). We conclude that CA3 giant cells represent a particular class of hippocampal neuron located in st. radiatum that shares only some morphological and physiological properties with principal cells.

Posttetanic Excitation Mediated by GABAA Receptors in Rat CA1 Pyramidal Neurons

1997 ◽  
Vol 77 (4) ◽  
pp. 2213-2218 ◽  
Author(s):  
Tomi Taira ◽  
Karri Lamsa ◽  
Kai Kaila
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Neuronal Firing ◽  
Stratum Radiatum ◽  
Tetanic Stimulation ◽  
Glutamate Antagonists ◽  
Ca1 Pyramidal Neurons ◽  
Spike Firing

Taira, Tomi, Karri Lamsa, and Kai Kaila. Posttetanic excitation mediated by GABAA receptors in rat CA1 pyramidal neurons. J.Neurophysiol. 77: 2213–2218, 1997. The contributions of γ-aminobutyric acid (GABA) receptors to posttetanic excitation of CA1 pyramidal neurons in rat hippocampal slices were studied using extracellular and intracellular recording techniques. Synaptic responses were evoked on tetanic stimulation (100–200 Hz, 40–100 pulses) applied in stratum radiatum close (300–600 μm) to the recording site. Under control conditions, tetanic stimulation resulted in a triphasic depolarization/hyperpolarization/sustained depolarization sequence in area CA1 pyramidal cells. The late depolarization usually gave rise to a prolonged (≤3 s) spike firing. The late depolarization and the associated spike firing were blocked both specifically and completely (within a time window of 3–6 min starting from picrotoxin application) by the GABAA receptor antagonist picrotoxin (PiTX, 100 μM). Paradoxically, at this early stage of PiTX application, overall neuronal firing was attenuated to a higher degree than what was achieved by ionotropic glutamate antagonists. Complete block of ionotropic glutamate receptors by the antagonists d-2-amino-5-phosphonopentoate (AP5, 80 μM), 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX, 10 μM), and ketamine (50 μM) blocked the initial fast depolarization and suppressed the late one. Exposure to a permeable inhibitor of carbonic anhydrase, ethoxyzolamide (EZA, 50 μM) inhibited the late, apparently GABA-mediated depolarization. It is concluded that GABA can provide the main posttetanic excitatory drive in the adult hippocampus. The present results suggest that intense activation of GABAergic interneurons may accentuate the excitation of principal neurons and, hence, play an important facilitatory role in the induction of long-term potentiation (LTP) and epileptogenesis.

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