scholarly journals Miniature Inhibitory Postsynaptic Currents in CA1 Pyramidal Neurons After Kindling Epileptogenesis

1999 ◽  
Vol 82 (3) ◽  
pp. 1352-1362 ◽  
Author(s):  
Corette J. Wierenga ◽  
Wytse J. Wadman
Keyword(s):  
Pyramidal Neurons ◽  
Single Channel ◽  
Noise Analysis ◽  
Specific Class ◽  
Inhibitory Postsynaptic Currents ◽  
Ca1 Pyramidal Neurons ◽  
Postsynaptic Currents ◽  
Generalized Seizures ◽  
Significant Difference ◽  
The Difference

Miniature inhibitory postsynaptic currents (mIPSCs) were measured in CA1 pyramidal neurons from long-term kindled rats (>6 weeks after they reached the stage of generalized seizures) and compared with controls. A large reduction in the number of mIPSCs was observed in a special group of large mIPSCs (amplitude >75 pA). The frequency of mIPSCs in this group was reduced from 0.042 Hz in controls to 0.027 Hz in the kindled animals. The reduction in this group resulted in a highly significant difference in the amplitude distributions. A distinction was made between fast mIPSCs (rise time <2.8 ms) and slow mIPSCs. Fast mIPSCs, which could originate from synapses onto the soma and proximal dendrites, had significantly larger amplitudes than slow mIPSCs, which could originate from more distal synapses (35.4 ± 1.1 vs. 26.2 ± 0.4 pA in the kindled group; means ± SE). The difference in the value of the mean of all amplitudes and frequency of fast and slow mIPSCs did not reach significance when the kindled group was compared with controls. The mIPSC kinetics were not different after kindling, from which we conclude that the receptor properties had not changed. Nonstationary noise analysis of the largest mIPSCs suggested that the single-channel conductance and the number of postsynaptic receptors was similar in the kindled and control groups. Our results suggest a 40–50% reduction in a small fraction of (peri-) somatic synapses with large or complex postsynaptic structure after kindling. This functionally relevant reduction may be related to previously observed loss of a specific class of interneurons. Our findings are consistent with a reduction in inhibitory drive in the CA1 area. Such a reduction could underlie the enhanced seizure susceptibility after kindling epileptogenesis.

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.

Impaired Cl− Extrusion in Layer V Pyramidal Neurons of Chronically Injured Epileptogenic Neocortex

2005 ◽  
Vol 93 (4) ◽  
pp. 2117-2126 ◽  
Author(s):  
Xiaoming Jin ◽  
John R. Huguenard ◽  
David A. Prince
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Gabaergic Inhibition ◽  
Adult Rats ◽  
Positive Shift ◽  
Mature Brain ◽  
Significant Difference ◽  
The Difference ◽  
Layer V ◽  
Patch Technique

In the mature brain, the K+/Cl− cotransporter KCC2 is important in maintaining low [Cl−]i, resulting in hyperpolarizing GABA responses. Decreases in KCC2 after neuronal injuries result in increases in [Cl−]i and enhanced neuronal excitability due to depolarizing GABA responses. We used the gramicidin perforated-patch technique to measure ECl (∼ EGABA) in layer V pyramidal neurons in slices of partially isolated sensorimotor cortex of adult rats to explore the potential functional consequence of KCC2 downregulation in chronically injured cortex. EGABA was measured by recording currents evoked with brief GABA puffs at various membrane potentials. There was no significant difference in ECl between neurons in control and undercut animals (–71.2 ± 2.6 and –71.8 ± 2.8 mV, respectively). However, when loaded with Cl− by applying muscimol puffs at 0.2 Hz for 60 s, neurons in the undercut cortex had a significantly shorter time constant for the positive shift in ECl during the Cl− loading phase (4.3 ± 0.5 s for control and 2.2 ± 0.4 s for undercut, P < 0.01). The positive shift in ECl 3 s after the beginning of Cl− loading was also significantly larger in the undercut group than in the control, indicating that neurons in undercut cortex were less effective in maintaining low [Cl−]i during repetitive activation of GABAA receptors. Application of furosemide eliminated the difference between the control and undercut groups for both of these measures of [Cl−]i regulation. The results suggest an impairment in Cl− extrusion resulting from decreased KCC2 expression that may reduce the strength of GABAergic inhibition and contribute to epileptogenesis.

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.

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