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M J Gutnick

Publications and source records attributed to M J Gutnick.

At least 55 records · Page 3Linked to original sources
PubMed1982

Electrophysiological properties of neocortical neurons in vitro.

1. Intracellular recordings were obtained from neurons of the guinea pig sensorimotor cortical slice maintained in vitro. Under control recording conditions input resistances, time constants, and spiking characteristics of slice neurons were well within the ranges reported by other investigators for neocortical neurons in situ. However, resting potentials (mean of -75 mV) and spike amplitudes (mean of 93.5 mV) were 10-25 mV greater than has been observed in intact preparations. 2. Current-voltage relationships obtained under current clamp revealed a spectrum of membrane-rectifying properties at potentials that were subthreshold for spike generation. Ionic and pharmacologic analyses suggest that subthreshold membrane behavior is dominated by voltage-sensitive, very slowly inactivating conductances to K+ and Na+. 3. Action potentials were predominantly Na+ dependent under normal conditions but when outward K+ currents were reduced pharmacologically, it was possible, in most cells, to evoke a non-Na+-dependent, tetrodotoxin-(TTX) insensitive spike, which was followed by a prominent depolarizing after-potential. Both of these events were blocked by the Ca2+ current antagonists, Co2+ and Mn2+. 4. A small population of neurons generated intrinsic, all-or-none burst potentials when depolarized with current pulses or by synaptic activation. These cells were located at a narrow range of depths comprising layer IV and the more superficial parts of layer V. 5. Spontaneous excitatory synaptic potentials appeared in all neurons. Spontaneous inhibitory events were visible in only about 10% of the cells, and in those cases apparently reversed polarity at a level slightly positive to resting potential. Stimulation of the surface of the slice at low intensities evoked robust and usually concurrent excitatory and inhibitory synaptic potentials. Unitary inhibitory postsynaptic potentials (IPSPs) reversed at levels positive to rest. Stronger stimulation produced a labile, long-duration, hyperpolarizing IPSP with a reversal potential 15-20 mV negative to the resting level. 6. Neocortical neurons in vitro retain the basic membrane and synaptic properties ascribed to them in situ. However, the array of passive and active membrane behavior observed in the slice suggests that cortical neurons may be differentiated by specific functional properties as well as by their extensive morphological diversity.

Action Potentials↗
PubMed1982

Mechanisms of neocortical epileptogenesis in vitro.

1. The cellular mechanisms underlying interictal epileptogenesis have been examined in an in vitro slice preparation of guinea pig neocortex. Penicillin or bicuculline was applied to the tissue, and intracellular recordings were obtained from neurons and glia. 2. Following convulsant application, stimulation could elicit a short-latency excitatory postsynaptic potential (EPSP) and a large, longer latency depolarization shift (DS) in single neurons. DSs in neurons of the slice were very similar to those evoked in neurons of neocortex in vivo in that they displayed an all-or-none character, large shifts in latency during repetitive stimuli, long afterpotentials, and a prolonged refractory period. In contrast to epileptogenesis produced by penicillin in intact cortex, neither spontaneous DSs nor ictal episodes were observed in neocortical slices. 3. In simultaneous recordings from pairs of neurons within the same cortical column, DS generation and latency shifts were invariably synchronous. DS generation in neurons was also coincident with large, paroxysmal increases of extracellular [K+], as indicated by simultaneous recordings from glia. 4. When polarizing currents were applied to neurons injected with the local anesthetic QX-314, the DS amplitude varied monotonically and had an extrapolated reversal potential near 0 mV. In neurons injected with the K+-current blocker Cs+, large displacements of membrane potential were possible, and both the short-latency EPSP and the peak of the DS diminished completely at about 0 mV. At potentials positive to this, the short-latency EPSP was reversed, and the DS was replaced by a paroxysmal hyperpolarization whose rise time and peak latency were prolonged compared to the DS evoked at resting potential. The paroxysmal hyperpolarization probably represents the prolonged activation of the impaled neuron by EPSPs. 5. Voltage-dependent components, including slow spikes, appeared to contribute to generation of the DS at resting potential in Cs+-filled cells, and these components were blocked during large depolarizations. 6. The results suggest that DS generation in single neocortical neurons occurs during synchronous synaptic activation of a large group of cells. DS onset in a given neuron is determined by the timing of a variable-latency excitatory input that differs from the short-latency EPSP. The DS slow envelope appears to be generated by long-duration excitatory synaptic currents and may be modulated by intrinsic voltage-dependent membrane conductances. 7. We present a hypothesis for the initiation of the DS, based on the anatomical and physiological organization of the intrinsic neocortical circuits.

Animals↗
PubMed1982

Model for simulating cyclic variations in focal epileptogenic excitability.

During 0.2 to 1.0 Hz stimulation of an epileptogenic focus, the phenomenon of cyclic spike driving (CSD) occurs, wherein 20- to 40-sec active periods, in which each stimulus triggers an all-or-none interictal event (IE), alternate with quiet periods of similar duration, in which IE are not triggered. CSD was simulated by a model in which individual IE are followed by biphasic response functions which sum linearly to produce long-term oscillations of epileptogenic excitability relative to the IE triggering threshold. The model successfully simulates all of the major characteristics of experimentally induced CSD, including the effects of manipulating stimulus parameters. Results of the simulation provide clues as to the time course of mechanisms which control epileptogenic triggerability.

Action Potentials↗
PubMed1981

Dye-coupling between glial cells in the guinea pig neocortical slice.

Physiologically identified glial cells in guinea pig neocortical slices were injected with the low molecular weight, fluorescent dye Lucifer yellow CH. The stained aggregates which resulted consisted of one brightly stained, central cell surrounded by numerous lightly stained cells. The central cell had well defined feathery processes and resembled a protoplasmic astrocyte. The surrounding cells appeared also to be glial cells but lacked sufficient detail to be further categorized. This first demonstration of dye-coupling between neocortical glial cells strongly suggests that these cells are connected together via low resistance junctions capable of passing ionic current as well as dye.

Animals↗
PubMed1981

Extracellular potassium activity during frequency-dependent conduction block of giant axons in the metathoracic ganglion of the cockroach.

In the metathoracic ganglion (T3) of the cockroach, extracellular potassium activity (aK) was measured with ion-sensitive microelectrodes and intracellular recordings were simultaneously made from giant axons (GAs) during high frequency stimulation of the connectives. Blockade of spike conduction through T3 was associated with intraganglionic aK rises of 0.2-0.5 mM, which were only 10% of the periaxonal aK rises suggested from GA depolarizations. When aK in the bath was increased 10-fold, GA conduction block during 1 Hz stimulation did not occur until much higher levels of aK and GA depolarization were achieved. The results suggest that glial sheaths surrounding GAs significantly impede K+ movement, and may thus prevent non-specific axonal interactions, and that stimulus-induced conduction block is not primarily due to K+-induced depolarization and consequent Na+-inactivation.

Action Potentials↗
PubMed1981

Dye coupling and possible electrotonic coupling in the guinea pig neocortical slice.

Iontophoretic injection of the fluorescent dye Lucifer Yellow CH into single neurons of guinea pig neocortical slices resulted in the staining of more than one cell. Dye-coupled neuronal aggregates were found only in the superficial cortical layers and were often organized in vertical columns. Antidromic stimuli evoked all-or-none, subthreshold depolarizations in some superficial cells. These potentials were not eliminated by manganese and did not collide with spikes originating in the soma, suggesting that they arose from electrotonic interaction between superficial cortical neurons.

Action Potentials↗
PubMed1979

Stimulus induced and seizure related changes in extracellular potassium concentration in cat thalamus (VPL).

Extracellular potassium activity (ak) and field potentials (fp) were measured in the nucleus ventro-postero-lateralis (VPL) thalami in order to assess the extent of thalamic participation in cortical seizure activity. Small increases (up to 0.7 mmole/l) or decreases (up to 0.2 mmole/l) in ak were induced by electrical stimulation of the contralateral forepaw. These changes in ak were spatially more limited than the simultaneously recorded fp. Similar observations were made during weak electrical stimulation of the somatosensory cortex and during interictal spikes in a cortical penicillin focus. Large and widespread increases in ak to levels of 11.6 mmoles/l and slow negative fps of 8 mV accompanied seizure generation either in a cortical penicillin focus or during intense repetitive electrical stimulation of the cortical surface. Subsequent to such increases ak fell to subnormal levels. The amplitudes and durations of such undershoots were correlated with the amplitudes of the preceding increases in ak. Sometimes thalamic seizures ceases before cortical epileptic episodes. This resulted in a decrease of cortical EEG amplitudes. After ablation of the sensorimotor cortex seizures in forepaw-VPL could be induced by stimulation of the somatosensory cortex. These results further support the conclusion that specific thalamic nuclei participate in seizure generation and may serve as a subcortical route of seizure spread.

Afferent Pathways↗
PubMed1979

Relation between extracellular potassium concentration and neuronal activities in cat thalamus (VPL) during projection of cortical epileptiform discharge.

Neuronal and potassium activities (ak) were measured in the nucleus ventro-posterolateralis thalami (VPL) during propagated epileptiform activity from the somatosensory cortex of cats. Seizures were induced by repetitive electrical stimulation of the cortical surface or by topical application of penicillin. The recruitment of VPL into a seizure resulted in large increases of ak to levels of up to 11.6 mmoles/l, accompanied by increased in neuronal discharge rate to 300/sec. Sometimes the rise in ak preceded active participation of a given thalamo-cortical relay (TCR) neuron in the seizure. After reaching a peak level, ak and neuronal discharge rate slowly declined during an ictal episode. After cessation of seizures all TCR neurons were inhibited, while ak fell to subnormal levels. The duration of these postictal depressions increased with the amplitude of preceding increases and subsequent undershoots in ak and could last up to 120 sec. During decay and undershoot in ak, relay capability of TCR neurons was reduced. Also the probability that action potentials elicited in intracortical endings of TCR cells would antidromically invade their cell bodies was decreased. The duration of these periods varied with the amplitude of undershoot in ak. Seizure threshold was increased during undershoots. These observations are consistent with a long-lasting postictal hyperpolarization of neuronal membranes. The hyperpolarization may be caused by the action of an electrogenic pump, which is probably involved in termination of seizure discharge.

Animals↗
PubMed1977

Extracellular free calcium and potassium during paroxsmal activity in the cerebral cortex of the cat.

Extracellular calcium and potassium activities (aCa and aK) as well as neuronal activity were simultaneously recorded with ion-sensitive electrodes in the somatosensory cortex of cats. Baseline aCa was 1.2-1.5 mM/l, baseline aK 2.7-3.2 mM/l. Transient decreases in aCa and simultaneous increases in aK were evoked by repetitive stimulation of the contralateral forepaw, the nucleus ventroposterolateralis thalami and the cortical surface. Considerable decreases in aCa (by up to 0.7 mM/l) were found during seizure activity. A fall in aCa preceded the onset of paroxysmal discharges and the rise in aK after injection of pentylene tetrazol. The decrease in aCa led also the rise in aK during cyclical spike driving in a penicillin focus. It is concluded that alterations of Ca++ dependent mechanisms participate in the generation of epileptic activity.

Animals↗
PubMed1977

Iontophoretically applied corticosteroids do not affect the firing of hippocampal neurons.

In view of the possible role of the hippocampus in the neuroendocrine regulation of ACTH secretion, experiments were conducted in rats and cats in which cortisol (C) and corticosterone (CS) were applied by iontophoresis and pressure microinjection while recording from single identified pyramidal cells in the dorsal hippocampus, using multi-barrelled microelectrodes. None of the more than 500 cells tested responded with a significant change in firing rate. The possible relation of these findings to neuroendocrine regulation of ACTH secretion is discussed.

Action Potentials↗
PubMed1972

Thalamocortical relay neurons: antidromic invasion of spikes from a cortical epileptogenic focus.

Thalamocortical relay neurons whose axons project into a penicillininduced cortical epileptogenic focus generate bursts of action potentials during spontaneous interictal epileptiform discharges. These bursts originate in intracortical axons and propagate antidromically into thalamic neurons. Repetitive spike generation in cortical axons and presynaptic terminals could produce a potent excitatory drive and contribute to the generation of the large depolarization shifts which are seen in cortical elements during focal epileptogenesis.

Action Potentials↗