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.

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)

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.

scholarly journals Regulation of Inhibitory Synaptic Transmission by Vasoactive Intestinal Peptide (VIP) in the Mouse Suprachiasmatic Nucleus

2003 ◽  
Vol 90 (3) ◽  
pp. 1589-1597 ◽  
Author(s):  
Jason Itri ◽  
Christopher S. Colwell
Keyword(s):  
Synaptic Transmission ◽  
Receptor Antagonist ◽  
Kinetic Parameters ◽  
Mean Amplitude ◽  
Dependent Manner ◽  
Patch Clamp Recording ◽  
Inhibitory Synaptic Transmission ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
The Mean

Circadian rhythmicity in mammals is generated by a pair of nuclei in the anterior hypothalamus known as the suprachiasmatic nuclei (SCN), whose neurons express a variety of neuropeptides that are thought to play an important role in the circadian timing system. To evaluate the influence of VIP on inhibitory synaptic transmission between SCN neurons, we used whole cell patch-clamp recording in an acute brain slice preparation of mouse SCN. Baseline spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) varied significantly between regions and across phases, with a greater frequency of IPSCs observed in the dorsomedial region during the early night. Bath-applied VIP caused a significant increase in the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) in a reversible and dose-dependent manner with no effect on the mean amplitude or kinetic parameters. The effect of VIP was widespread throughout the SCN and observed in both ventrolateral (VL) and dorsomedial (DM) regions. In the presence of tetrodotoxin, VIP increased the frequency of miniature IPSCs without affecting the mean magnitude or kinetic parameters. The magnitude of the enhancement by VIP was significantly larger during the day than during the night. Pretreatment with the VIP-PACAP receptor antagonist [Ac-Tyr1, D-Phe2]-GHRF 1-29 or the selective VPAC2 receptor antagonist PG 99-465 completely blocked the VIP-induced enhancement. The effect of VIP appears to be mediated by a cAMP/PKA-dependent mechanism as forskolin mimics, while the PKA antagonist H-89 blocks the observed enhancement of GABA currents. Our data suggest that VIP activates presynaptic VPAC2 receptors to regulate inhibitory synaptic transmission within the SCN and that this effect varies from day to night.

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.

Persistent hyperexcitability in isolated hippocampal CA1 of kainate-lesioned rats

1992 ◽  
Vol 68 (6) ◽  
pp. 2120-2127 ◽  
Author(s):  
C. L. Meier ◽  
A. Obenaus ◽  
F. E. Dudek
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Sclerosis ◽  
Mean Amplitude ◽  
Cell Loss ◽  
Stratum Radiatum ◽  
Excitatory Postsynaptic Potential ◽  
Population Spikes ◽  
Acute Seizures ◽  
Postsynaptic Potential ◽  
Area Ca1

1. Subcutaneous kainate injection in rats evoked acute seizures and led to cell loss in the hilus and areas CA1 and CA3, which resembled the pattern of hippocampal sclerosis often associated with temporal lobe epilepsy in humans. 2. Simultaneous intra- and extracellular recordings were performed in the stratum pyramidale of area CA1 while stimulating in the stratum radiatum close to the recording electrodes. Responses from control slices consisted of a brief excitatory postsynaptic potential (EPSP) with only one action potential, corresponding to a single extracellular population spike, followed by a clear biphasic inhibitory postsynaptic potential (IPSP). In slices from kainate-treated animals, however, stimulation evoked a prolonged EPSP, which often triggered multiple action potentials corresponding to multiple extracellular population spikes. 3. In slices from kainate-treated animals, the mean amplitude but not the duration of the stimulation-evoked IPSP was reduced. The extent of the kainate-induced loss of inhibition in area CA1 was highly variable. 4. Low concentrations of bicuculline in control slices led to a moderate hyperexcitability, which consisted of multiple population spikes and mirrored the responses observed in slices from kainate-treated animals in normal ACSF. Prolonged application of 10-30 microM bicuculline for > or = 30 min led to a much higher level of hyperexcitability, which was similar in slices from controls and kainate-treated rats. These findings are consistent with the hypothesis that the hyperexcitability of CA1 pyramidal neurons following kainate treatment is mainly due to decreased GABAA-receptor-mediated inhibition and that the loss of inhibition is only partial.(ABSTRACT TRUNCATED AT 250 WORDS)

Giant, TTX-insensitive, inhibitory postsynaptic currents in cultured rat spinal cord and medullary neurons

1996 ◽  
Vol 76 (5) ◽  
pp. 3341-3350 ◽  
Author(s):  
C. A. Lewis ◽  
D. S. Faber
Keyword(s):  
Spinal Cord ◽  
Amplitude Ratio ◽  
Mean Amplitude ◽  
Prolonged Release ◽  
Whole Cell ◽  
Mean Values ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Order Of Magnitude ◽  
Medullary Neurons

1. In whole cell patch-clamp studies on cultured rat embryonic spinal cord and medullary neurons bathed in tetrodotoxin, DL-2-amino-5-phosphonovaleric acid, and 6-cyano-7-nitroquinoxaline-2,3-dione, large and long-lasting spontaneous inhibitory postsynaptic currents were occasionally recorded. The amplitudes of these events were 1 order of magnitude larger than those of spontaneous miniature inhibitory postsynaptic currents. Because these large currents had reduced amplitudes in calcium-free saline and in solutions containing glycinergic or GABAergic antagonists, we conclude that they were probably produced by large and prolonged release of glycine and/or 4-amino-n-butyric acid (GABA), which subsequently bind to their postsynaptic receptors. 2. The frequency of spontaneous miniature postsynaptic currents increased dramatically during the long, slow decay phase of these large postsynaptic currents. Considering the requirement for extracellular calcium for the occurrence of these large responses, we hypothesize that this increased frequency reflected an increased intracellular calcium concentration in the presynaptic terminal. 3. Similar evidence for large inhibitory postsynaptic currents and prolonged transmitter release was observed in cell-attached patches, which also exhibited the smaller, spontaneous miniature inhibitory postsynaptic currents, suggesting that these large events are properties of single synaptic terminals. 4. A comparison of the properties of these large inhibitory postsynaptic currents recorded in whole cell mode or cell-attached patches showed no statistically significant differences. The overall mean values, then, are 13.9 +/- 1.6 (SE) ms and 4.5 +/- 0.5 s for the 10-90% rise time and duration, respectively. Furthermore, these large events had amplitudes that were 11-fold larger than the mean amplitude of the miniatures (i.e., mean amplitude ratio of 10.8 +/- 0.5). 5. Periodic large increases in the frequency of spontaneous miniature inhibitory postsynaptic currents occurred in both cell-attached patches and in the whole cell mode, and these increases were only sometimes associated with the large inhibitory postsynaptic currents. The rhythmicity in both recording configurations had similar temporal characteristics, with average interburst intervals of 5 and 12–14 s. Presumably these bursts of spontaneous miniature postsynaptic currents reflected periodic oscillations in the Ca2+ concentration in presynaptic terminals. 6. Both the probability and the frequency of occurrence of large inhibitory postsynaptic currents doubled during the 7-day period of time in culture when experiments were performed, suggesting that these large currents may play a role during development.

scholarly journals Homeostatic Plasticity Hypothesis and Mechanisms of Neocortical Epilepsies

2005 ◽  
Vol 5 (4) ◽  
pp. 133-135 ◽  
Author(s):  
Jaideep Kapur ◽  
Stacey Trotter
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Activity ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Homeostatic Plasticity ◽  
Excitatory Synapses ◽  
Excitatory Postsynaptic Currents ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Homeostatic Synaptic Plasticity

Homeostatic Synaptic Plasticity Can Explain Posttraumatic Epileptogenesis in Chronically Isolated Neocortex Houweling AR, Bazhenov M, Timofeev I, Steriade M, Sejnowski TJ Cereb Cortex 2004 [Epub ahead of print] Permanently isolated neocortex develops chronic hyperexcitability and focal epileptogenesis in a period of days to weeks. The mechanisms operating in this model of posttraumatic epileptogenesis are not well understood. We hypothesized that the spontaneous burst discharges recorded in permanently isolated neocortex result from homeostatic plasticity (a mechanism generally assumed to stabilize neuronal activity) induced by low neuronal activity after deafferentation. To test this hypothesis, we constructed computer models of neocortex incorporating a biologically based homeostatic plasticity rule that operates to maintain firing rates. After deafferentation, homeostatic upregulation of excitatory synapses on pyramidal cells, either with or without concurrent downregulation of inhibitory synapses or upregulation of intrinsic excitability, initiated slowly repeating burst discharges that closely resembled the epileptiform burst discharges recorded in permanently isolated neocortex. These burst discharges lasted a few hundred milliseconds, propagated at 1 to 3 cm/s and consisted of large (10–15 mV) intracellular depolarizations topped by a small number of action potentials. Our results support a role for homeostatic synaptic plasticity as a novel mechanism of posttraumatic epileptogenesis. Excitatory and Inhibitory Postsynaptic Currents in a Rat Model of Epileptogenic Microgyria Jacobs KM, Prince DA J Neurophysiol 2005;93:687–696 Developmental cortical malformations are common in patients with intractable epilepsy; however, mechanisms contributing to this epileptogenesis are currently poorly understood. We previously characterized hyperexcitability in a rat model that mimics the histopathology of human four-layered microgyria. Here we examined inhibitory and excitatory postsynaptic currents in this model to identify functional alterations that might contribute to epileptogenesis associated with microgyria. We recorded isolated whole-cell excitatory postsynaptic currents and GABAA receptor–mediated inhibitory currents from layer V pyramidal neurons in the region previously shown to be epileptogenic (paramicrogyral area) and in homotopic control cortex. Epileptiform-like activity could be evoked in 60% of paramicrogyral (PMG) cells by local stimulation. The peak conductance of both spontaneous and evoked inhibitory postsynaptic currents was significantly larger in all PMG cells compared with controls. This difference in amplitude was not present after blockade of ionotropic glutamatergic currents or for miniature (m) inhibitory postsynaptic currents, suggesting that it was due to the excitatory afferent activity driving inhibitory neurons. This conclusion was supported by the finding that glutamatereceptor antagonist application resulted in a significantly greater reduction in spontaneous inhibitory postsynaptic current frequency in one PMG cell group (PMGE) compared with control cells. The frequency of both spontaneous and miniature excitatory postsynaptic currents was significantly greater in all PMG cells, suggesting that pyramidal neurons adjacent to a microgyrus receive more excitatory input than do those in control cortex. These findings suggest that there is an increase in numbers of functional excitatory synapses on both interneurons and pyramidal cells in the PMG cortex, perhaps due to hyperinnervation by cortical afferents originally destined for the microgyrus proper.

scholarly journals Streptozotocin Inhibits Electrophysiological Determinants of Excitatory and Inhibitory Synaptic Transmission in CA1 Pyramidal Neurons of Rat Hippocampal Slices: Reduction of These Effects by Edaravone

2016 ◽  
Vol 40 (6) ◽  
pp. 1274-1288 ◽  
Author(s):  
Ting Ju ◽  
Yuru Li ◽  
Xiaoran Wang ◽  
Lifeng Xiao ◽  
Li Jiang ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Paired Pulse ◽  
Ca1 Pyramidal Neurons ◽  
Postsynaptic Currents ◽  
Pulse Ratio ◽  
Synaptic Mechanisms

Background: Streptozotocin (STZ) has served as an agent to generate an Alzheimer's disease (AD) model in rats, while edaravone (EDA), a novel free radical scavenger, has recently emerged as an effective treatment for use in vivo and vitro AD models. However, to date, these beneficial effects of EDA have only been clearly demonstrated within STZ-induced animal models of AD and in cell models of AD. A better understanding of the mechanisms of EDA may provide the opportunity for their clinical application in the treatment of AD. Therefore, the purpose of this study was to investigate the underlying mechanisms of STZ and EDA as assessed upon electrophysiological alterations in CA1 pyramidal neurons of rat hippocampal slices. Methods: Through measures of evoked excitatory postsynaptic currents (eEPSCs), AMPAR-mediated eEPSCs (eEPSCsAMPA), evoked inhibitory postsynaptic currents (eIPSCs), evoked excitatory postsynaptic current paired pulse ratio (eEPSC PPR) and evoked inhibitory postsynaptic current paired pulse ratio (eIPSC PPR), it was possible to investigate mechanisms as related to the neurotoxicity of STZ and reductions in these effects by EDA. Results: Our results showed that STZ (1000 µM) significantly inhibited peak amplitudes of eEPSCs, eEPSCsAMPA and eIPSCs, while EDA (1000 µM) attenuated these STZ-induced changes at holding potentials ranging from -60mV to +40 mV for EPSCs and -60mV to +20 mV for IPSCs. Our work also indicated that mean eEPSC PPR were substantially altered by STZ, effects which were partially restored by EDA. In contrast, no significant effects upon eIPSC PPR were obtained in response to STZ and EDA. Conclusion: Our data suggest that STZ inhibits glutamatergic transmission involving pre-synaptic mechanisms and AMPAR, and that STZ inhibits GABAergic transmission by post-synaptic mechanisms within CA1 pyramidal neurons. These effects are attenuated by EDA.

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