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J J Hablitz

Publications and source records attributed to J J Hablitz.

At least 91 records · Page 5Linked to original sources

Effect of sodium ions on penicillin-induced epileptiform activity in vitro.

Intra- and extracellular recordings were obtained from the CA1 region of guinea pig hippocampal slices maintained in vitro. We studied the effect of reducing the extracellular sodium concentration on penicillin-induced epileptiform responses. In control experiments, Tris and choline were assayed as sodium substitutes. Choline was found unsuitable, since it induced repetitive firing in the absence of any convulsant agent. Replacement of 50% of the extracellular sodium ( [Na+]o) with Tris reduced the amplitude of the presynaptic fiber volley, the field EPSP, and the population spike. Intracellular studies showed that when [Na+]o was lowered, action-potential amplitudes were reversibly depressed by an amount close to that predicted by the Nernst relation. Orthodromically elicited epileptiform discharges, induced by penicillin, were reduced in a low-sodium medium when constant stimulus currents were employed. If orthodromic stimulus strengths in normal and low-sodium states were equated on the basis of the field-EPSP amplitude, no significant diminution of the depolarizing-wave component of the epileptiform response was observed. These results suggest that a synaptic component underlies penicillin-induced epileptiform discharges.

Animals↗

Excitation of hippocampal pyramidal cells by glutamate in the guinea-pig and rat.

1. The mechanism by which L-glutamic acid depolarizes hippocampal CA1 pyramidal neurones was investigated by using the in vitro slice and ionophoretic techniques. 2. Two types of responses were seen. One (in 85% of cells) consisted of spike discharges that outlasted the glutamate-induced depolarization. In the other (the rest of the cells), spikes were produced only during the rising phase of the depolarization. 3. The effect was highly localized; it disappeared when the ionophoretic electrode was moved vertically by as little as 20 micrometers. 4. The effect of glutamate persisted after synaptic transmission was blocked; this probably was due to a direct effect of glutamate on the cell membrane. 5. Small doses of glutamate produced either no change or an apparent increase in input resistance. With larger doses, the input resistance invariably decreased. The apparent increase in input resistance was not seen in cells treated with Mn2+ and TTX and is believed to be an effect of the depolarization rather than a direct effect of glutamate. 6. By extrapolation, the reversal potential for the glutamate response (EGlu) was found to -3.6 mV. 7. Following intracellular injection of Cs+, neurones could be depolarized to a range of +20 to +50 mV. The glutamate response could then be reversed. EGlu in these cells was -1.5 mV. 8. Using the Cs+-injection technique, it was also possible to reverse the e.p.s.p. E.e.p.s.p. was similar to EGlu. 9. When the external sodium concentration was reduced, the size of the glutamate response decreased, and EGlu became more negative.

Animals↗

Effects of intracellular injections of chloride and EGTA on postepileptiform-burst hyperpolarizations in hippocampal neurons.

Intracellular recordings were obtained from CA1 neurons of hippocampal slices maintained in vitro. Epileptiform activity was induced by bath application of either penicillin (3.4 mM) or picrotoxin (5 X 10(-4) M). The afterhyperpolarizations (AHPs) following evoked epileptiform events induced by penicillin were inverted by diffusion of chloride ions from KCl electrodes but were insensitive to injection of EGTA. Picrotoxin produced epileptiform events qualitatively similar to those seen with penicillin, but the AHPs were reduced or abolished by injection of EGTA and were chloride insensitive. AHPs that were evoked directly by depolarizing-current pulses when penicillin or picrotoxin was present were sensitive to EGTA. These results indicate that hippocampal CA1 neurons are capable of generating two types of hyperpolarizing events and that penicillin is apparently ineffective in completely blocking the chloride-mediated event.

Animals↗

Altered burst responses in hippocampal CA3 neurons injected with EGTA.

Intracellular injection of EGTA abolished the hyperpolarization seen after spontaneous and evoked bursts of action potentials in hippocampal CA3 neurons. Simultaneously recorded, orthodromically elicited IPSPs were relatively unaffected by this treatment. It is concluded that CA3 neurons generate at least two types of hyperpolarization: one resulting from a calcium-mediated potassium conductance and the other from increased conductance to chloride.

Animals↗

Endogenous nature of spontaneous bursting in hippocampal pyramidal neurons.

The normal spontaneous bursting behavior of hippocampal pyramidal neurons was investigated. Bursting frequency was found to be membrane potential dependent, the frequency increasing with maintained depolarization and decreasing upon hyperpolarization. Short depolarizing-current pulses would trigger bursts which outlasted the stimulus, and bursting continued when synaptic transmission had been blocked. The spontaneous bursts of these neurons, in contrast to bursts induced by convulsive agents, appear to exhibit the classical behavior of endogenous bursts as observed in invertebrate neurons. The endogenous bursts in hippocampal neurons may result, also, from an interplay of intrinsic membrane currents.

Action Potentials↗

Selective amplitude histograms: a statistical approach to EEG-single unit relationships in generalized epilepsy.

Statistical analysis techniques that permit detection and quantification of EEG-single unit correlations were employed in a study of generalized penicillin epilepsy in the cat. Single unit activity was recorded in cerebral and cerebellar cortices and compared to the locally recorded EEG. It was found that during generalized paroxysmal activity the background EEG was significantly related to the time of occurrence of unit discharge. The degree of synchrony of various units differed but tended to increase as the duration and extent of paroxysmal activity increased. These relationships were usually not evident upon visual inspection of the original unprocessed data but were consistently detected by the analysis techniques described here. The results demonstrate the usefulness of a statistical approach to the analysis of single unit data and suggest that, not only is there a significant relationship between paroxysmal events and neuronal activity in generalized penicillin epilepsy, but also an overall trend to closer synchronization of EEG and single unit discharges during nonparoxysmal periods.

Action Potentials↗

Chronically isolated cerebral hemisphere in the cat: effects of parenteral administration of penicillin.

Brain electrical activity (EEG) of cats with chronic, complete, neural isolation of the cortex of an entire cerebral hemisphere was studied prior to and following intramuscular administration of penicillin (250,000--300,000 units/kg). The most prominent feature of the isolated hemisphere's EEG during base-line recordings was irregular, aperiodic, slow-wave activity with intermittent sharp waves and occasional spike discharges. Following penicillin administration there was an increase in the number of spikes and sharp waves in the isolated hemisphere and an increase in amplitude of the background activity. Simultaneously recorded EEG activity of the intact hemisphere demonstrated the paroxysmal burts of sharp waves or spike-wave complexes that have been described previously in normal animals. There was complete independence of the electrical activity recorded from intact and isolated hemispheres. These results indicate that intramuscularly administered penicillin can exert a convulsant effect on cortical structures in the absence of subcortical connections, but the generalized epileptiform activity seen in normal animals is dependent on thalamocortical connections.

Animals↗

Cortical seizures following cerebellar stimulation in primates.

The effects of cerebellar stimulation were studied in monkeys with chronic alumina-cream epileptogenic foci in motor cortex. Low-frequency stimulation (5-15 c/sec) was ineffective in altering spontaneous cortical spiking. Clinical and electrographic seizures were elicited following high-frequency cerebellar stimulation (100 c/sec). This was a consistent finding following cerebellar stimulation, although no spontaneous seizures had been seen in these animals. These studies suggest the existence of facilitatory cerebellar mechanisms and indicate the need for further studies in chronic animal models.

Aluminum↗