A. Lehmenkühler

Electrogenesis of Cortical DC Potentials

Publisher Summary This chapter discusses electrogenesis of cortical DC potentials. In accordance with earlier suggestions the term “DC potentials” is used to characterize the whole frequency range of extracellular field potentials that are reliably recorded by means of DC registration techniques. With this definition DC potentials comprise sustained shifts and slow fluctuations as well as faster waves superimposed on deviations of the baseline. The various forms of event-related potentials that are dealt with in subsequent presentations and discussions can therefore be classified as special subtypes of DC potentials. The question is where and how DC field potentials recorded, for instance, from the scalp are generated. Compared to an analysis of the conventional EEG, studies on generator structures and mechanisms of DC potentials meet with additional difficulties. A severe problem is that sustained or slowly changing DC potentials can originate, in principle, from a variety of generators. The role played by neurons as DC potential generators seems of particular interest.

Electrogenesis of Slow Potentials of the Brain

The occurrence of slow fluctuations down to 0 Hz in the spectrum of EEG waves has been known since the early days of electroencephalography, when the bioelectric activity of the brain was recorded by means of galvanometers (cf. Brazier, 1963; O’Leary & Goldring, 1976). However, such measurements were frequently distorted by uncontrollable artifacts due, for instance, to changes in electrode potentials or in skin resistance. As a result, the origin and functional significance of slow potential fluctuations in the cerebral cortex attracted little attention for rather a long time, and only a few decades later did essential improvements in the available technical equipment lead to more intense studies on the problem (cf. O’Leary & Goldring, 1964). The observed “slow” bioelectric phenomena were most often labeled “slow potentials,” “ultraslow oscillations,” or “steady (standing, sustained) potentials.” A common feature of all these fluctuations in the frequency range between approximately 0.5 and 0 Hz is that they can reliably be recorded only by means of DC amplifiers. To avoid confusion, it has therefore been proposed that the potential changes in question be referred to as “DC potentials” (Caspers, 1974). This term will be used also in this paper, and the following presentation will not be restricted to the origin of slow potentials encountered in definite experimental situations, but will deal with the problem on a more general basis.

Spreading depression can be restricted to distinct depths of the rat cerebral cortex

In cerebral cortex of rats recurrent and single spreading depressions (SDs) were elicited by KCl application and by needle prick, respectively. SDs were monitored by recording changes of DC (direct current) potentials and of K+ concentration ([K+]o) in the extracellular space using K(+)-selective microelectrodes. Profiles of DC potential and of [K+]o were obtained by stepwise lowering a microelectrode array consisting of up to four electrodes into the brain cortex. Recurrent SDs propagating from the site of KCl application had lower frequencies and longer duration in superficial compared to deeper cortical structures. Single SD elicited by needle prick 3 mm away from the recording sites usually invaded the whole grey matter and showed DC potential shifts that differed in shape from the recurrent SDs. At a depth restricted to 1000 microns SD-related DC potential shifts and rises in [K+]o were drastically diminished. In 2 of 8 experiments prick-elicited SD was absent either above or below cortical depths of 800-1000 microns. The results suggest a barrier for vertical SD propagation in cortical depth between 800 and 1200 microns. The observations are relevant for application of noninvasive techniques (DC electroencephalography, magnetoencephalography) to detect SD in the brain.

Caffeine-induced epileptic discharges in CA3 neurons of hippocampal slices of the guinea pig

In order to analyze the elementary mechanisms underlying caffeine-induced epileptiform discharges, hippocampal slices of guinea pigs were exposed to this drug. When the bath concentration of caffeine exceeded 0.2 mM, periodically occurring paroxysmal depolarizations (PD) in CA3 neurons appeared. They were accompanied by declines of extracellular free calcium concentration and were suppressed by the organic calcium antagonists verapamil and flunarizine. PD-like fluctuations of the membrane potential could be evoked also in CA3 neurons functionally isolated by tetrodotoxin (TTX). The observations indicate that caffeine-induced PD are generated endogenously and that transmembranous calcium currents contribute to these mechanisms.

Threshold extracellular concentration distribution of penicillin for generation of epileptic focus measured by diffusion analysis

The tissue volume required to produce a penicillin-induced interictal discharge in the local EEG was estimated. A pair of microelectrodes were lowered into the motor cortex of anaesthetised and artificially ventilated rats. One double-barrelled electrode was used to release tetramethylammonium (TMA+) by iontophoresis or to pressure eject a solution containing penicillin (PEN-) and TMA+ concentration. The extracellular distribution of PEN- was defined using diffusion analysis of the TMA+. From these data the spatial distribution of PEN- was estimated at the times of first interictal spikes in the EEG. The critical mass of active nerve cells was calculated from the threshold concentration of PEN- needed to elicit paroxysmal depolarisation shifts in neocortical slices and found to lie within a tissue sphere with a radius of ca. 150 microns.

Diffusion of penicillin in agar and cerebral cortex of the rat

The diffusion of penicillin was studied in agar gel and the cerebral cortex of the rat using pressure microinjection and ion-selective microelectrodes selective to penicillin. From the agar measurements a free diffusion coefficient for penicillin of 3.52 +/- 0.08 (mean +/- S.E.M.) X 10(-6) cm2.s-1 for 37 degrees C was determined. The tortuosity value in the cortex was 1.62 +/- 0.03 (mean +/- S.E.M.) at the same temperature implying an apparent diffusion coefficient of 1.34 +/- 0.07 (mean +/- S.E.M.) x 10(-6) cm2.s-1. This tortuosity value means that penicillin diffuses in the cortex in a similar manner to other extracellular substances. These diffusion values clarify previous estimates and permit accurate evaluation of epilepsy models based on the application of penicillin.

Extracellular changes of inorganic phosphate are different during spreading depression and global cerebral ischemia of rats

Tissue levels of inorganic phosphate (iP-) and lactate (lac) increase during cerebral ischemia and cortical spreading depression (SD). Since cell membranes become leaky during these insults, iP- and lac were expected to leak into the extracellular space (ECS). In order to find out whether this occurs or does not, a microdialysis (MD) fiber was implanted into the cortex of anesthetized rats and extracellular lactate (lac(e)) and extracellular iP- (iPe-) were determined during various insults. Extracellular lactate increased to about the same extent during ischemia and SD. In contrast, iPe- increased during ischemia but not during SD. Instead, iPe- started to rise after SD and reached its maximum about 45 min later. The distinct pattern of iPe- in comparison to lac(e) during the above mentioned insults points to a qualitative difference of the underlying mechanisms: whereas lac appears within the ECS at any stressful situation, elevation of iP- within the ECS indicates depletion of energy stores in parallel to the lack of control of ion homeostasis.

Decrease of free calcium concentration at the outer surface of identified snail neurons during paroxysmal depolarization shifts

Changes of free calcium concentration at the outer neuronal surface during paroxysmal depolarization shifts elicited by pentylenetetrazol were measured. Investigations were performed on the identified neuron B3 of the buccal ganglion of Helix pomatia. Extracellular calcium concentration was recorded by calcium-selective microelectrodes. The extracellular calcium concentration steeply decreased with the commencement of paroxysmal depolarization and started to reincrease when the paroxysmal depolarization had reached its plateau level. It is concluded that an influx of calcium ions takes place during paroxysmal depolarization shifts.

Continuous measurement of pentylenetetrazol concentration by a liquid ion exchanger microelectrode

A double-barrelled microelectrode is described, which permits the continuous measurement of the concentration of the epileptogenic agent pentylenetetrazol (PTZ). The electrode is based on the liquid potassium exchanger (Corning No. 477 317) and enables measurements of PTZ concentration in physiological salines down to 1 mM. The electromotive behaviour of the liquid membrane against PTZ cannot directly be described by the Nicolsky-Eisenman formalism. It is suggested that specific interactions of the PTZ molecule with the Corning ligand are involved in the potential generating mechanisms.

Neurons, Glia and Ions in Hypoxia, Hypercapnia and Acidosis

Effects of hypoxia, hypercapnia and/or acidosis on membrane properties were investigated in cortical neurons, glial cells and spinal neurons in-vivo as well as in pyramidal cells of hippocampal slice preparations and in cultured sensory spinal ganglion (SSG) cells in-vitro.