Neuronal spike trains and stochastic point processes. I. The single spike train

In a growing class of neurophysiological experiments, the train of impulses (“spikes”) produced by a nerve cell is subjected to statistical treatment involving the time intervals between spikes. The statistical techniques available for the analysis of single spike trains are described and related to the underlying mathematical theory, that of stochastic point processes, i.e., of stochastic processes whose realizations may be described as series of point events occurring in time, separated by random intervals. For single stationary spike trains, several orders of complexity of statistical treatment are described; the major distinction is that between statistical measures that depend in an essential way on the serial order of interspike intervals and those that are order-independent. The interrelations among the several types of calculations are shown, and an attempt is made to ameliorate the current nomenclatural confusion in this field. Applications, interpretations, and potential difficulties of the statistical techniques are discussed, with special reference to types of spike trains encountered experimentally. Next, the related types of analysis are described for experiments which involve repeated presentations of a brief, isolated stimulus. Finally, the effects of nonstationarity, e.g. long-term changes in firing rate, on the various statistical measures are discussed. Several commonly observed patterns of spike activity are shown to be differentially sensitive to such changes. A companion paper covers the analysis of simultaneously observed spike trains.     

Physiological Control of Molluscan Gill Cilia by 5-Hydroxytryptamine

An examination is made of the hypothesis that endogenous 5-hydroxytryptamine (5-HT) serves as a local hormone regulating ciliary activity in the lamellibranch gill. These cilia are sensitive to exogenous 5-HT and respond to it by a prompt, sustained, and reversible rise in beat frequency; at the same time the carbohydrate metabolism is stimulated, as described elsewhere. Control gill contains small but definite amounts of endogenous 5-HT according to bioassay, fluorometry, and chromatography. The amount can be increased markedly by exposing the isolated gill to the precursor substance 5-hydroxytryptophan but not l-tryptophan. As the tissue level of 5-HT rises, the spontaneous beat frequency also rises. Both remain elevated for hours and perhaps for days. The gill of Mytilus edulis is richer than the gill of Modiolus demissus in both endogenous 5-HT and effective 5-hydroxytryptophan decarboxylase activity. Modiolus gill lacks the 5-hydroxyindole oxidase by which Mytilus gill destroys 5-HT. What if any mechanism exists in Modiolus for degrading 5-HT is not known, but monoamine oxidase is not present. The 5-HT content of Mytilus and Modiolus gill cannot be modified by treatment with reserpine or α-methyl-dopa. Which cells of the gill synthesize and destroy 5-HT has not been established, but these observations support the concept that the physiological activity of lamellibranch gill cilia is controlled by a serotonergic mechanism.     

POLYCYTHEMIA VERA—Peripheral Vascular Manifestations

The presenting manifestations of polycythemia vera are often complications involving the vascular system. These include myocardial infarction, cerebro-vascular accidents and ischemic changes in the extremities.The concept of increased atherogenesis in cases of polycythemia vera has been questioned. A possible mechanism by which small, otherwise subclinical atheromatous plaques produce ischemic symptoms in patients with polycythemia vera is discussed. The blood in polycythemic patients has been shown to have an increased viscosity resulting in a prolonged circulation time. If a small atheromatous plaque is present in association with increased blood viscosity, this combination may well produce ischemic symptoms. This explains why treatment of polycythemia vera, with restoration of blood to normal viscosity, often reverses the patient''s ischemic symptoms.Two cases of polycythemia vera here reported, in which the presenting manifestations were gangrenous extremities, emphasize the need for prompt diagnosis and treatment of polycythemia vera. In the first case, early recognition and treatment of polycythemia vera successfully reversed the ischemic changes in the extremities, while failure of early recognition and treatment in the second case resulted in two major amputations.     

Effect of Ethanol on the Sodium and Potassium Conductances of the Squid Axon Membrane

The effects of ethanol on squid giant axons were studied by means of the sucrose-gap technique. The membrane action potential height is moderately reduced and the duration sometimes shortened by ethanol in sea water. Voltage clamp experiments showed that ethanol in sea water reduced the maximum membrane conductances for sodium (g'_Na) and potassium (g'_K). In experiments with multiple application of ethyl alcohol to the same spot of membrane, a reduction of g'_Na to 82 per cent and of g'_K to 80 per cent of their value in sea water was brought about by 3 per cent ethanol (by volume) while 6 per cent caused a decrease of g'_Na to 59 per cent and of g'_K to 69 per cent. Ethanol has no significant effect on the steady-state inactivation of g_Na (as a function of conditioning membrane potential) or on such kinetic parameters as τ_h or the time course of turning on gi g_Na and g_K. It is concluded that ethanol mainly reduces g_Na and g_K in the Hodgkin-Huxley terminology.     

Biosynthesis of (-)-Kaurene in Cell-free Extracts of Immature Pea Seeds

Mevalonate-¹⁴C was incorporated into (—)-kaurene-¹⁴C in cell-free extracts of immature pea (Pisum sativum L.) seeds. The identification of ¹⁴C-product as (—)-kaurene was based on: A) comparison with authentic (—)-kaurene on thin-layer and gas-liquid chromatography; and B) oxidation of ¹⁴C-product and (—)-kaurene with osmium tetroxide to form the common derivative kaurane-16,17-diol. The enzyme system is heat labile and is dependent upon ATP and Mg²⁺ or Mn^2-, with Mn²⁺ being a more effective activator than Mg²⁺. The reaction rate was proportional to enzyme concentration in reaction mixtures containing 0.45 to 1.8 mg protein n/ml, and was linear with time through 120 minutes in standard reaction mixtures. Enzyme preparations from immature seeds of tall and dwarf peas appeared to synthesize (—)-kaurene at the same rate. Synthesis of (—)-kaurene was readily inhibited by Amo-1618. (2-Chloroethyl)-trimethylammonium chloride (CCC) also inhibited (—)-kaurene synthesis; however, approximately 1000-fold higher concentrations of CCC were required to evoke the same percentages of inhibition as Amo-1618.     

THALASSIOMYCETES II. NEW GENERA AND SPECIES OF DEUTEROMYCETES

Meyers , Samuel P. (U. Miami, Coral Gables, Fla.) and Royall T. Moore . Thalassiomycetes II. New genera and species of Deuteromycetes. Amer. Jour. Bot. 47(5) : 345-349. Illus. 1960.–On the basis of taxonomic studies, 3 new monotypic thalassic genera are erected. These are: Cirrenalia, type C. macrocephala (=Helicoma macrocephala Kohlmeyer) ; Cremasteria, type C. cymatilis; Culcitalna, type C. achraspora . Also described is a new species of Humicola, H. alopallonella, which constitutes the first report of this genus from the marine environment.     

Ionic Current Measurements in the Squid Giant Axon Membrane

The concepts, experiments, and interpretations of ionic current measurements after a step change of the squid axon membrane potential require the potential to be constant for the duration and the membrane area measured. An experimental approach to this ideal has been developed. Electrometer, operational, and control amplifiers produce the step potential between internal micropipette and external potential electrodes within 40 microseconds and a few millivolts. With an internal current electrode effective resistance of 2 ohm cm.², the membrane potential and current may be constant within a few millivolts and 10 per cent out to near the electrode ends. The maximum membrane current patterns of the best axons are several times larger but of the type described by Cole and analyzed by Hodgkin and Huxley when the change of potential is adequately controlled. The occasional obvious distortions are attributed to the marginal adequacy of potential control to be expected from the characteristics of the current electrodes and the axon. Improvements are expected only to increase stability and accuracy. No reason has been found either to question the qualitative characteristics of the early measurements or to so discredit the analyses made of them.