Effects of Lateral Inhibition on Fluctuations of the Impulse Rate

Inhibition from neighboring eccentric cells has an effect on the variability of firing of a given eccentric cell. The reduction in the average impulse rate which is caused by inhibition decreases the variance of the impulse rate. However, this reduction of the average rate increases the coefficient of variation of the impulse rate. Inhibitory synaptic noise should add to the low frequency portion of the variance spectrum of the impulse rate. This occurs because of the slow time course of inhibitory synaptic potentials. As a consequence, inhibition decreases the signal-to-noise ratio for low frequency modulated stimuli.     

Effect of small doses of roentgen radiation on the spontaneous impulse activity of the hippocampus in vitro

X-Irradiation of rat hippocampus in vitro with low doses accelerated spontaneous impulse passage without concomitant changes in synaptic activity. There was a negative correlation between the original frequency of neuron discharges and the degree of quickening the impulses in response to the effect of radiation. Perfusion of slices by a noncalcium solution blocked the synaptic transmission but did not influence the response to the effect of ionizing radiation.     

Synaptic diversity and differentiation: Crustacean neuromuscular junctions

Crustacean motor neurons exhibit a wide range of synaptic responses. Tonically active neurons generally produce small excitatory postsynaptic potentials (EPSPs) at low impulse frequencies, and are able to release much more transmitter as the impulse frequency increases. Phasic neurons typically generate large EPSPs in their target cells, but have less capability for frequency facilitation, and undergo synaptic depression during maintained activity. These differences depend in part upon the neuron's ongoing levels of activity; phasic neurons acquire physiological and morphological features of tonic neurons when their activity level is altered. Molecules responsible for adaptation to activity can be sought in single identified phasic neurons with current techniques. The fact that both phasic and tonic neurons innervate the same target muscle fibers is evidence for presynaptic determination of synaptic properties, but there is also evidence for postsynaptic determination of specific properties of different endings of a single neuron. The occurrence of high- and low-output endings of the same tonic motor neurons on different muscle fibers suggests a target-specific influence on synaptic properties. Structural variation of synapses on individual terminal varicosities leads to the hypothesis that individual synapses have different probabilities for release of transmitter. We hypothesize that structurally complex synapses have a higher probability for release than the less complex synapses. This provides an explanation for the larger quantal contents of high-output terminals (where the proportion of complex synapses is higher), and also a mechanism for progressive recruitment of synapses during frequency facilitation.     

Repetitive impulse activity potentiates spontaneous acetylcholine secretion at developing neuromuscular synapses.

The effects of presynaptic impulse activity on the transmitter secretion at developing neuromuscular junctions were examined in Xenopus nerve-muscle cultures. Repetitive suprathreshold stimulation of the presynaptic neuron results in marked potentiation of spontaneous synaptic activity, as shown by whole-cell voltage-clamp recording of synaptic currents in the postsynaptic muscle cell. Our results are consistent with the notion that synaptic efficacy of the developing synapse is potentiated by the presence of electrical activity. Such activity-dependent synaptic modulation enables the early neuronal activity to play a regulatory role during the maturation of synaptic connections.     

AN ELECTRON MICROSCOPIC STUDY OF THE DEVELOPMENT OF SYNAPSES IN CULTURED FETAL MOUSE CEREBRUM CONTINUOUSLY EXPOSED TO XYLOCAINE

Explants of fetal mouse cerebral cortex, continuously exposed to the local anesthetic Xylocaine from the time of explantation to the time of fixation, were examined in the electron microscope to determine whether morphologically normal synapses and potentially functional interneuronal synaptic networks can form in the absence of electrical impulse activity. Morphological differentiation of complex synaptic networks proceeds normally, and the drug does not alter the fine structure of the formed synapses. These observations are consonant with the electrophysiological data which show that the potential for complex bioelectric activity can develop in the absence of its expression. The development and maturation of functional synaptic networks, then, is not contingent upon prior electrical impulse activity. These data support the concept that organized neuronal assemblies are formed in forward reference to their ultimate function.     

The effect of substance P on the neuronal activity of the antinociceptive system

The experiments on rats showed that the 1 micrograms substance P injection to dorsal raphe nucleus caused prolonged (24 hours of study) analgetic effect--it enhances the reaction latent period to thermal nociceptive stimulation, intensifies the background impulse activity, rises the middle frequency of neuron discharges and creates high-frequency neurons as well as the neurons with burst impulse activity. The supposition is being confirmed that the mechanism of antinociceptive structures activation leads to analgesia caused by substance P.     

Comparative analysis of the effect of endogenous antibiotic defensin NP-1 and aminoglycoside antibiotic gentamicin on synaptic transmission in receptors of the frog vestibular apparatus

The effect of human and rabbit neutrophilic defensins NP-1 and amonoglycoside antibiotic gentamicin on the synaptic transmission in the afferent synapse of isolated vestibular apparatus of the frog has been comparatively studied. Both defensins proved active in the concentration range of 0.0001 to 1 nM and efficiently decreased the impulse frequency in the afferent nerve fibers in a concentration-dependent manner. No significant differences in the efficiency of rabbit and human defensin NP-1 have been revealed in these experiments. Gentamicin also had an inhibitory effect on the afferent discharge in the concentration range of 10–500 μM (0.5–25 mg/kg). The inhibitory effect of gentamicin on the impulse activity of the vestibular nerve was observed at therapeutic doses. The excitatory effect of the putative neurotransmitter L-glutamate was considerably inhibited by defensin NP-1. These findings suggest that the mechanism of defensin action involves a modification of the synaptic transmission in the hair cell receptor and modulation of the effect of L-glutamate.     

Signal transformation with pairing of sensory stimuli

Rotation of the isolated nervous system of Hermissenda in a caudal orientation causes a synaptic hyperpolarization accompanied by elimination of impulse activity during the steady-state phase of type A but not type B photoreceptors' responses to light. Rotation of the isolated nervous system in a cephalic orientation causes a synaptic depolarization with increase of impulse activity during the steady-state phase of both type A and type B photoreceptors' responses to light. These effects of rotation on photorecptors are explained by known synaptic interactions. Sufficient redundancy is found to be provided by the neural organization of the visual system and its interaction with the statocyst to preserve much of the visual information in spite of signal transformation in specific photorecptors resulting from pairing of rotation with light.     

Development of synaptic transmission at autonomic synapses in vitro revealed by cytochrome oxidase histochemistry

We have studied the development of synaptic transmission by innervating sympathetic neurons in vitro and monitoring synaptic activity with both physiological recording and cytochrome oxidase histochemistry. The onset of synaptic transmission was reflected in increased cytochrome oxidase reaction product within individual neurons. Within 24 hours of co-culture, relatively low frequency suprathreshold potentials were recorded in approximately 20% of the innervated neurons. At this stage the cytochrome oxidase activity of innervated neurons, as assessed by optical density of the histochemical reaction product, was increased twofold compared with uninnervated neurons. Over the next 2-4 days of innervation, changes in the pattern and extent of synaptic activity and superthreshold events were accompanied by a net fourfold increase in cytochrome oxidase activity levels compared with noninnervated neurons. The increase in density of cytochrome oxidase reaction product observed after innervation was reversed completely by blockade of synaptic transmission. Differences in the efficacy of synaptic input provided to the sympathetic neurons by appropriate versus inappropriate presynaptic sources was determined by co-culturing sympathetic neurons with explants that contained either preganglionic neurons or somatic motor neurons. Although sympathetic neurons innervated by motor neuron explants had increased levels of cytochrome oxidase activity compared with noninnervated controls, the density of cytochrome oxidase reaction product was even greater in sympathetic neurons innervated by preganglionic explants. We conclude that both the onset of innervation of sympathetic neurons as well as the subsequent maturation of synaptic function is directly reflected in graded increases in cytochrome oxidase reaction product.     

Interaction between the Dopaminergic and GABA-ergic Systems of the Cortex during Conditioning

Impulse activities were recorded from neurons of the sensorimotor cortex of cats, trained to perform a conditioned placing reaction, before, during, and after iontophoretic application of the synaptically active drugs dopamine (DA) and GABA. Our experiments demonstrated that in most cases isolated application of DA increased the frequency of the impulse activity and the number of spikes related to the placing reaction. On the other hand, GABA evoked decreases in both indexes characterizing the impulse activity. In the case of co-application of DA with GABA, we observed both increases and decreases in the background firing rate activity and in the number of spikes related to the placing reaction. Our results suggest that interaction between the DA-ergic and GABA-ergic systems is realized at the receptor level and cannot be interpreted in an oversimplified manner.     

Methodological problems in the histochemical demonstration of succinate semialdehyde dehydrogenase activity

Methodological aspects of the histochemical technique for the demonstration of succinate semialdehyde dehydrogenase activity (EC 1.2.1.24) (indicative of the degradative step of gamma-aminobutyric acid catabolism) have been analysed in rat Purkinje neurons, where gamma-aminobutyric acid has been shown to be a neurotransmitter, and in hepatocytes, where it is metabolized. During a histochemical incubation for the enzyme, artefacts of succinate dehydrogenase activity and the 'nothing dehydrogenase' reaction are produced. Inhibition of these artefacts by the addition of two inhibitors, malonate and p-hydroxybenzaldehyde, revealed specific reaction products. Formazan granules, which can be ascribed only to specific succinate semialdehyde dehydrogenase activity, are obtained by adding malonate to the incubation medium in order to inhibit both succinate dehydrogenase activity and nothing dehydrogenase. The formation of these granules is completely inhibited by p-hydroxybenzaldehyde, an inhibitor of succinate semialdehyde dehydrogenase activity. Different levels of succinate semialdehyde dehydrogenase activity were noted in Purkinje neurons. This activity was also found in hepatocytes, mostly in the portal area, but with a lesser degree of intensity and specificity. Indeed, non-specific formazan granules were still produced, because of the 'nothing dehydrogenase' reaction, even in the presence of malonate. Thus, a malonate-insensitive 'nothing dehydrogenase' reaction seems to be present in neural and hepatic tissues.     

The photo-oxidation of succinate by chromatophores of Rhodospirillum rubrum

1. The stoicheiometry of the photo-oxidation of succinate by chromatophores has been investigated with [2,3-¹⁴C₂]succinate. It was found that there is a stoicheiometric relationship between the amount of succinate oxidized and the NAD reduced, and that fumarate is the only product of succinate oxidation. 2. The possibility of a direct hydrogen transfer from succinate to NAD in this reaction was investigated with tritiated substrates. With tritiated succinate less than 3% of the activity expected if direct hydrogen transfer occurred was recovered in the NADH₂, and this was due to contamination with the substrate. In experiments with tritiated water, NADH₂ was labelled, and had half the specific activity of the water, as expected if water was the source of protons. It was also found that chromatophores catalyse an exchange reaction between NADH₂ and water. 3. It is concluded that the exchange reaction makes it impossible to interpret these results as indicating either a hydrogen-transfer or an electron-transfer mechanism for the photoreduction reaction.     

The background and evoked neuronal impulse activity of embryonic neurotransplant of somatosensory brain cortex in rats

The investigation was intended for studying the character of the background and evoked impulse activity of embryonic neurotransplant neurons 4 months after homotopical allotransplantation into the barrel field of somatosensory recipient's brain cortex of the rat. It is established, that the current average frequency of background impulse activity of transplant neurons is reduced in comparison with one of the control rats. It is shown that the evoked impulse activity of neurotransplant develops with the long latency than in somatosensory cortex of the control animals. Thus in patterns of the evoked activity of neurotransplant cells reactions, characteristic for the neurons of barrel field somatosensory recipient's cortex of control rats are registered: an increase of frequency of pulses' generating, or alternating of the activation and reduction periods of impulse frequency with its subsequent regeneration up to a pristine level.     

Effect of reduced impulse activity on the development of identified motor terminals in Drosophila larvae

In Drosophila larvae, motoneurons show distinctive differences in the size of their synaptic boutons; that is, axon 1 has type Ib ("big" boutons) terminals and axon 2 has type Is ("small" boutons) terminals on muscle fibers 6 and 7. To determine whether axon 1 develops large boutons due to its high impulse activity, we reduced impulse activity and examined the motor terminals formed by axon 1. The number of functional Na(+) channels was reduced either with the nap(ts) mutation or by adding tetrodotoxin (TTX) to the media (0.1 microg/g). In both cases, the rate of locomotion was decreased by approximately 40%, presumably reflecting a decrease in impulse activity. Locomotor activity was restored to above wild-type (Canton-S) levels when nap(ts) was combined with a duplication of para, the Na(+)-channel gene. Lucifer yellow was injected into the axon 1 motor terminals, and we measured motor terminal area, length, the number of branches, and the number and width of synaptic boutons. Although all parameters were smaller in nap(ts) and TTX-treated larvae compared to wild-type, most of these differences were not significant when the differences in muscle fiber size were factored out. Only bouton width was significantly smaller in both different nap(ts) and TTX-treated larvae: boutons were about 20% smaller in nap(ts) and TTX-treated larvae, and 20% larger in nap(ts); Dp para(+) compared to wild-type. In addition, terminal area was significantly smaller in nap(ts) compared to wild-type. Bouton size at Ib terminals with reduced impulse activity was similar to that normally seen at Is terminals. Thus, differences in impulse activity play a major role in the differentiation of bouton size at Drosophila motor terminals.     

Toward an integrated continuum model of cerebral dynamics: the cerebral rhythms, synchronous oscillation and cortical stability

Continuum models of cerebral cortex with parameters derived from physiological data, provide explanations of the cerebral rhythms, synchronous oscillation, and autonomous cortical activity in the gamma frequency range, and suggest possible mechanisms for dynamic self-organization in the brain. Dispersion relations and derivations of power spectral response for the models, show that a low frequency resonant mode and associated travelling wave solutions of the models' equations of state can account for the predominant 1/f spectral content of the electroencephalogram (EEG). Large scale activity in the alpha, beta, and gamma bands, is accounted for by thalamocortical interaction, under regulation by diffuse cortical excitation. System impulse responses can be used to model Event-Related Potentials. Further classes of local resonance may be generated by rapid negative feedbacks at active synapses. Activity in the gamma band around 40 Hz, associated with large amplitude oscillations of pulse density, appears at higher levels of cortical activation, and is unstable unless compensated by synaptic feedbacks. Control of cortical stability by synaptic feedbacks offers a partial account of the regulation of autonomous activity within the cortex. Synchronous oscillation occurs between concurrently excited cortical sites, and can be explained by analysis of wave motion radiating from each of the co-active sites. These models are suitable for the introduction of learning rules-most notably the coherent infomax rule.     

Role of microstructure of nerve impulse train in relation to transmission of neuronal activity and coding mechanism of neural information

Input-output relation were of giant neurons of a marine mollusc, Onchidium verruculatum, and a computer-simulated neuron investigated in terms of microstructure of nerve impulse train. The microstructure of input impulse train, the size of a unitary EPSP, and the extent of spontaneous firing activity of a single neuron had an important influence upon the effective summation of arriving synaptic inputs, the elicitation of output spikes, and intervals between succeeding output spikes. The neuron responded differently to respective input trains with different time structures, i.e. it discriminated input time pattern to various degrees. The manner in discrimination of input time pattern was dependent on the size of the unitary EPSP and the extent of the spontaneous firing activity, if it had. Some discussions were made with regard to possible coding systems of neural signal, assuming a frequency code and/or a pattern code.     

Analysis of the regulation of noradrenaline secretion by autoadrenoreceptors and stimulation frequency

A mathematical model is presented which quantitatively describes the value of secreted mediator to each subsequent impulse in the series of presynaptic impulses. The model is constructed with the account taken of the role of presynaptic adrenoreceptors regulating noradrenaline secretion. An analysis of the model shows that the observed decrease and further stabilization of presynaptic responses in the series of presynaptic impulses observed in neurophysiological experiments can be connected with the work of alpha- and beta-autoadrenoreceptors. The increase of impulsation frequency affects the sensitivity of these receptors, which brings about an increase of concentration of secreted to each subsequent impulse mediator in the synaptic slit in the series of presynaptic impulses and stabilization of secretion at a higher level.