Hippocampal seizures and failure of inhibition

1979 ◽  
Vol 57 (12) ◽  
pp. 1462-1466 ◽  
Author(s):  
Y. Ben-Ari ◽  
K. Krnjević ◽  
W. Reinhardt
Keyword(s):  
Pyramidal Neurons ◽  
Repetitive Stimulation ◽  
Perforant Path ◽  
Tetanic Stimulation ◽  
Postsynaptic Potential ◽  
Entorhinal Area ◽  
Ca3 Pyramidal Neurons ◽  
Input Conductance ◽  
Conductance Increase ◽  
Hippocampal Seizures

The powerful inhibition of CA3 pyramidal neurons evoked in rats (under urethane) by stimulating the fimbria or the perforant path from the entorhinal area is associated with a large increase in input conductance. Microiontophoretic applications of GABA produce a very similar large conductance increase, which is characterized by rapid fading, and causes a marked depression of the inhibitory postsynaptic potential (IPSP) conductance change. During repetitive stimulation at frequencies as low as 3–5/s, the IPSP conductance change can be much reduced, and it vanishes when electrical seizures begin. Since the effect of GABA is also reduced or abolished, a loss of efficacy of GABA (caused by desensitization or some other process) may be responsible for the failure of inhibition observed during tetanic stimulation, as well as for the subsequent seizures.

Selective Shunting of the NMDA EPSP Component by the Slow Afterhyperpolarization in Rat CA1 Pyramidal Neurons

2007 ◽  
Vol 97 (5) ◽  
pp. 3242-3255 ◽  
Author(s):  
David Fernández de Sevilla ◽  
Marco Fuenzalida ◽  
Ana B. Porto Pazos ◽  
Washington Buño
Keyword(s):  
Pyramidal Neurons ◽  
Spatial Summation ◽  
Decisive Role ◽  
Perforant Path ◽  
Ca1 Pyramidal Neurons ◽  
Basal Dendrites ◽  
Hippocampal Ca1 ◽  
Dendritic Location ◽  
Conductance Increase

Pyramidal neuron dendrites express voltage-gated conductances that control synaptic integration and plasticity, but the contribution of the Ca2+-activated K+-mediated currents to dendritic function is not well understood. Using dendritic and somatic recordings in rat hippocampal CA1 pyramidal neurons in vitro, we analyzed the changes induced by the slow Ca2+-activated K+-mediated afterhyperpolarization (sAHP) generated by bursts of action potentials on excitatory postsynaptic potentials (EPSPs) evoked at the apical dendrites by perforant path-Schaffer collateral stimulation. Both the amplitude and decay time constants of EPSPs (τEPSP) were reduced by the sAHP in somatic recordings. In contrast, the dendritic EPSP amplitude remained unchanged, whereas τEPSP was reduced. Temporal summation was reduced and spatial summation linearized by the sAHP. The amplitude of the isolated N-methyl-d-aspartate component of EPSPs (EPSPNMDA) was reduced, whereas τNMDA was unaffected by the sAHP. In contrast, the sAHP did not modify the amplitude of the isolated EPSPAMPA but reduced τAMPA both in dendritic and somatic recordings. These changes are attributable to a conductance increase that acted mainly via a selective “shunt” of EPSPNMDA because they were absent under voltage clamp, not present with imposed hyperpolarization simulating the sAHP, missing when the sAHP was inhibited with isoproterenol, and reduced under block of EPSPNMDA. EPSPs generated at the basal dendrites were similarly modified by the sAHP, suggesting both a somatic and apical dendritic location of the sAHP channels. Therefore the sAHP may play a decisive role in the dendrites by regulating synaptic efficacy and temporal and spatial summation.

scholarly journals An optogenetic method for investigating presynaptic molecular regulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuni Kay ◽  
Bruce E. Herring
Keyword(s):  
Pyramidal Neurons ◽  
Molecular Regulation ◽  
Glutamatergic Synapses ◽  
Experimental Conditions ◽  
Regulatory Pathways ◽  
Genetic Manipulations ◽  
Postsynaptic Protein ◽  
Presynaptic Function ◽  
Synaptotagmin 1 ◽  
Ca3 Pyramidal Neurons

AbstractWhile efficient methods are well established for studying postsynaptic protein regulation of glutamatergic synapses in the mammalian central nervous system, similarly efficient methods are lacking for studying proteins regulating presynaptic function. In the present study, we introduce an optical/electrophysiological method for investigating presynaptic molecular regulation. Here, using an optogenetic approach, we selectively stimulate genetically modified presynaptic CA3 pyramidal neurons in the hippocampus and measure optically-induced excitatory postsynaptic currents produced in unmodified postsynaptic CA1 pyramidal neurons. While such use of optogenetics is not novel, previous implementation methods do not allow basic quantification of the changes in synaptic strength produced by genetic manipulations. We find that incorporating simultaneous recordings of fiber volley amplitude provides a control for optical stimulation intensity and, as a result, creates a metric of synaptic efficacy that can be compared across experimental conditions. In the present study, we utilize our new method to demonstrate that inhibition of synaptotagmin 1 expression in CA3 pyramidal neurons leads to a significant reduction in Schaffer collateral synapse function, an effect that is masked with conventional electrical stimulation. Our hope is that this method will expedite our understanding of molecular regulatory pathways that govern presynaptic function.

scholarly journals Liraglutide modulates GABAergic signaling in rat hippocampal CA3 pyramidal neurons predominantly by presynaptic mechanism

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Omar Babateen ◽  
Sergiy V. Korol ◽  
Zhe Jin ◽  
Amol K. Bhandage ◽  
Aikeremu Ahemaiti ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Ca3 ◽  
Ca3 Pyramidal Neurons

Characterization of synaptically mediated fast and slow inhibitory processes in piriform cortex in an in vitro slice preparation

1988 ◽  
Vol 59 (5) ◽  
pp. 1352-1376 ◽  
Author(s):  
G. F. Tseng ◽  
L. B. Haberly
Keyword(s):  
Membrane Potential ◽  
Piriform Cortex ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Membrane Depolarization ◽  
Resting Membrane Potential ◽  
Excitatory Postsynaptic Potential ◽  
Pentobarbital Sodium ◽  
Postsynaptic Potential ◽  
Conductance Increase

1. Intracellular recordings were obtained from anatomically verified layer II pyramidal cells in slices from rat piriform cortex cut perpendicular to the surface. 2. Responses to afferent and association fiber stimulation at resting membrane potential consisted of a depolarizing potential followed by a late hyperpolarizing potential (LHP). Membrane polarization by current injection revealed two components in the depolarizing potential: an initial excitatory postsynaptic potential (EPSP) followed at brief latency by an inhibitory postsynaptic potential (IPSP) that inverted with membrane depolarization and truncated the duration of the EPSP. 3. The early IPSP displayed the following characteristics suggesting mediation by gamma-aminobutyric acid (GABA) receptors linked to Cl- channels: associated conductance increase, sensitivity to increases in internal Cl- concentration, blockage by picrotoxin and bicuculline, and potentiation by pentobarbital sodium. The reversal potential was in the depolarizing direction with respect to resting membrane potential so that the inhibitory effect was exclusively via current shunting. 4. The LHP had an associated conductance increase and a reversal potential of -90 mV in normal bathing medium that shifted according to Nernst predictions for a K+ potential with changes in external K+ over the range 4.5-8 mM indicating mediation by the opening of K+ channels and ruling out an electrogenic pump origin. 5. Lack of effect of bath-applied 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) or internally applied ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) on the LHP and failure of high amplitude, direct membrane depolarization to evoke a comparable potential, argue against endogenous mediation of the LHP by a Ca2+ activated K+ conductance [gK(Ca)]. However, an apparent endogenously mediated gK(Ca) with a duration much greater than the LHP was observed in a low percent of layer II pyramidal cells. Lack of effect of 8-Br-cAMP also indicates a lack of dependence of the LHP on cAMP. 6. Other characteristics of the LHP that were demonstrated include: a lack of blockage by GABAA receptor antagonists, a probable voltage sensitivity (decrease in amplitude in the depolarizing direction), and an apparent brief onset latency (less than 10 ms) when the early IPSP was blocked by picrotoxin. The LHP was unaffected by pentobarbital sodium when the early IPSP was blocked by picrotoxin. 7. Both the LHP and early IPSP were blocked by low Ca2+/high Mg2+, consistent with disynaptic mediation.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of voltage-gated and synaptic conductances contributing to network excitability defects in the mutant mouse tottering

1994 ◽  
Vol 71 (1) ◽  
pp. 1-10 ◽  
Author(s):  
S. A. Helekar ◽  
J. L. Noebels
Keyword(s):  
Gabaa Receptor ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Channel Blockers ◽  
Gamma Aminobutyric Acid ◽  
Voltage Gated ◽  
Voltage Dependent ◽  
Prolonged Duration ◽  
Ca3 Pyramidal Neurons ◽  
The Difference

1. Intracellular current- and voltage-clamp recordings were carried out in CA3 pyramidal neurons from hippocampal slices of adult tg/tg mice and their coisogenic C57BL/6J (+/+) controls with the use of the single-electrode switch-clamp technique. The principal aim of this study was to investigate the mechanisms responsible for the tg gene-linked prolongation (mean 60%) of a giant synaptic response, the potassium-induced paroxysmal depolarizing shift (PDS) at depolarized membrane potentials (Vm -47 to -54 mV) during synchronous network bursting induced by 10 mM potassium ([K+]o). 2. To examine the role of intrinsic voltage-dependent conductances underlying the mutant PDS prolongation, neurons were voltage clamped by the use of microelectrodes filled with 100 mM QX-314 or QX-222 chloride (voltage-gated sodium channel blockers) and 2 M cesium sulphate (potassium channel blocker). The whole-cell currents active during the PDS showed a significantly prolonged duration (mean 34%) at depolarized Vms in tg/tg compared with +/+ cells, indicating that a defect in voltage-dependent conductances is unlikely to completely account for the mutant phenotype. 3. Bath application of 40 microM (DL)-2-aminophosphonovalerate (DL-APV) produced a 30% reduction in PDS duration in both genotypes but failed to significantly alter the tg gene-linked prolongation compared with the wild type. These data indicate that the mutant PDS abnormality does not result from a selective increase of the N-methyl-D-aspartate (NMDA) receptor-mediated excitatory synaptic component. 4. Blockade of gamma-aminobutyric acid-A (GABAA) transmission with picrotoxin (50 microM) or bicuculline (1–5 microM) completely eliminated the difference in PDS duration between the genotypes. Furthermore, although both GABAA receptor antagonists increased the mean PDS duration in +/+ neurons, they did not significantly alter it in tg/tg neurons. These findings are consistent with a reduction in GABAA receptor-mediated synaptic inhibition during bursting in the tg CA3 hippocampal network. 5. To test this hypothesis, bursting CA3 pyramidal neurons were loaded intracellularly with chloride by the use of KCl-filled microelectrodes to examine the effect of reversing the hyperpolarizing chloride-dependent GABAA receptor-mediated inhibitory postsynaptic component of the PDS. Chloride loading prolonged PDS duration in both genotypes, but the increase was greater in +/+ than in tg/tg neurons, indicating that a smaller GABAA inhibitory postsynaptic potential (IPSP) component was reversed in the mutant.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Computational Analysis of the Impact of Chronic Stress on Intrinsic and Synaptic Excitability in the Hippocampus

2010 ◽  
Vol 103 (6) ◽  
pp. 3070-3083 ◽  
Author(s):  
Rishikesh Narayanan ◽  
Sumantra Chattarji
Keyword(s):  
Chronic Stress ◽  
Pyramidal Neurons ◽  
Three Dimensional ◽  
Input Resistance ◽  
Synaptic Potentiation ◽  
Synaptic Inputs ◽  
Hippocampal Ca3 ◽  
Ca3 Pyramidal Neurons ◽  
Dendritic Atrophy ◽  
The Impact

Dendritic atrophy and impaired long-term synaptic potentiation (LTP) are hallmarks of chronic stress-induced plasticity in the hippocampus. It has been hypothesized that these disparate structural and physiological correlates of stress lead to hippocampal dysfunction by reducing postsynaptic dendritic surface, thereby adversely affecting the availability of synaptic inputs and suppressing LTP. Here we examine the validity of this framework using biophysical models of hippocampal CA3 pyramidal neurons. To statistically match with the experimentally observed region specificity of stress-induced atrophy, we use an algorithm to systematically prune three-dimensional reconstructions of CA3 pyramidal neurons. Using this algorithm, we build a biophysically realistic computational model to analyze the effects of stress on intrinsic and synaptic excitability. We find that stress-induced atrophy of CA3 dendrites leads to an increase in input resistance, which depends exponentially on the percentage of neuronal atrophy. This increase translates directly into higher spiking frequencies in response to both somatic current injections and synaptic inputs at various locations along the dendritic arbor. Remarkably, we also find that the dendritic regions that manifest atrophy-induced synaptic hyperexcitability are governed by the region specificity of the underlying dendritic atrophy. Coupled with experimentally observed modulation of N-methyl-d-aspartate receptor currents, such hyperexcitability could tilt the balance of plasticity mechanisms in favor of synaptic potentiation over depression. Thus paradoxically, our results suggest that stress may impair hippocampal learning and memory, not by directly inhibiting LTP, but because of stress-induced facilitation of intrinsic and synaptic excitability and the consequent imbalance in bidirectional synaptic plasticity.

scholarly journals Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer

2019 ◽  
Author(s):  
Nuno Apóstolo ◽  
Samuel N. Smukowski ◽  
Jeroen Vanderlinden ◽  
Giuseppe Condomitti ◽  
Vasily Rybakin ◽  
...  
Keyword(s):  
Cell Surface ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Surface Protein ◽  
Guidance Cue ◽  
Hippocampal Ca3 ◽  
Cell Surface Interactions ◽  
Ca3 Pyramidal Neurons ◽  
Ca3 Neurons ◽  
Multiple Ligand

SummarySynaptic diversity is a key feature of neural circuits. The structural and functional diversity of closely spaced inputs converging on the same neuron suggests that cell-surface interactions are essential in organizing input properties. Here, we analyzed the cell-surface protein (CSP) composition of hippocampal mossy fiber (MF) inputs on CA3 pyramidal neurons to identify regulators of MF-CA3 synapse properties. We uncover a rich cell-surface repertoire that includes adhesion proteins, guidance cue receptors, extracellular matrix (ECM) proteins, and uncharacterized CSPs. Interactome screening reveals multiple ligand-receptor modules and identifies ECM protein Tenascin-R (TenR) as a ligand of the uncharacterized neuronal receptor IgSF8. Presynaptic Igsf8 deletion impairs MF-CA3 synaptic architecture and robustly decreases the density of bouton filopodia that provide feedforward inhibition of CA3 neurons. Consequently, loss of IgSF8 increases CA3 neuron excitability. Our findings identify IgSF8 as a regulator of CA3 microcircuit development and suggest that combinations of CSP modules define input identity.

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