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.

The involvement of nonspiking cells in long-term potentiation of synaptic transmission in the hippocampus

1988 ◽  
Vol 66 (6) ◽  
pp. 841-844 ◽  
Author(s):  
B. R. Sastry ◽  
J. W. Goh ◽  
P. B. Y. May ◽  
S. S. Chirwa
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Stratum Radiatum ◽  
Ca1 Pyramidal Neurons ◽  
Term Potentiation ◽  
Ca1 Area ◽  
Glial Depolarization ◽  
Stimulation Of

In guinea pig hippocampal slices, stimulation of stratum radiatum during depolarization (with intracellular current injections) of nonspiking cells (presumed to be glia) in the apical dendritic area of CA1 pyramidal neurons resulted in a subsequent long-term potentiation of intracellularly recorded excitatory postsynaptic potentials as well as extracellularly recorded population spikes in the CA1 area. Tetanic stimulation of stratum radiatum resulted in a subsequent prolonged depolarization of the presumed glial cells, and this depolarization was smaller when the tetanus was given during the presence of 2-amino-5-phosphonovalerate or when the slices were exposed to Ca2+-free medium containing Mn2+ and Mg2+. These results suggest that glial depolarization is involved as one of the steps in generating long-term potentiation.

Group I mGluRs Increase Excitability of Hippocampal CA1 Pyramidal Neurons by a PLC-Independent Mechanism

2002 ◽  
Vol 88 (1) ◽  
pp. 107-116 ◽  
Author(s):  
David R. Ireland ◽  
Wickliffe C. Abraham
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Receptor Subtypes ◽  
Ca1 Pyramidal Neurons ◽  
Group I ◽  
Hippocampal Ca1 ◽  
Group I Mglurs ◽  
Induced Changes

Previous studies have implicated phospholipase C (PLC)-linked Group I metabotropic glutamate receptors (mGluRs) in regulating the excitability of hippocampal CA1 pyramidal neurons. We used intracellular recordings from rat hippocampal slices and specific antagonists to examine in more detail the mGluR receptor subtypes and signal transduction mechanisms underlying this effect. Application of the Group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) suppressed slow- and medium-duration afterhyperpolarizations (s- and mAHP) and caused a consequent increase in cell excitability as well as a depolarization of the membrane and an increase in input resistance. Interestingly, with the exception of the suppression of the mAHP, these effects were persistent, and in the case of the sAHP lasting for more than 1 h of drug washout. Preincubation with the specific mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), reduced but did not completely prevent the effects of DHPG. However, preincubation with both MPEP and the mGluR1 antagonist LY367385 completely prevented the DHPG-induced changes. These results demonstrate that the DHPG-induced changes are mediated partly by mGluR5 and partly by mGluR1. Because Group I mGluRs are linked to PLC via G-protein activation, we also investigated pathways downstream of PLC activation, using chelerythrine and cyclopiazonic acid to block protein kinase C (PKC) and inositol 1,4,5-trisphosphate-(IP3)-activated Ca2+ stores, respectively. Neither inhibitor affected the DHPG-induced suppression of the sAHP or the increase in excitability nor did an inhibitor of PLC itself, U-73122. Taken together, these results argue that in CA1 pyramidal cells in the adult rat, DHPG activates mGluRs of both the mGluR5 and mGluR1 subtypes, causing a long-lasting suppression of the sAHP and a consequent persistent increase in excitability via a PLC-, PKC-, and IP3-independent transduction pathway.

Threshold Conditions for Synaptically Evoking Ca2+Waves in Hippocampal Pyramidal Neurons

2002 ◽  
Vol 87 (4) ◽  
pp. 1799-1804 ◽  
Author(s):  
Suya Zhou ◽  
William N. Ross
Keyword(s):  
Pyramidal Neurons ◽  
Long Term Potentiation ◽  
Threshold Current ◽  
Lateral Position ◽  
Stratum Radiatum ◽  
Tetanic Stimulation ◽  
Hippocampal Pyramidal Neurons ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Stimulus Current

Regenerative Ca2+ release from inositol 1,4,5-trisphosphate (IP3)-sensitive intracellular stores in the form of Ca2+ waves leads to large-amplitude [Ca2+]iincreases in the apical dendrites of hippocampal CA1 pyramidal neurons. Release is generated following synaptic activation of group I metabotropic glutamate (mGlu) receptors. We systematically examined the conditions for evoking these waves in transverse slices from 2- to 3-wk-old rats. Using a sharpened asymmetrical bipolar tungsten stimulating electrode placed in the stratum radiatum, we varied the lateral position of the electrode, the number of stimulating pulses, the train frequency, and stimulus current. Several trends were clear. Increasing the frequency of stimulation from 20 to 100 Hz, keeping the total number of pulses constant, lowered the required stimulus current. Stimulation at frequencies below 20 Hz made it difficult to evoke release. Increasing the number of stimulation pulses, keeping the frequency constant, lowered the threshold current. A minimum of five pulses at 100 Hz was required to evoke release reliably, but several examples of success with three pulses were recorded. Theta-burst stimulation was as effective as tetanic stimulation. Placing the point of the stimulation electrode closer to the pyramidal neuron made it easier to evoke release, although stimulation at a lateral distance of 500 μm with unsharpened electrodes was sometimes successful. The simplest explanation for these results is that a bolus of IP3 must be produced quickly in a restricted region of the dendrites to generate Ca2+ waves. The conditions necessary for evoking regenerative Ca2+ release have many parallels (and some differences) with the conditions required to evoke long-term potentiation in these cells following tetanic stimulation.

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.

Inhibitory processes of hippocampal CA1 pyramidal neurons following kindling-induced epilepsy in the rat

1985 ◽  
Vol 63 (7) ◽  
pp. 872-878 ◽  
Author(s):  
M. W. Oliver ◽  
J. J. Miller
Keyword(s):  
Pyramidal Neurons ◽  
Epileptiform Activity ◽  
Pyramidal Cells ◽  
Repetitive Stimulation ◽  
Membrane Properties ◽  
Stratum Radiatum ◽  
Inhibitory Processes ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Stimulation Of

To determine the alterations in cellular function which may contribute to the chronic predisposition of neuronal tissue to epileptiform activity, the membrane properties and inhibitory processes of hippocampal CA1 pyramidal cells were investigated using in vitro slices prepared from commissural-kindled rats. No changes were observed in resting membrane potential, input resistance, spike amplitude, and membrane time constant of "kindled" CA1 pyramidal neurons when compared with controls. There were also no differences between control and kindled preparations in the amplitude of recurrent inhibitory postsynaptic potentials (IPSP) and in the duration of inhibition produced by either alvear (Alv) or stratum radiatum (SR) stimulation. Irrespective of group, repetitive stimulation of the Alv reduced the amplitude of the recurrent IPSP but failed to induce seizurelike activity. On the other hand, repetitive stimulation of SR frequently produced a neuronal burst discharge even though the duration and to some extent the amplitude of orthodromic inhibition was increased. On the basis of these data, it may be suggested that chronic changes in CA1 pyramidal cell membrane properties and transient reductions of inhibitory processes do not underlie the enhanced sensitivity of these neurons to seizure activity associated with kindling.

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.

2-Deoxyglucose–Induced Long-Term Potentiation in CA1 Is Not Prevented by Intraneuronal Chelator

2000 ◽  
Vol 83 (1) ◽  
pp. 177-180 ◽  
Author(s):  
Yong-Tao Zhao ◽  
Krešimir Krnjević
Keyword(s):  
Ethylene Glycol ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Stratum Radiatum ◽  
Tetanic Stimulation ◽  
Tetraacetic Acid ◽  
Ca1 Neurons ◽  
Term Potentiation ◽  
Stimulation Of

In hippocampal slices, temporary (10–20 min) replacement of glucose with 10 mM 2-deoxyglucose is followed by marked and very sustained potentiation of EPSPs (2-DG LTP). To investigate its mechanism, we examined 2-DG's effect in CA1 neurons recorded with sharp 3 M KCl electrodes containing a strong chelator, 50 or 100 mM ethylene glycol-bis(β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid (EGTA). In most cases, field EPSPs were simultaneously recorded and conventional LTP was also elicited in some cells by tetanic stimulation of stratum radiatum. 2-DG potentiated intracellular EPSP slopes by 48 ± 5.1% (SE) in nine cells recorded with plain KCl electrodes and by 52 ± 6.2% in seven cells recorded with EGTA-containing electrodes. In four of the latter cells, tetanic stimulation (twice 100 Hz for 1 s) failed to evoke LTP (2 ± 1.1%), although field EPSPs were clearly potentiated (by 28 ± 6.9%). Thus unlike tetanic LTP, 2-DG LTP is not readily prevented by postsynaptic intraneuronal injection of EGTA. These findings agree with other evidence that the rise in postsynaptic (somatic) [Ca2+]i caused by 2-DG is not the principal trigger for the subsequent 2-DG LTP and that it may be a purely presynaptic phenomenon.

scholarly journals TRPM4 Expression During Postnatal Developmental of Mouse CA1 Pyramidal Neurons

2021 ◽  
Vol 15 ◽  
Author(s):  
Denise Riquelme ◽  
Oscar Cerda ◽  
Elias Leiva-Salcedo
Keyword(s):  
Membrane Potential ◽  
Patch Clamp ◽  
Postnatal Development ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Long Term Potentiation ◽  
Neuronal Firing ◽  
Resting Membrane Potential ◽  
Ca1 Pyramidal Neurons ◽  
Apical Dendrites

TRPM4 is a non-selective cation channel activated by intracellular calcium and permeable to monovalent cations. This channel participates in the control of neuronal firing, neuronal plasticity, and neuronal death. TRPM4 depolarizes dendritic spines and is critical for the induction of NMDA receptor-dependent long-term potentiation in CA1 pyramidal neurons. Despite its functional importance, no subcellular localization or expression during postnatal development has been described in this area. To examine the localization and expression of TRPM4, we performed duplex immunofluorescence and patch-clamp in brain slices at different postnatal ages in C57BL/6J mice. At P0 we found TRPM4 is expressed with a somatic pattern. At P7, P14, and P35, TRPM4 expression extended from the soma to the apical dendrites but was excluded from the axon initial segment. Patch-clamp recordings showed a TRPM4-like current active at the resting membrane potential from P0, which increased throughout the postnatal development. This current was dependent on intracellular Ca2+ (ICAN) and sensitive to 9-phenanthrol (9-Ph). Inhibiting TRPM4 with 9-Ph hyperpolarized the membrane potential at P14 and P35, with no effect in earlier stages. Together, these results show that TRPM4 is expressed in CA1 pyramidal neurons in the soma and apical dendrites and associated with a TRPM4-like current, which depolarizes the neurons. The expression, localization, and function of TRPM4 throughout postnatal development in the CA1 hippocampal may underlie an important mechanism of control of membrane potential and action potential firing during critical periods of neuronal development, particularly during the establishment of circuits.

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)

Enhanced intrinsic excitability and EPSP-spike coupling accompany enriched environment-induced facilitation of LTP in hippocampal CA1 pyramidal neurons

2012 ◽  
Vol 107 (5) ◽  
pp. 1366-1378 ◽  
Author(s):  
Ruchi Malik ◽  
Sumantra Chattarji
Keyword(s):  
Environmental Enrichment ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Intrinsic Excitability ◽  
Excitatory Postsynaptic Potential ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
The Impact

Environmental enrichment (EE) is a well-established paradigm for studying naturally occurring changes in synaptic efficacy in the hippocampus that underlie experience-induced modulation of learning and memory in rodents. Earlier research on the effects of EE on hippocampal plasticity focused on long-term potentiation (LTP). Whereas many of these studies investigated changes in synaptic weight, little is known about potential contributions of neuronal excitability to EE-induced plasticity. Here, using whole-cell recordings in hippocampal slices, we address this gap by analyzing the impact of EE on both synaptic plasticity and intrinsic excitability of hippocampal CA1 pyramidal neurons. Consistent with earlier reports, EE increased contextual fear memory and dendritic spine density on CA1 cells. Furthermore, EE facilitated LTP at Schaffer collateral inputs to CA1 pyramidal neurons. Analysis of the underlying causes for enhanced LTP shows EE to increase the frequency but not amplitude of miniature excitatory postsynaptic currents. However, presynaptic release probability, assayed using paired-pulse ratios and use-dependent block of N-methyl-d-aspartate receptor currents, was not affected. Furthermore, CA1 neurons fired more action potentials (APs) in response to somatic depolarization, as well as during the induction of LTP. EE also reduced spiking threshold and after-hyperpolarization amplitude. Strikingly, this EE-induced increase in excitability caused the same-sized excitatory postsynaptic potential to fire more APs. Together, these findings suggest that EE may enhance the capacity for plasticity in CA1 neurons, not only by strengthening synapses but also by enhancing their efficacy to fire spikes—and the two combine to act as an effective substrate for amplifying LTP.

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