A computer program for simulating a network of interacting neurons. II. Programming aspects.
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Biomedical subjects
Publications and source records attributed to D H Perkel.
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Recent studies of the mechanism of quantal neurotransmitter release have assumed that the number of quanta released at each stimulation is binomially distributed and have sought to estimate the binomial parameters n and p. Mathematical analysis and computer simulations show that temporal variation in the number of eligible or filled release sites and either spatial or temporal variation in the probability of release at a site can drastically bias such estimates, while the experimental histograms remain statistically indistinguishable from those predicted by the binomial law. Interpretation of the estimates n and p in terms of ultrastructural or physiological characteristics of the nerve terminal is liable to significant error if departures from the binomial assumptions are not suitably assessed.
A scatter diagram is described that displays the relative timings of nerve impulses in 3 simultaneously monitored neurons. The technique is a generalization of the cross-correlation histogram for two impulse trains. The time intervals between impulses in different neurons are plotted on triangular coordinates to yield a Joint Impulse Configuration Scatter Diagram. The resulting 'snowflake' plot shows a pattern of spots and lines, which is interpretable in terms of the functional circuitry among teh neurons. Illustrations are given of the snowflakes produced by a variety of three-neuron circuits, which may serve as a preliminary catalog of snowflake types for interpretation of experimental data.
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Pairs of neurons which inhibit each other can produce regular alternating bursts of impulses if they also exhibit postinhibitory rebound (PIR). Computer studies show that stable patterns occur spontaneously in systems of pacemaker neurons with PIR, and can be triggered in systems of nonpacemakers without requiring tonic excitation. The repetition rates of these patterns are determined largely by the PIR parameters. The patterns resist perturbation by phasic synaptic inputs, but can be modulated or turned off by tonic inputs. One pair of PIR neurons can be entrained by another pair with a different repetition rate to produce more complex firing patterns.
We describe a statistical technique, the joint peristimulus time (PST) scatter diagram, for the analysis of data from simultaneously recorded neurons subjected to repeated stimulation. Distinguishable features in the scatter diagram are related to effects of the stimulus on the observed neurons and to functional relations among the neurons. Properties of this measure and its variants are described and practical aspects of its application to experimental data are discussed.
The influence of basic open-loop synaptic connections on the firing of simultaneously recorded neurons has been investigated with auto- and cross-correlation histograms, using experimental records and computer simulations. The basic connections examined were direct synaptic excitation, direct synaptic inhibition, and shared synaptic input. Each type of synaptic connection produces certain characteristic features in the cross-correlogram depending on the properties of the synapse and statistical features in the firing pattern of each neuron. Thus, empirically derived cross-correlation measures can be interpreted in terms of the underlying physiological mechanisms. Their potential uses and limitations in the detection and identification of synaptic connections between neurons whose extracellularly recorded spike trains are available are discussed.
A new kind of statistical display, the joint peri-stimulus-time scatter diagram, facilitates the analysis and interpretation of two or more simultaneously recorded trains of action potentials. The display is a generalization of the cross correlation and the peri-stimulus-time histogram, and it reflects specific underlying neuronal interactions. The technique yields quantitative measures of interaction in terms of effectiveness of synaptic connections.
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In a study of integration at the single neuron level, the relationships between the postsynaptic membrane potential and the presynaptic spike train were analyzed. Fluctuations in membrane potential of neurons in the visceral ganglion of Aplysia were measured and described by histograms. The histogram estimates the probability density function of the membrane potential. Comparisons were made among histograms when there was no synaptic input, and when there was a single input in which variations were made in the PSP (postsynaptic potential) sign, i.e. excitatory or inhibitory, and arrival statistics, e.g. slow or fast, regular, Poisson-like, or patterned. This was examined in cells where the membrane potential was constant and in cells in which there was spontaneous pacemaker activity. The form of the histogram depended on whether the neuron was spontaneously quiescent or a pacemaker, or whether it received presynaptic input and, if it did, on the sign and temporal characteristics of such input. From such histograms the mean firing rate of output spike trains can be predicted; additional information of a temporal nature is required, however, to predict features of the interval structure of the output train. Suggestions are made concerning the way the nervous system might utilize the information summarized in the membrane potential histogram.
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.
The statistical analysis of two simultaneously observed trains of neuronal spikes is described, using as a conceptual framework the theory of stochastic point processes.The first statistical question that arises is whether the observed trains are independent; statistical techniques for testing independence are developed around the notion that, under the null hypothesis, the times of spike occurrence in one train represent random instants in time with respect to the other. If the null hypothesis is rejected-if dependence is attributed to the trains-the problem then becomes that of characterizing the nature and source of the observed dependencies. Statistical signs of various classes of dependencies, including direct interaction and shared input, are discussed and illustrated through computer simulations of interacting neurons. The effects of nonstationarities on the statistical measures for simultaneous spike trains are also discussed. For two-train comparisons of irregularly discharging nerve cells, moderate nonstationarities are shown to have little effect on the detection of interactions.Combining repetitive stimulation and simultaneous recording of spike trains from two (or more) neurons yields additional clues as to possible modes of interaction among the monitored neurons; the theory presented is illustrated by an application to experimentally obtained data from auditory neurons.A companion paper covers the analysis of single spike trains.
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A number of speculations have been made on the functional role of dendritic spines. Some emphasize that a spine modulates the effect of a chemical synapse on the spine head. Others propose that spines isolate neighboring synapses from each others' effects. Still others suggest that spines play a role in short- or long-term plasticity, while others deny any functional role for spines at all. This paper brings some quantitative calculations to bear on these questions. In contrast to previous studies of the steady-state voltage attenuation in dendrites having spines, our calculations predict the voltage transient throughout a dendrite due to activation of a chemical synapse on a spine-head, causing a time-dependent postsynaptic conductance change associated with a depolarizing reversal potential. We assume passive membrane in the spine and the dendrite. Computations were performed using a compartmental model of a long dendrite and a single spine, having parameters described by Jack et al. (1975). Voltage-divider approximations to the spine-neck were compared with direct compartmental models and with eigenfunction expansions to check the validity of the numerical integrations. In the spine-head, a pronounced transient depolarization is produced, more than twice that predicted by Jack et al. (1975) for steady-state current injection. The EPSP amplitude at the base of the spine was much smaller, and was slightly reduced by placing the synapse on the head of the spine rather than on the dendritic shaft.(ABSTRACT TRUNCATED AT 250 WORDS)