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2.
Sci Data ; 7(1): 78, 2020 03 04.
Article in English | MEDLINE | ID: mdl-32132545

ABSTRACT

A challenge for data sharing in systems neuroscience is the multitude of different data formats used. Neurodata Without Borders: Neurophysiology 2.0 (NWB:N) has emerged as a standardized data format for the storage of cellular-level data together with meta-data, stimulus information, and behavior. A key next step to facilitate NWB:N adoption is to provide easy to use processing pipelines to import/export data from/to NWB:N. Here, we present a NWB-formatted dataset of 1863 single neurons recorded from the medial temporal lobes of 59 human subjects undergoing intracranial monitoring while they performed a recognition memory task. We provide code to analyze and export/import stimuli, behavior, and electrophysiological recordings to/from NWB in both MATLAB and Python. The data files are NWB:N compliant, which affords interoperability between programming languages and operating systems. This combined data and code release is a case study for how to utilize NWB:N for human single-neuron recordings and enables easy re-use of this hard-to-obtain data for both teaching and research on the mechanisms of human memory.


Subject(s)
Information Dissemination , Information Storage and Retrieval/standards , Memory , Neurons/physiology , Electrophysiological Phenomena , Humans , Software , Temporal Lobe/cytology
3.
Cereb Cortex ; 25(3): 578-97, 2015 Mar.
Article in English | MEDLINE | ID: mdl-24046077

ABSTRACT

Electrophysiological oscillations are thought to create temporal windows of communication between brain regions. We show here that human cortical slices maintained in vitro can generate oscillations similar to those observed in vivo. We have characterized these oscillations using local field potential and whole-cell recordings obtained from neocortical slices acquired during epilepsy surgery. We confirmed that such neocortical slices maintain the necessary cellular and circuitry components, and in particular inhibitory mechanisms, to manifest oscillatory activity when exposed to glutamatergic and cholinergic agonists. The generation of oscillations was dependent on intact synaptic activity and muscarinic receptors. Such oscillations differed in electrographic and pharmacological properties from epileptiform activity. Two types of activity, theta oscillations and high gamma activity, uniquely characterized this model-activity not typically observed in animal cortical slices. We observed theta oscillations to be synchronous across cortical laminae suggesting a novel role of theta as a substrate for interlaminar communication. As well, we observed cross-frequency coupling (CFC) between theta phase and high gamma amplitude similar to that observed in vivo. The high gamma "bursts" generated by such CFC varied in their frequency content, suggesting that this variability may underlie the broadband nature of high gamma activity.


Subject(s)
Gamma Rhythm , Interneurons/physiology , Neocortex/physiology , Pyramidal Cells/physiology , Temporal Lobe/physiology , Theta Rhythm , Adult , Aged , Carbachol/pharmacology , Cholinergic Agonists/pharmacology , Excitatory Amino Acid Agonists/pharmacology , Female , Gamma Rhythm/drug effects , Humans , In Vitro Techniques , Interneurons/drug effects , Kainic Acid/pharmacology , Male , Membrane Potentials/drug effects , Middle Aged , Neocortex/drug effects , Pyramidal Cells/drug effects , Receptors, Muscarinic/physiology , Temporal Lobe/drug effects , Theta Rhythm/drug effects , Young Adult
4.
Epilepsy Res ; 97(3): 290-9, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22075227

ABSTRACT

One of the most terrifying aspects of epilepsy is the sudden and apparently unpredictable transition of the brain into the pathological state of an epileptic seizure. The pathophysiology of the transition to seizure still remains mysterious. Herein we review some of the key concepts and relevant literatures dealing with this enigmatic transitioning of brain states. At the "MACRO" level, electroencephalographic (EEG) recordings at time display preictal phenomena followed by pathological high-frequency oscillations at the seizure onset. Numerous seizure prediction algorithms predicated on identifying changes prior to seizure onset have met with little success, underscoring our lack of understanding of the dynamics of transition to seizure, amongst other inherent limitation. We then discuss the concept of synchronized hyperexcited oscillatory networks underlying seizure generation. We consider these networks as weakly coupled oscillators, a concept which forms the basis of some relevant mathematical modeling of seizure transitions. Next, the underlying "MICRO" processes involved in seizure generation are discussed. The depolarization of the GABA(A) chloride reversal potential is a major concept, facilitating epileptogenesis, particularly in immature brain. Also the balance of inhibitory and excitatory local neuronal networks plays an important role in the process of transitioning to seizure. Gap junctional communication, including that which occurs between glia, as well as ephaptic interactions are increasingly recognized as critical for seizure generation. In brief, this review examines the evidence regarding the characterization of the transition to seizure at both the "MACRO" and "MICRO" levels, trying to characterize this mysterious yet critical problem of the brain state transitioning into a seizure.


Subject(s)
Brain/pathology , Brain/physiopathology , Neurons/physiology , Seizures/pathology , Seizures/physiopathology , Electroencephalography , Humans , Models, Neurological , Nerve Net/physiopathology , Predictive Value of Tests , Signal Processing, Computer-Assisted , Synapses/pathology , gamma-Aminobutyric Acid/metabolism
5.
Arch Ital Biol ; 148(3): 289-97, 2010 Sep.
Article in English | MEDLINE | ID: mdl-21175015

ABSTRACT

Patients with mesial temporal lobe epilepsy (mTLE) show structural and functional abnormalities in hippocampus and surrounding mesial temporal structures. Brain signal complexity appears to be a marker of functional integrity or capacity. We examined complexity in 8 patients with intracranial hippocampal electrodes during performance of memory tasks (scene encoding and recognition) known to be sensitive to mesial temporal integrity. Our patients were shown to have right mesial temporal seizure onsets, permitting us to evaluate both epileptogenic (right) and healthy (left) hippocampi. Using multiscale entropy (MSE) as a measure of complexity, we found that iEEG from the epileptogenic hippocampus showed less complexity than iEEG from the healthy hippocampus. This difference was reliable for encoding but not for recognition. Our results indicate that both functional integrity and cognitive demands influence hippocampal signal complexity.


Subject(s)
Cognition/physiology , Epilepsy, Temporal Lobe/pathology , Functional Laterality/physiology , Hippocampus/physiopathology , Memory/physiology , Adult , Electroencephalography/methods , Entropy , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Temporal Lobe/physiopathology
7.
J Neurosurg ; 90(4): 673-9, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10193612

ABSTRACT

OBJECT: The authors sought to establish prospectively whether there is a simple relationship between radiological features of brain arteriovenous malformation (AVM) hemodynamics and a patient's clinical presentation. METHODS: Thirty-one consecutive patients with AVMs underwent cerebral angiography at 3.8 frames/second during each standardized injection of contrast material. Contrast dilution curves were derived from the image sequences by using regions of interest (ROIs) traced on arteries feeding and veins draining the AVM nidus. Angiographic parameters were then analyzed in a blinded fashion. These parameters included the times required to reach the peak contrast density, the contrast decay time, and fractions thereof, in the ROI for each vessel. The authors determined whether these parameters, the arteriovenous transit time, and/or AVM size were related to patients' presentation with hemorrhage (11 patients), seizure (11 patients), or other clinical symptoms (nine patients). Statistically significant results were found only in analyses of arterial phase times to reach peak contrast density. Analyses of venous parameters, AVM size, and nidus transit time showed trends but no statistical significance. Arterial filling with contrast material was significantly slower in patients presenting with hemorrhage (mean 50%, 80%, and 100% of time to peak +/- standard error [SE] = 1.19+/-0.13, 1.97+/-0.18, and 3.04+/-0.34 seconds, respectively) compared with patients presenting with seizures (mean 50%, 80%, and 100% of time to peak +/- SE = 0.80+/-0.12, 1.32+/-0.18, and 1.95+/-0.29 seconds, respectively) according to analysis of variance (p<0.05) and post-hoc t-tests (p<0.05) for each parameter. Patients who presented with other symptoms had intermediate arterial filling times. CONCLUSIONS: These simple hemodynamic parameters, which can be obtained without added risk to the patient, may help identify a subset of individuals in whom AVMs pose a higher risk of future hemorrhage and who may therefore warrant more expeditious treatment.


Subject(s)
Cerebral Angiography , Hemodynamics/physiology , Intracranial Arteriovenous Malformations/diagnostic imaging , Adult , Aged , Analysis of Variance , Cerebral Arteries/diagnostic imaging , Cerebral Arteries/physiopathology , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/physiopathology , Cerebral Veins/diagnostic imaging , Cerebral Veins/physiopathology , Cerebrovascular Circulation/physiology , Contrast Media/administration & dosage , Female , Humans , Image Processing, Computer-Assisted , Indicator Dilution Techniques , Intracranial Arteriovenous Malformations/physiopathology , Male , Middle Aged , Prospective Studies , Risk Factors , Seizures/diagnostic imaging , Seizures/physiopathology , Single-Blind Method , Time Factors
8.
J Physiol ; 499 ( Pt 1): 121-34, 1997 Feb 15.
Article in English | MEDLINE | ID: mdl-9061644

ABSTRACT

1. We have studied macroscopic current fluctuations associated with the after-hyperpolarization current (IAHP) that follows a 200 ms voltage-clamp step to 0 mV in dentate granule (DG) neurones of the rat hippocampus. This maximally effective stimulus produced a peak IAHP of 205 +/- 20 pA. Background noise was minimized by using the whole-cell single-electrode voltage-clamp configuration. 2. Conventional current-variance analysis was performed on IAHP to obtain estimates of the unitary AHP channel current (i) and the maximal attainable AHP current (Imax). A second approach, utilizing changes in the power spectrum of IAHP 'noise' during the decay of IAHP, was employed to yield an independent estimate of Imax as well as an estimate of the mean open-state duration of AHP channels. 3. Changes in the power spectrum during IAHP decay revealed that the mean channel open time is fixed at 6.9 +/- 0.5 ms and that the decay is due to changes in channel closed-state duration. The same analysis gave a value for Imax of 320 +/- 20 pA (n = 7). 4. Current-variance analysis suggests that channels responsible for generation of IAHP have a unitary current of 0.29 +/- 0.08 pA at -45 mV in 5 mM extracellular potassium and an Imax of 400 +/- 180 (n = 7). Thus, both methods indicate that about 1200 channels are available to generate IAHP in DG neurones and that about 60% are open at the peak of a maximal IAHP. 5. Computer simulations of IAHP currents in a model neurone show that dendritic current sources will result in an underestimation of i while Imax is underestimated to a lesser extent. Estimates of Imax obtained from power-spectrum analysis are more accurate and less affected by neuronal electrotonic structure than estimates of Imax based on current-variance analysis.


Subject(s)
Action Potentials/physiology , Hippocampus/physiology , Neurons/physiology , Animals , Male , Patch-Clamp Techniques , Rats , Rats, Wistar
9.
J Neurophysiol ; 78(6): 3107-16, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9405530

ABSTRACT

Direct electrical coupling between neurons can be the result of both electrotonic current transfer through gap junctions and extracellular fields. Intracellular recordings from CA1 pyramidal neurons of rat hippocampal slices showed two different types of small-amplitude coupling potentials: short-duration (5 ms) biphasic spikelets, which resembled differentiated action potentials and long-duration (>20 ms) monophasic potentials. A three-dimensional morphological model of a pyramidal cell was employed to determine the extracellular field produced by a neuron and its effect on a nearby neuron resulting from both gap junctional and electric field coupling. Computations were performed with a novel formulation of the boundary element method that employs triangular elements to discretize the soma and cylindrical elements to discretize the dendrites. An analytic formula was derived to aid in computations involving cylindrical elements. Simulation results were compared with biological recordings of intracellular potentials and spikelets. Field effects produced waveforms resembling spikelets although of smaller magnitude than those recorded in vitro. Gap junctional electrotonic connections produced waveforms resembling small-amplitude excitatory postsynaptic potentials. Intracellular electrode measurements were found inadequate for ascertaining membrane events because of externally applied electric fields. The transmembrane voltage induced by the electric field was highly spatially dependent in polarity and wave shape, as well as being an order of magnitude larger than activity measured at the electrode. Membrane voltages because of electrotonic current injection across gap junctions were essentially constant over the cell and were accurately depicted by the electrode. The effects of several parameters were investigated: 1) decreasing the ratio of intra to extracellular conductivity reduced the field effects; 2) the tree structure had a major impact on the intracellular potential; 3) placing the gap junction in the dendrites introduced a time delay in the gap junctional mediated electrotonic potential, as well as deceasing the potential recorded by the somatic electrode; and 4) field effects decayed to one-half of their maximum strength at a cell separation of approximately 20 micron. Results indicate that the in vitro measured spikelets are unlikely to be mediated by gap junctions and that a spikelet produced by the electric field of a single source cell has the same waveshape as the measured spikelet but with a much smaller amplitude. It is hypothesized that spikelets are a manifestation of the simultaneous electric field effects from several local cells whose action potential firing is synchronized.


Subject(s)
Computer Simulation , Models, Neurological , Pyramidal Cells/physiology , Action Potentials/physiology , Animals , Dendrites/physiology , Electric Conductivity , Gap Junctions/physiology , In Vitro Techniques , Membrane Potentials/physiology , Rats , Rats, Wistar
10.
J Neurophysiol ; 76(5): 3442-50, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8930284

ABSTRACT

1. The passive electrical properties of whole cell patched dentate granule cells were studied with the use of zero-mean Gaussian white noise current stimuli. Transmembrane voltage responses were used to compute the first-order Wiener kernels describing the current-voltage relationship at the soma for six cells. Frequency domain optimization techniques using a gradient method for function minimization were then employed to identify the optimal electrical parameter values. Low-power white noise stimuli are presented as a favorable alternative to the use of short-pulse current inputs for investigating neuronal passive electrical properties. 2. The optimization results demonstrated that the lumped resistive and capacitive properties of the recording electrode must be included in the analytic input impedance expression to optimally fit the measured cellular responses. The addition of the electrode resistance (Re) and capacitance (Ce) to the original parameters (somatic conductance, somatic capacitance, axial resistance, dendritic conductance, and dendritic capacitance) results in a seven-parameter model. The mean Ce value from the six cells was 5.4 +/- 0.3 (SE) pF, whereas Re following formation of the patch was found to be 20 +/- 2 M omega. 3. The six dentate granule cells were found to have an input resistance of 600 +/- 20 M omega and a dendritic to somatic conductance ratio of 6.3 +/- 1.1. The electronic length of the equivalent dendritic cylinder was found to be 0.42 +/- 0.03. The membrane time constant in the soma was found to be 13 +/- 3 ms, whereas the membrane time constant of the dendrites was 58 +/- 5 ms. Incorporation of morphological estimations led to the following distributed electrical parameters: somatic membrane resistance = 25 +/- 4 k omega cm2, somatic membrane capacitance = 0.48 +/- 0.05 microF/cm2, Ri (input resistance) = 72 +/- 5 omega cm, dendritic membrane resistance = 59 +/- 4 k omega cm2, and dendritic membrane capacitance = 0.97 +/- 0.06 microF/cm2. On the basis of capacitive measurements, the ratio of dendritic surface area to somatic surface area was found to be 34 +/- 2. 4. For comparative purposes, hyperpolarizing short pulses were also injected into each cell. The short-pulse input impedance measurements were found to underestimate the input resistance of the cell and to overestimate both the somatic conductance and the membrane time constants relative to the white noise input impedance measurements.


Subject(s)
Brain/physiology , Dendrites/physiology , Membrane Potentials/physiology , Neurons/physiology , Animals , Models, Neurological , Noise , Patch-Clamp Techniques , Rats , Rats, Wistar
11.
J Neurophysiol ; 76(4): 2691-700, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8899638

ABSTRACT

1. Whole cell recordings from dentate granule neurons in the hippocampal slice preparation reveal that (1 S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), a selective agonist at metabotropic glutamate receptors (mGluRs), inhibits a calcium-activated potassium current (IAHP) responsible for the postspike after-hyperpolarization. Inclusion of 1 mM of the Ca2+ chelator ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid in the patch pipette reduced the inhibitory action of ACPD on IAHP while having no effect on a similar action of serotonin (5-HT). Thus the known action of ACPD of mobilizing intracellular Ca2+ may be involved in this inhibitor action of ACPD. 2. Inhibition of IAHP is not secondary to effects on Ca2+ currents, because 10 microM ACPD, which inhibits IAHP by 95 +/- 5% (mean +/- SE), reduced the Ca2+ current by only 8 +/- 4%. 3. Activation of mGluRs accelerates the irreversible inhibition of IAHP that develops when 88 microM GTP-gamma-S is included in the pipette filling solution, whereas inclusion of 1 mM GDP-beta-S attenuated the inhibitory action of ACPD. These results indicate that the response to mGluR activation is G protein mediated. 4. Group I mGluRs, which includes mGluR1 and mGluR5, are G-protein-coupled receptors that are known to stimulate phospholipase C (PLC)-mediated hydrolysis of phosphoinositides to produce 1,4,5-triphosphate (IP3), which in turn is known to mobilize the release of intracellular Ca2+. The weak but selective mGluR1 agonist (S)-3-hydroxyphenylglycine (100 microM) completely inhibited IAHP, and the mGluR1 antagonist (S)-4-carboxyphenylglycine (500 microM) reduced IAHP inhibition produced by 5 microM ACPD from 73 +/- 6% to 22 +/- 4%. These results indicate that the mGluR responsible for IAHP inhibition has a similar pharmacological profile to that of those coupled to IP3 production. 5. The effects of agents known to interfere with IP3 production and action also support IP3 involvement in ACPD action. Neomycin (1 mM in pipette solution), which should reduce IP3 production through inhibition of PLC, reduced the ability of 10 microM ACPD to inhibit IAHP from almost 100% to 57 +/- 8% (n = 8). Heparin, an IP3 receptor antagonist that reduces Ca2+ mobilization, attenuated the inhibitory action 10 microM ACPD from almost 100% to 39 +/- 5% (n = 5). Heparin by itself increased the amplitude and duration of IAHP, suggesting that resting levels of IP3 are sufficient to suppress of IAHP partially. 6. In addition to the pool of intracellular Ca2+ that is mobilized by IP3, there is a distinct pool that is responsible for Ca(2+)-triggered Ca2+ release and is blocked by ryanodine or dantrolene. These drugs caused a small reduction of both IAHP and the inhibitory action of ACPD. Possibly the Ca2+ signal mobilized by IP3 is partially amplified by Ca2+ released from the ryanodine-sensitive stores. 7. Activation of PLC can also lead to the production of diacylglycerol and activation of protein kinase C (PKC). However, the inhibitory action of ACPD on IAHP was not affected by staurosporine at a concentration (1 microM) that inhibits both protein kinase A (PKA) and PKC and blocks the action of 5-HT to inhibit IAHP. 8. Activation of PKA by the adenylate cyclase activator forskolin led to inhibition of IAHP. Although activation of mGluR1 agonists can also stimulate adenylate cyclase and activate PKA, inhibition of PKA and the effect of forskolin on IAHP with the Walsh peptide did not affect ACPD inhibition of IAHP. 9. All of our results support the hypothesis that mGluR-mediated inhibition of IAHP is initiated by the production of IP3 and the mobilization of intracellular Ca2+.


Subject(s)
Calcium/physiology , Dentate Gyrus/physiology , Inositol 1,4,5-Trisphosphate/biosynthesis , Neurons/physiology , Potassium Channels/physiology , Receptors, Metabotropic Glutamate/physiology , Animals , Calcium/metabolism , Cyclic AMP-Dependent Protein Kinases/physiology , Cycloleucine/analogs & derivatives , Cycloleucine/pharmacology , Dentate Gyrus/cytology , GTP-Binding Proteins/physiology , Heparin/pharmacology , Male , Neomycin/pharmacology , Protein Kinase C/physiology , Rats , Rats, Wistar , Receptors, Metabotropic Glutamate/agonists
12.
J Physiol ; 496 ( Pt 1): 139-44, 1996 Oct 01.
Article in English | MEDLINE | ID: mdl-8910202

ABSTRACT

1. Activation of metabotropic glutamate receptors (mGluRs) inhibits a transient Ca(2+)-activated K+ current (IAHP) responsible for the slow after-hyperpolarization that follows depolarizations of dentate granule neurones in rat hippocampal brain slices. Here we show for the first time that this physiological consequence of mGluR stimulation is selectively attenuated by blockers of protein tyrosine kinases (PTKs). 2. Several distinct types of PTK blockers, including genistein, tyrphostin-B42 and lavendustin-A, reduced the inhibition of IAHP by the selective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD). Inhibition of IAHP by 5-HT was unaffected. The PTK blockers by themselves doubled the duration of IAHP suggesting that there exists a tonic inhibitory influence on IAHP that is reduced by PTK antagonists. 3. Inclusion of EGTA (1 mM) in the patch pipette also potentiated the IAHP and reduced the inhibitory action of ACPD on IAHP, consistent with the observation of others that chelation of intracellular Ca2+ prevents protein tyrosine phosphorylation induced by ACPD. 4. we propose that mGluR-initiated inositol 1,4,5-trisphosphate (InsP3) production mobilizes intracellular Ca2+ and leads to increased protein tyrosine phosphorylation which in turn leads to inhibition of IAHP.


Subject(s)
Calcium/physiology , Dentate Gyrus/metabolism , Neurons/metabolism , Potassium Channels/metabolism , Protein-Tyrosine Kinases/antagonists & inhibitors , Receptors, Metabotropic Glutamate/agonists , Adenylyl Cyclases/metabolism , Animals , Cycloleucine/analogs & derivatives , Cycloleucine/pharmacology , Dentate Gyrus/cytology , Dentate Gyrus/drug effects , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Genistein , In Vitro Techniques , Isoflavones/pharmacology , Male , Neuronal Plasticity/drug effects , Neuronal Plasticity/physiology , Neurons/drug effects , Neurotoxins/pharmacology , Potassium Channels/physiology , Rats , Rats, Wistar , Staurosporine/pharmacology
13.
J Physiol ; 495 ( Pt 1): 113-25, 1996 Aug 15.
Article in English | MEDLINE | ID: mdl-8866356

ABSTRACT

1. Whole-cell recording from pairs of adjacent mouse hippocampal neurons in culture was used to study the quantal properties of action potential-evoked excitatory synaptic transmission and to demonstrate the use of Sr2+ in quantifying those properties. 2. In the presence of extracellular Sr2+, excitatory postsynaptic currents (EPSCs) were followed by an after-discharge of miniature excitatory postsynaptic currents (mEPSCs) lasting 1-2 s and generated by evoked asynchronous release of presynaptic quanta of transmitter. Like the EPSC of which it is thought to be an extension, the after-discharge was modulated by procedures expected to modulate Sr2+ influx into the nerve terminal. The number of mEPSCs in the after-discharge was decreased by increasing extracellular [Mg2+], and increased by increasing extracellular [Sr2+] or increasing the number of action potentials used to evoke the after-discharge. 3. EPSCs recorded in media containing either 1 mM Ca2+ or 6 mM Sr2+ were of similar amplitude. Adding Sr2+ to low-Ca2+ media increased EPSC amplitude, while adding Sr2+ to high-Ca2+ media lowered EPSC amplitude. These results suggest that extracellular Sr2+ is less effective than Ca2+ in supporting quantal release. 4. The levels of extracellular Ca2+, Mg2+ and Sr2+ were adjusted so that most after-discharge mEPSCs were discrete and comparable in numbers to the quantal events that contributed to the corresponding evoked EPSCs. In a series of twenty-five pairs of neurons, the mean amplitude of mEPSCs recorded at -80 mV was 35 +/- 10 pA and the mean coefficient of variation was 0.50 +/- 0.10 (range, 0.26-0.62). The mEPSC amplitude histogram was positively skewed. 5. In ten pairs of neurons, the mean and variance of EPSCs and mEPSCs and quantal content were determined from samples of more than 100 evoked events (in superfusion solutions containing (mM): 0.5 Ca2+, 2 Sr2+ and 10 Mg2+) and mean quantal content was determined from the ratio of amplitudes of the mean EPSC and mEPSC. A binomial quantal analysis produced values of 2-12 for Napp (apparent number of independent synapses) and 0.25-0.75 for Papp (apparent probability of releasing a quantum at one of those synapses). These parameters predicted the number of observed failures. The observed coefficient of variation for quantal content predicted the observed coefficient of variation of the EPSC amplitude when the coefficient of variability of quantal amplitude of after-discharge mEPSCs was taken into account. 6. In six pairs of neurons, where more than 250 evoked events were recorded, the observed amplitude histogram for EPSCs could be approximated by a predicted amplitude distribution generated from the estimated binomial parameters and an empirical function describing the amplitude distribution of after-discharge mEPSCs. 7. The observation that parameters derived from mEPSCs that contribute to the Sr(2+)-generated after-discharge can predict the shape of the EPSC amplitude distribution and a quantal content consistent with the observed failure rate and EPSC amplitude variance, suggests that this subset of mEPSCs has the same properties as the quantal events released around the time of the peak of the corresponding EPSCs. The use of Sr2+ to evoke after-discharges of mEPSCs should allow unambiguous determination of the extent to which modification of synaptic strength is pre- or postsynaptic.


Subject(s)
Hippocampus/drug effects , Strontium/pharmacology , Synaptic Transmission/drug effects , Animals , Culture Techniques , Mice , Mice, Inbred Strains , Patch-Clamp Techniques
14.
J Neurosci ; 15(10): 6946-56, 1995 Oct.
Article in English | MEDLINE | ID: mdl-7472451

ABSTRACT

Small amplitude depolarizations (fast prepotentials, spikelets) recorded in mammalian neurons are thought to represent either dendritic action potentials or presynaptic action potentials attenuated by gap junctions. We have used whole-cell recordings in an in vitro calcium-free model of epilepsy to record spikelets from CA1 neurons of the rat hippocampus. It was found that spikelet appearance was closely correlated with the occurrence of dye coupling between pyramidal neurons, indicating that both phenomena share a common substrate. Spikelets were characterized according to waveform (amplitude and shape) and temporal occurrence. Spikelet amplitudes were found to be invariant with neuronal membrane potential, and their pattern of occurrence was indistinguishable from patterns of action potential firing in these cells. Voltage and current recordings revealed a spikelet waveform that was usually biphasic, comprised of a rapid depolarization followed by a slower hyperpolarization. Numerical differentiation of spike bursts resulted in waveforms similar to recorded spikelet sequences, while numerical integration of spikelets yielded waveforms that were indistinguishable from action potentials. Modification of spikelet waveforms by the potassium channel blocker tetraethylammonium chloride suggests that spikelets may arise from both resistive and capacitive transmission of presynaptic action potentials. Intracellular alkalinization and acidification brought about by perfusion with NH4Cl caused changes in spikelet frequency, consistent with reported alterations of field burst activity in this model of epilepsy. These results suggest that spikelets result from gap junctional communication, and may be important determinants of neuronal activity during seizure-like activity.


Subject(s)
Calcium/pharmacology , Cell Communication , Hippocampus/physiology , Neurons/physiology , Animals , Coloring Agents , Electrophysiology , Hippocampus/cytology , Hydrogen-Ion Concentration , In Vitro Techniques , Intracellular Membranes/metabolism , Neurons/drug effects , Rats , Rats, Wistar , Tetraethylammonium , Tetraethylammonium Compounds/pharmacology , Time Factors
15.
J Neurosci ; 14(7): 4308-17, 1994 Jul.
Article in English | MEDLINE | ID: mdl-8027781

ABSTRACT

To date, there is little experimental evidence supporting or refuting electrotonic interactions through gap junctions in the generation and/or spread of seizure activity in the mammalian brain. We have studied gap junctional mechanisms in the in vitro calcium-free induced model of epilepsy using electrophysiological and staining techniques in the CA1 area of the hippocampus. Lucifer yellow staining of CA1 pyramidal neurons revealed that dye coupling was increased 2.3 times in hippocampal slices made hyperexcitable by perfusion with calcium-free artificial cerebrospinal fluid (aCSF). Furthermore, multiple neuronal dye coupling (triplets, quintuplets) was observed in these conditions but never in control (standard aCSF). Under conditions that reduce gap junctional conductance (intracellular acidification, octanol, halothane), seizure-like activity was suppressed in the CA1 area in this epilepsy model, whereas increasing gap junctional conductance by intracellular alkalinization increased the frequency and duration of field burst events. Intracellular acidification also reduced dye coupling as well as the frequency of fast prepotentials (electrotonic potentials) without altering neuronal firing frequency. Simultaneous extracellular field and single whole-cell recordings revealed suppression of synchronization between neuronal firing and spontaneous field burst activity during acidification. These observations indicate an apparent increase in electrotonic coupling during calcium-free induced spontaneous rhythmic field burst activity in the CA1 area of the hippocampus and that electrotonic coupling may contribute substantially to the synchronization of neuronal firing underlying seizure-like events.


Subject(s)
Calcium/metabolism , Epilepsy/etiology , Gap Junctions/physiology , Hippocampus/physiopathology , Acids/pharmacology , Animals , Electrophysiology , Epilepsy/physiopathology , Fluorescent Dyes , Hippocampus/cytology , In Vitro Techniques , Isoquinolines , Neurons/physiology , Octanols/pharmacology , Rats , Rats, Wistar , Time Factors
16.
Brain Res ; 649(1-2): 305-9, 1994 Jun 27.
Article in English | MEDLINE | ID: mdl-7953646

ABSTRACT

Changes in voltage dependent calcium currents in the dentate gyrus of the hippocampal slice during ethanol withdrawal were studied using an alcohol withdrawal seizure prone mouse strain (WSP) and compared to a withdrawal-resistant strain (WSR). There was a significant increase in the high voltage activated calcium currents during the withdrawal period in the WSP strain, while those of the resistant strain showed no significant enhancement. These results suggest that an increase in calcium currents is one factor involved in the alcohol withdrawal hyperexcitability of the prone strain observed in vivo.


Subject(s)
Calcium Channels/metabolism , Ethanol/pharmacology , Hippocampus/metabolism , Substance Withdrawal Syndrome/metabolism , Animals , Hippocampus/cytology , Hippocampus/drug effects , In Vitro Techniques , Male , Mice , Mice, Inbred Strains , Neurons/drug effects , Neurons/metabolism , Patch-Clamp Techniques , Seizures/physiopathology , Species Specificity , Substance Withdrawal Syndrome/genetics
17.
Pflugers Arch ; 426(3-4): 247-53, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8183635

ABSTRACT

Using the whole-cell recording technique, we have examined the slow Ca(2+)-activated afterhyperpolarization (AHP) and its underlying current (IAHP) in hippocampal CA1 neurones of brain slices obtained from mature rats. Specifically we have studied the effects of the anion component of various K+ salts commonly used to make the pipette filling solution that dialyses neurones during whole-cell recordings. Among the K+ salts examined which included potassium methylsulfate, potassium methanesulfonate, potassium gluconate, potassium chloride, potassium citrate and potassium glutamate, stable AHPs/IAHP and strong spike firing adaptation could only be observed in neurones recorded with the patch pipette solution containing potassium methylsulfate. These AHPs and firing patterns closely mimicked those recorded with sharp electrodes. Similarly, the sustained component of voltage-activated Ca2+ currents was more stable in neurones dialysed with cesium methanesulfonate than in those dialysed with cesium gluconate or cesium chloride. Although the mechanisms underlying the interaction(s) between internally applied anions and ionic channels need further investigation, the present experiments illustrate that in mammalian brain neurones at 33 degrees C, the Ca(2+)-activated IAHP is dramatically altered by internal anions. We suggest that among anions commonly used in electrode filling solutions for whole-cell recordings, methylsulfate is the least disruptive to intracellular structures or Ca2+ homeostasis and permits stable whole-cell recording of the IAHP and Ca2+ currents in mammalian CNS neurones.


Subject(s)
Calcium/physiology , Hippocampus/physiology , Neurons/physiology , Animals , Anions/pharmacology , Chlorides/pharmacology , Citrates/pharmacology , Electrophysiology , Gluconates/pharmacology , Hippocampus/cytology , Hippocampus/drug effects , In Vitro Techniques , Membrane Potentials/drug effects , Microelectrodes , Neurons/drug effects , Rats , Rats, Wistar , Sulfuric Acid Esters/pharmacology
18.
J Neurophysiol ; 70(1): 223-31, 1993 Jul.
Article in English | MEDLINE | ID: mdl-8395576

ABSTRACT

1. The underlying ionic mechanisms of the postspike depolarizing afterpotential (DAP) in hippocampal dentate granule (DG) neurons of immature rats (postnatal 7- to 17-day-old) were examined using whole cell patch recordings in brain slices. 2. In current-clamp mode, the DAP followed each single action potential. Graded DAP-like responses were also evoked by depolarizing current pulses when the action potential was blocked by tetrodotoxin (TTX), demonstrating that the TTX-sensitive Na+ conductance is not necessary for DAP generation. The membrane resistance near the DAP peak was lower than at rest, suggesting activation of inward currents rather than blockade of outward currents during the DAP. The DAP peak amplitude showed a strong dependence on voltage, increasing with membrane hyperpolarization and decreasing with depolarization in the range of -90 to -50 mV. Repetitive stimulation at 1-2 Hz did not change the amplitude or decay of the DAP or DAP-like response. 3. Bath application of 2 mM 4-aminopyridine (4-AP) and 5 mM tetraethylammonium chloride (TEA) prolonged the action potential and enhanced the DAP, suggesting that the DAP waveform is determined by the interaction of voltage-activated outward K+ currents and inward currents. 4. Bath application of 2 mM Co2+ depressed the DAP and the DAP-like potential. Replacement of extracellular Ca2+ with Ba2+ potentiated the DAP. Intracellular Ca2+ chelation with the fast chelator, bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA), only slightly enhanced the DAP, suggesting that the DAP is not generated by inward currents activated secondary to Ca2+ influx.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Aging/physiology , Calcium Channels/physiology , Hippocampus/physiology , Neuronal Plasticity/physiology , Synaptic Transmission/physiology , 4-Aminopyridine/pharmacology , Animals , Animals, Newborn , Calcium Channel Blockers/pharmacology , Calcium Channels/drug effects , Culture Techniques , Electric Stimulation , Hippocampus/drug effects , Limbic System/drug effects , Limbic System/physiology , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Neural Pathways/drug effects , Neural Pathways/physiology , Neuronal Plasticity/drug effects , Potassium Channels/drug effects , Potassium Channels/physiology , Rats , Rats, Wistar , Synaptic Transmission/drug effects , Tetraethylammonium , Tetraethylammonium Compounds/pharmacology
19.
Alcohol Alcohol Suppl ; 2: 395-401, 1993.
Article in English | MEDLINE | ID: mdl-7748329

ABSTRACT

The ubiquitous role of calcium in ethanol actions measured electrophysiologically in central neurons is discussed. Acute ethanol administration to rat hippocampal neurons in vitro causes a hyperpolarization, increased AHPs, increased EPSPs and IPSPs, decreased modelled electronic interneuronal coupling, decreased high threshold Ca2+ currents, increased Ik, and increased synaptic GABAA currents. Alcohol withdrawal reverses some of these actions. Ca2+ is implicated in all of the above ethanol mediated effects.


Subject(s)
Calcium/metabolism , Ethanol/toxicity , Hippocampus/drug effects , Hippocampus/metabolism , Animals , Electrophysiology , Homeostasis , In Vitro Techniques , Male , Neurons/drug effects , Neurons/metabolism , Potassium Channels/drug effects , Potassium Channels/metabolism , Rats , Receptors, GABA-A/drug effects , Receptors, GABA-A/metabolism , Synaptic Transmission/drug effects
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