Existence of different populations of unitary evoked postsynaptic potentials at the frog neuromuscular junction]

The postsynaptic response to monoquantic evoked transmitter release (mean quantal content about 0.3) has been studied at temperatures from 10 to 23 degrees C. The delay between nerve stimulation (1 to 10 Hz) and the unitary postsynaptic potentials fluctuates by steps. The existence of preferential delay sites can always be detected (mean number 13.5 +/- 3.1). Identical delay unitary postsynaptic potentials often shows identical amplitude and identical time to peak. These results suggest that few emitting sites are preferentially activated along the nerve terminal at low level release during long lasting stimulation. The "single process" assumption used in statistical studies of transmitter release is probably oversimplified.     

Periodic variations in motor endplate potentials]

The amplitudes of motor end-plate potentials in the Frog have been measured during repetitive stimulations of the motor nerve at frequencies between 0,5 and 30 Hz. A serial analysis showed that cyclic variations of these amplitudes were superimposed on the random fluctuation of epp due to the quantal nature of transmitter release. The period of these cyclic variations varied between 3 and 10 stimulations. This period was not significantly related to the frequency of the stimulation. The frequency spectrum analysis of the epp amplitudes showed similar values for the period of the cyclic variation of epp. The same kind of analysis applied to a binomial series of random numbers did not significantly present periodic fluctuations. The same analysis was applied to mean amplitudes of groups of 5 to 120 successive epps at the same end-plate. Periodic fluctuations were identified with periods of about 10 to 180 sec. It is suggested that periodic failures of nerve spike propagation in nerve terminals at sites of low safety factor, as at branchings, are responsible for the observed cyclic variation of epp.     

Reticular potentials evoked by electrical stimulation of individual semicircular canals.

Responses of pontine reticular formation neurons following single shock electrical stimulation of single semicircular canals were recorded with tungsten microelectrodes in 40 curarized guinea-pigs. The field and unitary potentials obtained from 62 reticular sites, exhibited latency values ranging from 0.3 to 2.5 msec. The early latencies (0.3-0.5 msec) have been interpreted as responses mediated by primary vestibular fibres projecting directly to the reticular substance.     

Reticular potentials evoked by electrical stimulation of individual semicircular canals

Summary Responses of pontine reticular formation neurons following single shock electrical stimulation of single semicircular canals were recorded with tungsten microelectrodes in 40 curarized guinea-pigs. The field and unitary potentials obtained from 62 reticular sites, exhibited latency values ranging from 0.3 to 2.5 msec. The early latencies (0.3–0.5 msec) have been interpreted as responses mediated by primary vestibular fibres projecting directly to the reticular substance.This work was supported by a grant of CNR.     

Medial forebrain bundle projections to the nucleus of the diagonal band of Broca.

The electrophysiological characteristics of the medical forebrain bundle (MFB) projections to the nucleus of the diagonal band of Broca (nDBB) were studied in acutely prepared cats. MFB stimulation evoked field potentials which consisted of a large negative wave followed by a shallow positivity. Extracellular unitary discharges appeared out of the negativity. In addition, intracellularly recorded EPSPs showed no significant shift in the latency to onset with changes in stimulus intensity. These observations indicate that at least some of the MFB projections to the nDBB are excitatory with respect to their target cells.     

Oscillatory after-potentials and triggered-automaticity in mammalian ventricular muscle fibres at high resting potentials.

Oscillatory after-potentials and triggered-automaticity were observed in dog ventricular muscle fibres when the fibres were exposed to K+-free,high-Ca++-solutions after K+-free,Ca++-free perfusion. They appeared at membrane potentials more negative than--60 m V.     

Purification of rat brain guanylate cyclase]

The purification of guanylate cyclase has been achieved. After electrophoresis on polyacrylamide gel only one protein band was observed. The low factor of purification must therefore be ascribed to the loss of an activator of guanylate cyclase. Stimulation of the activity by nitroprusside is also lost during purification. The purified enzyme follows Michaelis--Menten kinetics, it is activated by Mn++ ions and inhibited by triphospho nucleotides.     

Origin of the differences of superficial potentials in Rana esculenta]

The spatial distributions of superficial D.C. potentials on the skin of Rana esculenta have been compared to those of the intensity of short-circuit current (S.C.C.) expressing the transcutaneous active transport of sodium ions. It has been observed that the sites of maximum D.C. potentials coincide with the localisations of maximum S.C.C. values. Moreover, superficial D.C. potentials and S.C.C. are similarly modified by the depression of metabolic activity due to lowered temperature or poisoning by dinitrophenol (DNP). It is thus proposed that the spatial distribution of the transcutaneous active transport system for sodium ions is the origin of the electric generator of superficial D.C. potentials.     

Activity increases quantal size at the frog neuromuscular junction

Two h of nerve stimulation at 10 Hz or of elevated spontaneous release in hypertonic solution increased the size of miniature end-plate potentials (m.e.p.p.'s) and currents at the frog neuromuscular junction, probably by increasing the amount of acetylcholine in a quantum. Increases in quantal size may modulate synaptic transmission.     

Variation of the time constant (tau) of the decay of end-plate current during focalized transmitter release]

The variations of the time constant tau of the end-plate current (epc) have been studied at the clamped neuromuscular junction of the frog while transmitter release was focalised by local iontophoretic application of Ca++. In the absence of any anticholinesterasic drug, tau varies according to the variations of the intensity of epc (Iepc) due to pre or postsynaptic experimental procedure. It is suggested that focalisation of transmitter release induces local acetylcholinesterase inhibition by an excess of substrate; then the transmitter life time in the synaptic cleft is momentarily increased, allowing repeated binding of Ach to postsynaptic receptors.     

Characterization of the (Na+-K+)-ATPase from endometrial plasma membranes of immature mammals]

The (Na+-K+)-ATPase in plasma membrane from Mammiferous endometrium is characterized by the Mg/ATP ratio equal to one, and by a distinct affinity for Na+ (1.3 mM) and K+ (2 mM). The activity is maximum for pH 7.4-7.5 in presence of Mg++ 2mM and ATP 2 mM, Na+ 140 mM and K+ 10 mM.     

Manganese action potentials in mammalian cardiac muscle.

The membrane potential in guinea-pig's papillary muscles from right ventricle was recorded by glass microelectrodes and stimulation was effected by current pulses applied through a sucrose-gap. Action potentials with overshoot were recorded in the solution lacking Na+ and Ca++ but containing 2-95 mM Mn++. The overshoot was increased with the increase of [Mn++]o by about 30 mV/decade. Similar Mn++ dependent action potentials were also obtained in Na-free solution containing 0.6 mM Ca++. The results indicate that Mn inward current is sufficient to generate action potentials in cardiac muscle.     

Changes in transmitter release at frog neuromuscular junction induced by 4-aminopyridine]

4-aminopyridine (4-AP) at micromolar concentrations, increases the end-plate potential amplitude in curarized preparations and the mean quantal content in every preparation tested, but the spontaneous release is not modified by 4-AP. These results can explain the anticurare activity observed in the wole animal or in vitro. 4-AP prolongs the falling phase of the muscle action potential without change in the muscle membrane potential.     

Influence of ethanol on calcium, inositol phospholipids and intracellular signalling mechanisms

Studies have implicated Ca++ in the actions of ethanol at many biochemical levels. Calcium as a major intracellular messenger in the central nervous system is involved in many processes, including protein phosphorylation enzyme activation and secretion of hormones and neurotransmitters. The control of intracellular calcium, therefore, represents a major step by which neuronal cells regulate their activities. The present review focuses on three primary areas which influence intracellular calcium levels; voltage-dependent Ca++ channels, receptor-mediated inositol phospholipid hydrolysis, and Ca++/Mg++-ATPase, the high affinity membrane Ca++ pump. Current research suggests that a subtype of the voltage-dependent Ca++ channel, the dihydropyridine-sensitive Ca++ channel, is uniquely sensitive to acute and chronic ethanol treatment. Acute exposure inhibits, while chronic ethanol exposure increases 45Ca++-influx and [3H]dihydropyridine receptor binding sites. In addition, acute and chronic exposure to ethanol inhibits, then increases Ca++/Mg++-ATPase activity in neuronal membranes. Changes in Ca++ channel and Ca++/Mg++-ATPase activity following chronic ethanol may occur as an adaptation process to increase Ca++ availability for intracellular processes. Since receptor-dependent inositol phospholipid hydrolysis is enhanced after chronic ethanol treatment, subsequent activation of protein kinase-C may also be involved in the adaptation process and may indicate increased coupling for receptor-dependent changes in Ca++/Mg++-ATPase activity. The increased sensitivity of three Ca++-dependent processes suggest that adaptation to chronic ethanol exposure may involve coupling of one or more of these processes to receptor-mediated events.     

Accelerated synaptic transmission in nucleus ventralis-postero-lateralis during deep sleep

Conclusion It is clear that during deep sleep the response evoked in the somatosensory cortex of the cat by shocks to the cutaneous nerve or medial lemniscus is not only higher² but has a shorter latency as well. Our experiments demonstrate that this decrease in latency occurs during transmission through the nucleus VPL. No change in synaptic transmission time was observed in nuclei gracilis and cuneatus or in the cortex itself.

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Riassunto La latenza delle risposte evocate nella corteccia somatica sia da stimolazione cutanea che del lemnisco mediale diminuisce significativamente con 1'aumentare della profondità del sonno. Tale fenomeno è dovuto ad una accelerata trasmissione degli impulsi ascendenti a livello del nucleo ventro-postero-laterale del talamo.

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Parts of these results have been presented at a meeting of the Società italiana di Biologia sperimentale, held in Genoa on February 12, 1965.     

Judgemental revision of sales forecasts: A longitudinal eetension

When quantitative models are used for short-term multi-item sales forecasts it is possible that the managers who use such forecasts may disagree with at least some of the estimates obtained, and wish to change them so that they become more consistent with their own (subjective) evaluation of the marketplace. This study reports on an analysis of the effectiveness of judgemental revision of sales forecasts over six quarterly forecasting periods. The results give general support for the practice of forecast manipulation as a means of improving forecasting accuracy. It is also observed that the effectiveness of revision activity varies across different time periods.     

Un curare d'une Erythrine africaine

Summary An alcaloid C₁₆H₁₉NO₃ has been isolated fromErythrina tholloniana; the iodohydrate of this erythroidine has a melting point of 225°C and 239°C for its chlorhydrate. It has a powerful curare-like action on the frog or on its isolated sciatic-sartorius preparation; at a concentration of less than 1/1,000,000, a complete neuromuscular block is produced: the electrical stimulation of the motor nerve does not produce any contraction, but the muscle reacts by an end-plate potential having the same characteristics (shape, duration, possibility of summation) as the electrical waves produced in the same preparation curarized by ordinary curare or by quaternary ammonium derivatives. Decurarization by veratrine 1/200,000 is accompanied by the same electrical reactions as those which have been described in preparations treated by curare.On mammals, the alcaloid has little curariform activity; on the isolated phrenic-diaphragm preparation of the rat, incomplete block was produced at a concentration of 1/5000.     

Possible role of intestinal alkaline phosphatase activity in thiamine transport.

Thiamine deficiency caused a marked decrease of intestinal alkaline phosphatase (al-Pase) activity, but had no effect on the Ca++-ATPase activity and Ca++-absorption in rats. The al-Pase activity was significantly decreased 1 h after oral administration of ethanol at 0.5 and 2.5 g/kg. In contrast, Mg++-, Ca++-and (Na+ + K+)-ATPase activities did not change after the administration of ethanol. These findings show that the al-Pase activity, unlike the Ca++-ATPase activity, is not related to Ca++-absorption. A possible role of al-Pase activity in the active transport of thiamine in the intestine was discussed.     

Activity increases quantal size at the frog neuromuscular junction

Summary Two h of nerve stimulation at 10 Hz or of elevated spontaneous release in hypertonic solution increased the size of miniature end-plate potentials (m.e.p.p.'s) and currents at the frog neuromuscular junction, probably by increasing the amount of acetylcholine in a quantum. Increases in quantal size may modulate synaptic transmission.Acknowledgments. Supported by grant 10320 from the NINCDS and by a grant from the MDA. We are grateful to Dr I.S. Cohen for participating in some of the experiments and for helpful criticism, and to Drs C. Clausen and G. Baldo for help with the computer. Some of the results were presented at a meeting of the Physiological Society.     

Zinc antagonizes the effect of botulinum type A toxin at the mouse neuromuscular junction

Zn2+ (10-100 microM) elevated the frequency of miniature end-plate potentials (MEPPs) in the mouse diaphragm. The effect did not depend on external Ca2+. Botulinum type A toxin (BTXA, 50 ng/ml) abolished MEPPs almost completely within 30 min. Zn2+ (100 microM) restored MEPPs and increased their frequency after they had been abolished by BTXA in Ca2+ -free solutions. The antagonistic effect of Zn2+ in the Ca2+ -free solution was reduced by exposing the diaphragm to the toxin in the Ca2+ -free solutions containing high K+. Thus, the action of BTXA is probably enhanced by depolarization of the motor nerve terminals.