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I Soltesz

Publications and source records attributed to I Soltesz.

At least 37 records · Page 2Linked to original sources
PubMed1997

Instantaneous perturbation of dentate interneuronal networks by a pressure wave-transient delivered to the neocortex.

Whole-cell patch-clamp recordings and immunocytochemical experiments were performed to determine the short- and long-term effects of lateral fluid percussion head injury on the perisomatic inhibitory control of dentate granule cells in the adult rat, with special reference to the development of trauma-induced hyperexcitability. One week after the delivery of a single, moderate (2.0-2.2 atm) mechanical pressure wave to the neocortex, the feed-forward inhibitory control of dentate granule cell discharges was compromised, and the frequency of miniature IPSCs was decreased. Consistent with the electrophysiological data, the number of hilar parvalbumin (PV)- and cholecystokinin (CCK)-positive dentate interneurons supplying the inhibitory innervation of the perisomatic region of granule cells was decreased weeks and months after head injury. The initial injury to the hilar neurons took place instantaneously after the impact and did not require the recruitment of active physiological processes. Furthermore, the decrease in the number of PV- and CCK-positive hilar interneurons was similar to the decrease in the number of the AMPA-type glutamate receptor subunit 2/3-immunoreactive mossy cells, indicating that the pressure wave-transient causes injurious physical stretching and bending of most cells that are large and not tightly packed in a cell layer. These results reveal for the first time that moderate pressure wave-transients, triggered by traumatic head injury episodes, impact the dentate neuronal network in a unique temporal and spatial pattern, resulting in a net decrease in the perisomatic control of granule cell discharges.

Animals↗
PubMed1997

Slow kinetics of miniature IPSCs during early postnatal development in granule cells of the dentate gyrus.

Whole-cell patch-clamp recordings were used to investigate the properties of GABAA receptor-mediated postsynaptic currents during development in dentate gyrus granule cells from neonatal [postnatal day 0 (P0)] to adult rats in brain slices. The frequency of miniature IPSCs (mIPSCs) was low at birth and increased progressively with age. The mIPSCs of all ages could be satisfactorily fitted with the sum of a single exponential rise and single exponential decay. From P0 to P14, both the rise time and the decay time constants were significantly longer than in the adult. The mIPSC rise and decay kinetics did not change during the first 2 postnatal weeks, but during the third week the kinetics sped up and by P21 attained adult values. In contrast, the amplitude of the mIPSCs did not change during development. The synaptic GABAA receptors in immature and adult cells showed differential sensitivity to modulators. The subunit-specific benzodiazepine agonist zolpidem increased the decay time constant of the IPSCs of immature granule cells with a reduced potency compared with the adult. Furthermore, zinc decreased the amplitude and decay time constant of mIPSCs from developing granule cells, whereas it had no effect on mIPSCs in adult neurons. The results reveal for the first time that until the end of the second postnatal week the synaptic GABAA receptor-mediated currents in dentate granule cells display slower rise and decay kinetics but similar amplitudes compared with adult, resulting in a net decrease in synaptic charge transfer during development.

Aging↗
PubMed1996

Neuroprotection by propofol in acute mechanical injury: role of GABAergic inhibition.

1. Whole cell patch-clamp and extracellular field recordings were obtained from granule cells of the dentate gyrus in 400-microns-thick brain slices of the adult rat to determine the actions of the intravenous general anesthetic 2,6-diisopropylphenol (propofol) on acute neuronal survival and preservation of synaptic integrity after amputation of dendrites (dendrotomy), and to determine the role of gamma-aminobutyric acid-A (GABAA)-receptor-mediated inhibition in the neuroprotective effects of propofol. The actions of propofol were compared with those exerted by another widely used intravenous general anesthetic, 5-ethyl-5-[1-methylbutyl]-2-thiobarbituric acid (thiopental). 2. Propofol (10 microM) increased the frequency (control: 5.9 +/- 0.9 Hz, mean +/- SE; propofol: 10.5 +/- 1.3 Hz) and the single-exponential decay time constant (tau D) (control: 4.5 +/- 0.2 ms; propofol: 15.3 +/- 1.5 ms) of miniature inhibitory postsynaptic currents (mIPSCs) recorded in control neurons. Thiopental (25 microM) also increased the tau D (14.3 +/- 0.9 ms) of mISPCs, but had no effect on mIPSC frequency. Both anesthetics potentiated mIPSCs at low concentrations (propofol: 5 microM; thiopental: 1 microM). Propofol and thiopental did not change the peak amplitude and rise times of mIPSCs. 3. Propofol (10 microM) was able to depress the excitability of control granule cells, as determined by the reduction in the amplitude of the orthodromic population spikes. This depression could be prevented by the GABAA receptor antagonist bicuculline (50 microM), indicating that propofol reduces excitability via GABAA receptor functions. 4. Propofol and thiopental were neuroprotectant (assessed by antidromic population responses 2-5 h after injury) if present before and during the amputation of the granule cell dendrites. The protective actions were dose dependent, and at high doses (propofol: 200 microM; thiopental: 400 microM) the anesthetics were as neuroprotective against dendrotomy-induced cell death as 2-amino 5-phosphovaleric acid (APV) and 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX). The protective effects of the anesthetics were completely blocked with the GABAA receptor antagonists picrotoxin or bicuculline, and were mimicked by the GABAA receptor agonist muscimol (100 microM). 5. Propofol, in contrast to APV and CNQX, could not prevent the dendrotomy-induced Ca(2+)-dependent and long-lasting changes in mIPSC decay kinetics (appearance of a double-exponential, prolonged decay). 6. The protective effects of the anesthetics and those of APV and CNQX on neuronal survival were not significant when the drugs were applied after dendrotomy, indicating that dendrotomy carried out 150-200 microns from the soma without neuroprotective agents rapidly induces irreversible acute degeneration in most injured neurons. The failure to rescue cells from dendrotomy-induced injury did not result from a decreased sensitivity of the GABAA receptors to the anesthetics, because the potentiating effects of the anesthetics on mIPSCs from control and dendrotomized neurons were not different. 7. These data indicate that propofol potentiates synaptic inhibition pre- and postsynaptically, and, when present during dendrotomy, it can protect neurons from acute mechanical-injury induced cell death via potentiation of GABAA receptor functions. However, propofol fails to provide neuroprotection against dendrotomy-induced changes in synaptic physiology.

Acute Disease↗
PubMed1995

Tonic inhibition originates from synapses close to the soma.

Central neurons are subject to a tonic barrage of randomly occurring spontaneous inhibitory events (mIP-SCs) resulting from the action potential-independent release of gamma-aminobutyric acid (GABA). Do the terminals making synapses onto somatic versus dendritic sites, which arise from specific populations of interneurons, differ in their ability to generate mIPSCs? We have combined the techniques of whole-cell patch-clamp recording and computational simulation to demonstrate that in granule cells of the dentate gyrus, most of the action potential-independent inhibition taking place as mIPSCs originates from proximal sites. Indeed, removal of the bulk (> 50%) of the dendritic tree did not change the characteristics of mIPSCs. These results are consistent with a functional segregation of GABAergic terminals synapsing at proximal versus distal portions of central neurons. Thus, proximal GABAergic terminals are responsible for tonic inhibition targeted at the soma.

Action Potentials↗
PubMed1995

Ca(2+)-dependent plasticity of miniature inhibitory postsynaptic currents after amputation of dendrites in central neurons.

1. The effects of cutting off the bulk (> 2/3) of the dendritic tree (dendrotomy) on GABAergic miniature inhibitory postsynaptic currents (mIPCSs) were studied in granule cells of the adult rat dentate gyrus in 400-microns-thick slices in vitro. 2. After dendrotomy carried out in warm (32 degrees C) control artificial cerebrospinal fluid (ACSF), only small antidromic population spikes could be evoked in the granule cell layer, and no viable whole cell recordings could be obtained. However, when dendrotomy was performed in cold (8-10 degrees C) control ACSF, the amplitude of the antidromic population spikes increased, and stable whole cell recordings became possible. 3. Whole cell recordings, with CsCl-filled pipettes, from granule cells dendrotomized in cold control ACSF, revealed significant alterations, lasting > 10 h, in the decay kinetics of mIPSACs. The change consisted of a calcium-dependent transformation of the normal, single exponential decay into a prolonged double exponential that effectively increased the charge transferred by the synaptic events (the total area of the currents) by 67%. When 30 mM 1,2 bis-(2-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) was included in the pipette, the changes in the mIPSCs decay kinetics could still be observed after dendrotomy, indicating that the maintenance phase of this plasticity did not depend on elevated intracellular calcium levels. 4. Viable whole cell recordings could also be obtained in dendrotomized granule cells when the amputation of dendrites was carried out at 32 degrees C after incubation for 2 h with the cell-permeant Ca2+ chelator, BAPTA-AM (50 microM), or the cutting process was done in an ACSF containing either a combination of excitatory amino acid receptor antagonists 2-amino-5-phosphonovaleric acid (APV; 25 microM) + 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM), a blocker of intracellular Ca2+ release dantrolene-Na (20 microM), or the voltage-gated Na+ channel blocker tetrodotoxin (TTX; 1 microM). 5. After dendrotomy in BAPTA-AM, APV + CNQX, APV + CNQX + TTX, and/or dantrolene, the changes in decay kinetics were prevented, indicating that a rise in intracellular Ca2+ concentration plays a pivotal role in this plasticity. 6. Computer simulations of mIPSCs suggested that changes in single channel kinetics alone can, in principle, account for the Ca(2+)-dependent changes in mIPSC decay kinetics. 7. These findings are consistent with a lasting Ca(2+)-dependent increase in gamma-aminobutyric acid-A (GABAA) receptor function in cells that survive physical injury to their dendrites.

Animals↗
PubMed1994

Rapid turnover rate of the hippocampal synaptic NMDA-R1 receptor subunits.

The decrease in the number of synaptic NMDA receptors produced by prior i.c.v. injections of antisense oligonucleotides was examined in the CA1 stratum radiatum of hippocampal slices. Isolated NMDA and AMPA receptor-mediated components of extracellular synaptic responses were compared in slices obtained from control animals and from animals treated for 48 h with an 18-mer phosphorothioate antisense oligodeoxynucleotide directed against NMDA-R1. In slices ipsilateral to the injected hemisphere, the synaptic NMDA component was decreased by 29% compared with the contralateral side and by 34% compared with animals injected with vehicle alone. At the same time, synaptic AMPA receptor-mediated components were not affected. These results are consistent with a rapid turnover rate of synaptic NMDA-R1 and demonstrate the feasibility of antisense oligonucleotide techniques for the depletion of specific synaptic receptor channels.

Animals↗
PubMed1994

Sensory input and burst firing output of rat and cat thalamocortical cells: the role of NMDA and non-NMDA receptors.

1. Intracellular and patch-clamp recordings were obtained from thalamocortical (TC) cells in the rat and cat dorsal lateral geniculate nucleus (dLGN) in vitro to study the role of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the synaptic potential and burst firing evoked by electrical stimulation of the optic tract. 2. At membrane potentials more positive than -65 mV, the sensory synaptic potential consisted of a fast EPSP that was followed by a smaller, slower component. At membrane potentials more negative than -65 mV, this slower component became more prominent owing to the presence of a low-threshold (LT) Ca2+ potential, which in turn evoked a high-frequency (> 150 Hz) burst of action potentials. The lower, but not the upper limit of the range of membrane potential over which burst firing occurred was dependent on the amplitude of the fast EPSP. 3. The non-NMDA receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM) and 1-(4-amino-phenyl)-4-methyl-7,8-methylene-dioxy-5H-2,3- benzodiazepine (GYKI 52466, 100 microM) greatly depressed the fast EPSP, abolished the burst firing generated by the LT Ca2+ potential, and left a relatively small, slow EPSP, which was sensitive to the NMDA antagonist DL-2-amino-5-phosphonovaleric acid (DL-AP5, 50-100 microM). 4. In the absence of CNQX or GYKI 52466, DL-AP5 depressed the slow but not the fast EPSP. DL-AP5 also increased the latency of the first action potential evoked by the LT Ca2+ potential or even abolished the LT Ca2+ potential and associated burst firing. The latter effect was only present when this type of firing occurred within a small membrane potential range. 5. DL-AP5 had no effect on the properties of the LT Ca2+ current IT, indicating that its effect on the burst firing was not mediated by a direct action on IT. 6. The response of TC cells to high-frequency (100 Hz) stimulation consisted of an initial burst firing response, followed by a sustained depolarization that could reach firing threshold. This sustained depolarization was markedly depressed by DL-AP5 but not by CNQX. 7. These results demonstrate that with low-frequency stimulation of the sensory afferents, the generation of TC cell output in the rat and cat dLGN is mainly controlled by non-NMDA receptors, while the contribution of NMDA receptors is limited to the burst firing generated by the LT Ca2+ potential, and depends on the membrane potential range over which this type of firing occurs.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1994

Bridging the cleft at GABA synapses in the brain.

A fragile balance between excitation and inhibition maintains the normal functioning of the CNS. The dominant inhibitory neurotransmitter of the mammalian brain is GABA, which acts mainly through GABAA and GABAB receptors. Small changes in GABA-mediated inhibition can alter neuronal excitability profoundly and, therefore, a wide range of compounds that clearly modify GABAA-receptor function are used clinically as anesthetics or for the treatment of various nervous system disorders. Recent findings have started to unravel the operation of central GABA synapses where inhibitory events appear to result from the synchronous opening of only tens of GABAA receptors activated by a saturating concentration of GABA. Such properties of GABA synapses impose certain constraints on the physiological and pharmacological modulation of inhibition in the brain.

Hippocampus↗
PubMed1994

Patch-clamp recordings reveal powerful GABAergic inhibition in dentate hilar neurons.

Whole-cell and cell-attached patch-clamp recordings were used to investigate the nature of GABAA receptor-mediated inhibition in the adult rat dentate gyrus in standard 400-microns-thick horizontal slices. In the presence of the glutamate receptor antagonists D-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, whole-cell voltage-clamp experiments with chloride-filled electrodes ([Cl-]in = [Cl-]out) revealed a high degree of spontaneous activity (10-60 Hz) in all hilar neurons (HNs) recorded with access resistances lower than 20 M omega. The events were inward at negative holding potentials, reversed at around the Cl- equilibrium potential, and were completely abolished by the specific antagonists of the GABAA receptor channel picrotoxin and SR-95531 in a reversible manner, indicating that they were spontaneous inhibitory postsynaptic currents (sIPSCs) mediated by GABAA receptors. The majority of the sIPSCs were TTX-insensitive miniature currents resulting from the action potential-independent release of GABA. The 10-90% rise times and the monoexponential decay time constants of the sIPSCs were significantly longer in HNs than those found in neighboring granule cells (GCs). Furthermore, the decay time constant of the hilar sIPSCs was not voltage dependent, contrary to the voltage dependency of the decay time constant of the sIPSCs recorded from GCs. As HNs have longer electrotonic length than GCs do, dendritic filtering may contribute to the kinetic differences. Non-stationary fluctuation analysis showed that whereas the number of channels open at the peak of individual sIPSCs was similar, the single-channel conductances significantly differed between the two cell groups. The 21% smaller single-channel conductance and the existence of electrotonically close GABAergic synapses on HNs indicate that dendritic filtering alone cannot explain the differences between HNs and GCs. The distinct subunit composition of the GABAA receptor channels in HNs and GCs may also be responsible for the altered kinetics of IPSCs in HNs. However, the subunit specific benzodiazepine agonist zolpidem (3 microns) prolonged the monoexponential decay time constants in both HNs and GCs. Thus, differences between the GABAA receptors of the two cell types are not due to a simple all-or-none presence/absence of the alpha 5 subunit.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1993

The behavior of mossy cells of the rat dentate gyrus during theta oscillations in vivo.

Intracellular current clamp recordings were obtained from mossy cells (n = 6, identified by intracellular injection of biocytin) of the dorsal dentate gyrus from rats under ketamine-xylazine anesthesia. During electroencephalographic theta rhythm (4-6 Hz), recorded with a macroelectrode placed in the contralateral dorsal hippocampus near the fissure, mossy cells displayed intracellular membrane potential oscillations at low frequencies (4-6 Hz) which appeared to be phase locked to the electroencephalographic theta rhythm. The frequency of the intracellular theta rhythm was independent of the membrane potential. However, the phase difference between the intracellular and the electroencephalographic theta rhythms as well as the amplitude of the intracellular theta oscillations were voltage-dependent. These findings are consistent with the hypothesis that rhythmic GABAA receptor-mediated inhibitory postsynaptic potentials contribute to the genesis of the intracellular theta rhythm. Indeed, mossy cells displayed an early, fast inhibitory postsynaptic potential in response to electrical stimulation of the entorhinal cortex, which most likely represents a GABAA receptor-mediated event, indicating that mossy cells possess functional GABAA receptors. At the resting membrane potential, mossy cells did not fire at each cycle of the electroencephalographic theta rhythm but fired only rarely (< 1 Hz). However, when they did fire they did so preferentially in phase with the peak positivity of the electroencephalographic theta rhythm. Reconstruction of two mossy cells with axonal projections to the inner molecular layer showed that the spatial extent of the influence such weakly discharging mossy cells may have on other dentate gyrus neurons during theta oscillations can be several millimeters in the septotemporal direction. In conclusion, these findings show that mossy cells of the rat hilus during ketamine-xylazine anesthesia participate in theta oscillations of the hippocampal formation, during which their low-frequency firing may contribute to the phase-locking of a large number of spatially distributed postsynaptic neurons with postsynaptic sites in the inner molecular layer of the dentate gyrus.

Animals↗
PubMed1993

Low- and high-frequency membrane potential oscillations during theta activity in CA1 and CA3 pyramidal neurons of the rat hippocampus under ketamine-xylazine anesthesia.

1. Intracellularly recorded low- and high-frequency (4-6 and 25-50 Hz, respectively), rhythmic, spontaneous membrane potential oscillations were investigated in pyramidal neurons of the rat hippocampus in vivo, during theta (theta, 4-6 Hz) electroencephalographic (EEG) activity, under ketamine-xylazine anesthesia. 2. The EEG activity showed two spectral peaks, one in the theta range, the other at higher frequencies (25-50 Hz). On the basis of their electrophysiological and pharmacological properties, it was concluded that the EEG theta-waves, and the fast EEG rhythm, recorded during ketamine-xylazine anesthesia, share the basic properties of those theta and fast rhythms that are recorded under the effects of other types of anesthetics. 3. When intracellular recordings (n = 32) were made with electrodes filled with potassium-acetate (K-acetate), the only CA1 and CA3 pyramidal cells (PCs) considered for further analysis were those that did not fire rhythmically at most or each cycle of the theta rhythm at the resting membrane potential. During EEG-theta, the membrane potential (Vm) of these cells showed a prominent oscillation (3-15 mV) with frequencies similar to those of the EEG-theta (the intracellular theta rhythm, intra-theta). 4. The frequency of the intra-theta was independent of the Vm. However, the phase difference between the intra-theta and the EEG-theta was voltage dependent in both types of cells. CA1 PCs showed a large (120-180 degrees, where 360 degrees is the full cycle), gradual shift in the phase difference between the intra-theta and the EEG-theta, when the membrane was hyperpolarized to -85 from -65 mV. Although CA3 PCs displayed a larger variability in their phase-voltage relations, a voltage-dependent phase shift (90-180 degrees) could be observed in CA3 PCs as well. 5. Although the amplitude of the intra-theta in both CA1 and CA3 PCs could display large, sudden, spontaneous changes at a given Vm, the amplitude-Vm plots tended to show a minimum between -70 and -80 mV. Spontaneous changes in the amplitude of the intra-theta did not affect the phase difference between the intra- and the EEG-theta rhythms. 6. Intracellular injection of QX-314 (50-100 mM) did not change the phase-Vm or the amplitude-Vm relationships of CA1 PCs. 7. Intracellular injection of chloride (Cl-) ions greatly reduced the voltage dependency of the phase difference and revealed fast (duration: 20-25 ms), depolarizing potentials (5-20 mV), which appeared at high frequencies (25-50 Hz), amplitude modulated at theta-frequencies.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia, General↗
PubMed1992

Detecting changes in neuronal activities induced by N-methyl-D-aspartate receptor blockade using non-linear dynamics techniques.

The dynamics of N-methyl-D-aspartate receptor blockade-induced transitions between two types of intracellularly recorded spontaneous membrane potential oscillation from cat thalamic neurons have been studied using non-linear dynamics techniques. We report that, as previously predicted by theoretical studies, the number of degrees of freedom of these oscillations (the minimal number of independent variables governing the activity) is small, i.e. they are low dimensional. The N-methyl-D-aspartate receptor antagonists DL-2-amino-5-phosphono-valeric acid and ketamine, which transformed one type of oscillation into another, decreased the calculated dimension. DL-2-Amino-5-phosphono-valeric acid had no effect on the dimension when Mg2+ was present in the perfusion medium. The decrease in dimension was gradual and its time-course had a sigmoidal shape. It is suggested that the application of the machinery of dynamical systems theory might help to detect and monitor drug-induced membrane potential state transitions and to identify the factors underlying membrane potential oscillations.

2-Amino-5-phosphonovalerate↗