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M J Gutnick

Publications and source records attributed to M J Gutnick.

At least 37 records · Page 2Linked to original sources
PubMed1991

Chronic epileptic foci in neocortex: in vivo and in vitro effects of tetanus toxin.

Injection of 0.2 - 3.0 ng of tetanus toxin into rat parietal neocortex resulted in permanent (> 7 months) changes in the local circuit properties of this tissue. It caused excessive synchronization of neuronal activity. This was seen as spontaneous paroxysmal field potentials and/or evoked all-or-none population burst discharges. Such activity was recorded widely over the parietal and temporal areas of both the injected and the contralateral hemispheres from as little as 16 h after injection up to the maximum survival time of 7 months. Several observations suggest that the speed with which the hypersynchronous activity spread to the opposite hemisphere reflects transport of the toxin through corticocortical axons, and consequent blockade of synaptic inhibition. However, from what is known of the half life of the peptide in brain, it is unlikely that the persistent, widespread distribution of epileptiform discharge several months after injection was due to the continued presence of toxin. Thus, intracortical application of tetanus toxin provides a good experimental model of chronic focal epilepsies, and raises fundamental questions regarding the long term regulation of local circuit properties in the neocortex.

Journal Article↗
PubMed1991

Laminar distribution of neuronal membrane properties in neocortex of normal and reeler mouse.

1. Reeler is an autosomal recessive mutation of mice that alters neuronal migration during development, yielding a general inversion of the laminae in the neocortex. We recorded in vitro from slices of normal and reeler neocortex to study the influence of neuron position and shape on membrane properties and synaptic responses. 2. The intrinsic firing patterns, action-potential shapes, resting membrane potentials, input resistances, and evoked excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) did not differ between reelers and controls when data were grouped. 3. The depth distribution of intrinsic firing patterns was inverted in the reeler: intrinsically bursting (IB) neurons were found only in layer 5 in the normal mouse, but they were found exclusively in supragranular layers of the reeler cortex. 4. The spatial distribution of synaptic responses in the reeler was also inverted: very prominent IPSPs were characteristic of upper layer neurons in the normal mouse, but in the reeler similar inhibitory responses were observed predominantly in deep infragranular layers. 5. Dye injections in reeler pyramidal neurons revealed atypical morphologies, including distorted apical dendrites and cell inversion. 6. The data imply that cortical neurons develop the membrane and synaptic properties appropriate to their function, despite being malformed and mispositioned.

Animals↗
PubMed1990

Pentylenetetrazole-induced kindling is prevented by prior treatment with cysteamine.

We have previously demonstrated that in pentylenetetrazole (PTZ)-kindled rats, cysteamine causes prolonged depression of the kindled state. We now report that administration of cysteamine before or during the kindling process prevents attainment of the kindled state. This effect lasts long after cysteamine administration has ceased, suggesting that depletion or somatostatin may not be the only mechanism underlying cysteamine's effect on kindling. The results also support the likelihood that PTZ kindling primarily effects neocortical rather than limbic structures.

Animals↗
PubMed1990

Intrinsic firing patterns of diverse neocortical neurons.

Neurons of the neocortex differ dramatically in the patterns of action potentials they generate in response to current steps. Regular-spiking cells adapt strongly during maintained stimuli, whereas fast-spiking cells can sustain very high firing frequencies with little or no adaptation. Intrinsically bursting cells generate clusters of spikes (bursts), either singly or repetitively. These physiological distinctions have morphological correlates. RS and IB cells can be either pyramidal neurons or spiny stellate cells, and thus constitute the excitatory cells of the cortex. FS cells are smooth or sparsely spiny non-pyramidal cells, and are likely to be GABAergic inhibitory interneurons. The different firing properties of neurons in neocortex contribute significantly to its network behavior.

Animals↗
PubMed1989

Electrophysiological characteristics of neurons in neocortical explant cultures.

We examined the electrophysiological and morphological properties of neocortical neurons maintained in explant cultures prepared from the parietal cortex of newborn Sprague-Dawley rats. After 3-6 weeks in vitro, cultures showed regional differences in cellular density reminiscent of cortical layering, and an abundance of axonal processes. Pyramidal-shaped neurons with spinous dendrites were the dominant elements revealed by Lucifer yellow injections. Intracellular recordings revealed that many electrophysiological properties of neurons in the explants resembled those of neocortical neurons in vivo and in slice preparations. In response to depolarizing current injection, neurons in the explants showed the same three patterns of repetitive firing described in neocortical slices, as well as a similar array of responses. Spontaneous synaptic potentials were recorded from all neurons and complex PSPs were evoked in response to focal extracellular stimulation. GABAa receptors mediated a significant component of the evoked responses. Fifteen of sixty neurons generated action potentials that arose spontaneously from resting potentials. Neurons in many slices generated large, prolonged depolarizing potentials that reflected coordinated synaptic activity within the explants. These results underscore the usefulness of the neocortical explant as a valuable model for studying aspects of the behavior of circuits of cortical neurons.

Action Potentials↗
PubMed1989

Synchronized neuronal activities in neocortical explant cultures.

Intracellular recordings revealed that in neocortical explant cultures prepared on the day of birth and examined 3-6 weeks later, neurons mature and establish complex synaptic relationships that lead to spontaneous and triggered synchronous discharge. The spontaneous synchronous activity took several forms, including periodic generation of epileptiform depolarizing waves, prolonged periods of seizure-like discharge, and periodic, intense barrages of IPSPs. Synchronous depolarizations were associated with a marked increase in membrane conductance. Intracellular injection of currents of varying polarity and intensity affected their amplitudes and polarities without influencing the probability of their occurrence, indicating that the discharge reflected the synchronous activities of a neuronal population. This conclusion was confirmed with simultaneous recordings from pairs of neurons. Effects of the GABAa receptor antagonist, bicuculline, and the NMDA receptor antagonist, 2-aminophosphonvalerate (2APV), were used to assess the contributions of impairment of inhibition and enhancement of excitation to the initiation of synchronous discharge. The frequency with which spontaneous depolarizations were generated in normal medium was markedly reduced by 2APV. Moreover, seizure-like activity was induced by removing Mg++ from the medium, a condition that enhances conductance through NMDA receptor-coupled channels. This behavior was also attenuated by 2APV. Perfusion of bicuculline was potently epileptogenic. 2APV cut short the late, voltage-dependent phase of bicuculline-induced paroxysmal depolarizations, indicating a role of NMDA receptors in generating this component of the wave. Epileptiform activities induced by withdrawal of Mg++ were greatly augmented by bicuculline, indicating that blockade of inhibition was not a prerequisite for seizure-like activity. This conclusion is supported by the finding that in many neurons in untreated cultures, paroxysmal generation of trains of IPSPs was the primary manifestation of spontaneous, synchronous population discharge.

2-Amino-5-phosphonovalerate↗
PubMed1989

Low threshold calcium spikes, intrinsic neuronal oscillation and rhythm generation in the CNS.

Field potential studies in vivo have shown that many subcortical structures, such as the inferior olivary nucleus, the thalamic nuclei and the lateral habenular nucleus, generate behaviorally relevant rhythms. In each region, intracellular analysis in brain slices has revealed that activation of a transient, low-threshold calcium current plays a pivotal role in rhythmogenesis. The membrane potential of each individual neuron may oscillate rhythmically as a result of interplay between this current and other inward and outward voltage and calcium-dependent currents. Synchronization of this oscillatory single-cell activity, through mutual interaction and/or appropriately timed afferent drive, results in generation of stereotyped population rhythms.

Action Potentials↗
PubMed1989

Voltage-dependent and calcium-dependent inactivation of calcium channel current in identified snail neurones.

1. The dependence of Ca2+ current inactivation on membrane potential and intracellular Ca2+ concentration ([Ca2+]i) was studied in TEA-loaded, identified Helix neurones which possess a single population of high-voltage-activated Ca2+ channels. During prolonged depolarization, the Ca2+ current declined from its peak with two clearly distinct phases. The time course of its decay was readily fitted by a double-exponential function. 2. In double-pulse experiments, the relationship between the magnitude of the Ca2+ current and the amount of Ca2+ inactivation was not linear, and considerable inactivation was present, even when conditioning pulses were to levels of depolarization so great that Ca2+ currents were near zero. Similar results were obtained when external Ca2+ was replaced by Ba2+. 3. In double-pulse experiments, hyperpolarization during the interpulse interval served to reprime a portion of the inactivated Ca2+ current for subsequent activation. The extent of repriming increased with hyperpolarization, reaching a maximum between -130 and -150 mV. The effectiveness of repriming hyperpolarizations was considerably increased when Ca2+ was replaced by Ba2+. 4. A significant fraction of inactivated Ca2+ channels can be recovered during hyperpolarizing pulses lasting only milliseconds. If hyperpolarizing pulses were applied before substantial inactivation of Ca2+ current, Ca2+ channels remained available for activation despite considerable Ca2+ entry. 5. The relationship between [Ca2+]i and inactivation was investigated by quantitatively injecting Ca2+-buffered solutions into the cells. The time course of Ca2+ current inactivation was unchanged at free [Ca2+] between 1 x 10(-7) and 1 x 10(-5) M. From 1 x 10(-7) to 1 x 10(-9) M, inactivation became progressively slower, mainly due to a decrease of the amplitude ratio (fast/slow) of the two components of inactivation, which fell from about unity to near zero at 1 x 10(-9) M. In double-pulse experiments, recovery from inactivation was enhanced in neurones that had been injected with Ca2+ chelator. 6. We conclude that inactivation of Ca2+ channels in these neurones depends on both [Ca2+]i and membrane potential. The voltage-dependent process may serve as a mechanism to quickly recover inactivated Ca2+ channels during repetitive firing despite considerable Ca2+ influx. 7. The results are discussed in the framework of a model which is based on two states of inactivation, INV and INCA, which represent different conformations of the inactivating substrate, and which are both reached from a lumped state of activation (A). Inactivation leads to high occupancy of INV during depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Electrophysiological properties of neurons in the lateral habenula nucleus: an in vitro study.

1. The electroresponsive characteristics of neurons in the lateral habenula were studied with intracellular recordings in a brain slice preparation of guinea pig diencephalon maintained in vitro. One hundred and two neurons met the criteria for recording stability, and of these, 18 were analyzed in detail. For these 18 neurons, the mean resting membrane potential was -61.9 mV, the mean input resistance was 124 M omega, and the mean spike amplitude of fast action potentials was 60.3 mV. 2. Lateral habenula neurons were found to have distinct patterns of activity dependent on membrane potential. At membrane potentials more positive than -65 mV, depolarization elicited trains of sodium-dependent fast action potentials. At membrane potentials more negative than -65 mV, slight depolarization elicited a tetrodotoxin-insensitive wave of depolarization, called a low-threshold spike (LTS), from which a burst of fast action potentials were triggered. The principal conductance underlying the LTS is a low-threshold calcium conductance, which is inactivated at membrane potential more positive than -65 mV and deinactivated when the membrane is hyperpolarized to potentials more negative than -65 V. 3. Upon termination of injected hyperpolarizing current, many neurons displayed oscillation in membrane potential at a frequency of 3-10 Hz, thereby generating repetitive bursts of fast spikes. 4. The pattern of neuronal activity in lateral habenula neurons was highly sensitive to slight alterations in membrane potential. The ability of these neurons to fire action potentials in two modes, tonically and in bursts, and the propensity of these neurons to dramatically alter their output in response to transient hyperpolarizing input, indicate that transmission through this relay in the dorsal diencephalic conduction system may be greatly augmented by relatively small hyperpolarizing influences on the individual neurons.

Action Potentials↗
PubMed1987

Low-threshold calcium electrogenesis in neocortical neurons.

In slices of parietal neocortex, evidence was obtained for the existence of a low-threshold Ca2+ conductance in most neurons. This conductance became apparent when resting membrane potential was held below -60 mV by continuously injected, depolarizing current. Under these conditions, brief hyperpolarizing pulses were followed by generation of tetrodotoxin (TTX)-resistant, Mn2+-sensitive, low-threshold spikes. The results suggest that in neocortex, as in many subcortical structures, low-threshold Ca current may be responsible for burst generation in some neurons.

Animals↗
PubMed1987

Expression of rat brain excitatory amino acid receptors in Xenopus oocytes.

Xenopus laevis oocytes when injected with rat brain mRNA synthesize neuronal receptors that can be analyzed electrophysiologically. After a post-injection incubation period of 24-72 hours, L-glutamic acid, kainic acid and quisqualic acid caused a dose dependent (10-100 microM) depolarization of the oocyte membrane. The voltage and conductance changes associated with kainate activation were distinguishable from those seen for L-glutamate or quisqualate. There was no response to L-aspartate application and an inconsistent response to N-methyl-D-aspartate. Upon fractionation of the mRNA on sucrose gradients, transcripts greater than 2 Kb in length were obligatory for the synthesis of excitatory amino acid receptors. The electrophysiological response of injected oocytes exposed to L-glutamate was similar to that of native oocytes when exposed to muscarinic agents. This similarity may reflect the activation of the same ionophore and suggests that the active mRNA fraction for glutamate responsiveness either encodes for a binding protein that can be assembled along with native ion channels into the oocyte membrane or encodes for a glutamate binding site with a similar channel.

Amino Acids↗
PubMed1986

An N-methyl-D-aspartate (NMDA) receptor antagonist reduces bicuculline-induced depolarization shifts in neocortical explant cultures.

We investigated the actions of a specific N-methyl-D-aspartate (NMDA) antagonist, 2-amino-5-phosphonovaleric acid (2-APV), on bicuculline-induced epileptogenesis in organotypic explant cultures from neonatal rat neocortex. Explants were maintained in roller tubes for 3-5 weeks. The late, plateau phase of the intracellularly recorded paroxysmal depolarization shift was sensitive to both intracellularly injected hyperpolarizing currents and 2-APV, suggesting that this component is generated by a voltage-dependent, regenerative process that is mediated by activation of NMDA receptors. The results support the hypothesis that NMDA receptors play an important role in the generation of epileptiform activity by localized circuits of neocortical neurons.

2-Amino-5-phosphonovalerate↗
PubMed1985

Incidence of neuronal dye-coupling in neocortical slices depends on the plane of section.

The fluorescent dye Lucifer Yellow CH was intracellularly injected into neurons in slices of guinea-pig visual neocortex which had been prepared by sectioning either in a plane normal to the pial surface (radial slices) or in a plane parallel to the pial surface (tangential slices). In radial slices 44.3% of the injections resulted in dye-coupling and the number of cells coupled to the impaled neuron per injection followed a Poisson distribution. In contrast dye-coupling was not observed in tangential slices. Incidence of dye-coupling in slices that had been sectioned in both the radial and tangential planes was the same as in intact radial slices, indicating that slicing in the radial plane induced the formation of pathways for dye movement between neurons. The results suggest that formation and/or strengthening of direct intercellular junctions between neocortical neurons may occur as a specific neuronal response to partial dendrotomy.

Animals↗
PubMed1984

Cysteamine suppresses kindled seizures in pentylenetetrazol-kindled rats.

Rats were kindled by intraperitoneal injection of pentylenetetrazol (PTZ) (30 mg/kg) every 48 h. Once kindled, animals received a single injection of cysteamine (200 mg/kg) and subsequent responses to PTZ were observed. Cysteamine, an agent which depletes brain somatostatin and suppresses kindled seizures in amygdaloid-kindled rats, markedly suppressed the severity of PTZ-induced seizures in PTZ-kindled rats as well. However, it did not alter the convulsive response of non-kindled rats to a submaximal convulsive dose (50 mg/kg) of PTZ. The results support a role for somatostatin in kindling.

Animals↗
PubMed1983

Carbon dioxide uncouples dye-coupled neuronal aggregates in neocortical slices.

Lucifer Yellow was injected intracellularly into neurons in slices of guinea pig visual cortex. Dye coupling incidence was significantly decreased in slices that were incubated in a high concentration of carbon dioxide. This effect was probably due to intracellular acidification, since exposure to impermeant acid was not effective. The data are consistent with the hypothesis that carbon dioxide interferes with dye coupling in neocortex through its known action as an uncoupler of electronic coupling through gap junctions.

Animals↗
PubMed1982

Activity-dependent K+ accumulation in the developing rat optic nerve.

Potassium-sensitive microelectrodes were used to study activity-dependent changes of extracellular potassium ion concentration ([K+]o) in rat optic nerves of different postnatal ages (1 day to adulthood). The maximum level to which [K+]o rose with optimal frequencies of stimulation depended on age: mean maximum evoked [K+]o was 17.2 microM in 1- to 3-day-old optic nerves and 9.8 microM in adult nerves. The ceiling [K+]o seen in immature optic nerves, which is uniquely large for a mammalian central nervous system structure, may result from a relatively enhanced rate of evoked K+ release.

Aging↗