Attila Szücs

Synchronous behavior of two coupled electronic neurons

We report on experimental studies of synchronization phenomena in a pair of analog electronic neurons (ENs). The ENs were designed to reproduce the observed membrane voltage oscillations of isolated biological neurons from the stomatogastric ganglion of the California spiny lobster Panulirus interruptus. The ENs are simple analog circuits which integrate four-dimensional differential equations representing fast and slow subcellular mechanisms that produce the characteristic regular/chaotic spiking-bursting behavior of these cells. In this paper we study their dynamical behavior as we couple them in the same configurations as we have done for their counterpart biological neurons. The interconnections we use for these neural oscillators are both direct electrical connections and excitatory and inhibitory chemical connections: each realized by analog circuitry and suggested by biological examples. We provide here quantitative evidence that the ENs and the biological neurons behave similarly when coupled in the same manner. They each display well defined bifurcations in their mutual synchronization and regularization. We report briefly on an experiment on coupled biological neurons and four-dimensional ENs, which provides further ground for testing the validity of our numerical and electronic models of individual neural behavior. Our experiments as a whole present interesting new examples of regularization and synchronization in coupled nonlinear oscillators.

Extended dynamic clamp: controlling up to four neurons using a single desktop computer and interface

The dynamic clamp protocol allows an experimenter to simulate the presence of membrane conductances in, and synaptic connections between, biological neurons. Existing protocols and commercial ADC/DAC boards provide ready control in and between < or =2 neurons. Control at >2 sites is desirable when studying neural circuits with serial or ring connectivity. Here, we describe how to extend dynamic clamp control to four neurons and their associated synaptic interactions, using a single IBM-compatible PC, an ADC/DAC interface with two analog outputs, and an additional demultiplexing circuit. A specific C++ program, DYNCLAMP4, implements these procedures in a Windows environment, allowing one to change parameters while the dynamic clamp is running. Computational efficiency is increased by varying the duration of the input-output cycle. The program simulates < or =8 Hodgkin-Huxley-type conductances and < or =18 (chemical and/or electrical) synapses in < or =4 neurons and runs at a minimum update rate of 5 kHz on a 450 MHz CPU. (Increased speed is possible in a two-neuron version that does not need auxiliary circuitry). Using identified neurons of the crustacean stomatogastric ganglion, we illustrate on-line parameter modification and the construction of three-member synaptic rings.

Applications of the spike density function in analysis of neuronal firing patterns.

Firing rate histogram is a widely used mathematical method for representing the activity of single neurons and small neural networks. Nevertheless, observation of fine temporal modulation or correlations of spike trains might be troublesome if the mean firing rate is low or rapid local changes occur. The spike density function (SDF) obtained by convolving the spike train with smooth and continuous kernel function proves to be a more appropriate approach in characterization of the firing pattern. The resulting time-function is a continuous and derivable one, thus it can be used as a dynamical variable of the neuronal activity. In the present paper applications of SDF in analysis of the firing patterns of Lymnaea neurons are described and its performance is compared to other quantitative methods.Firing rate histogram is a widely used mathematical method for representing the activity of single neurons and small neural networks. Nevertheless, observation of fine temporal modulation or correlations of spike trains might be troublesome if the mean firing rate is low or rapid local changes occur. The spike density function (SDF) obtained by convolving the spike train with smooth and continuous kernel function proves to be a more appropriate approach in characterization of the firing pattern. The resulting time-function is a continuous and derivable one, thus it can be used as a dynamical variable of the neuronal activity. In the present paper applications of SDF in analysis of the firing patterns of Lymnaea neurons are described and its performance is compared to other quantitative methods.

Delayed satiety-like actions and altered feeding microstructure by a selective type 2 corticotropin-releasing factor agonist in rats: intra-hypothalamic urocortin 3 administration reduces food intake by prolonging the post-meal interval.

Brain corticotropin-releasing factor/urocortin (CRF/Ucn) systems are hypothesized to control feeding, with central administration of ‘type 2’ urocortins producing delayed anorexia. The present study sought to identify the receptor subtype, brain site, and behavioral mode of action through which Ucn 3 reduces nocturnal food intake in rats. Non-food-deprived male Wistar rats (n=176) were administered Ucn 3 into the lateral (LV) or fourth ventricle, or into the ventromedial or paraventricular nuclei of the hypothalamus (VMN, PVN) or the medial amygdala (MeA), regions in which Ucn 3 is expressed in proximity to CRF2 receptors. LV Ucn 3 suppressed ingestion during the third–fourth post-injection hours. LV Ucn 3 anorexia was reversed by cotreatment with astressin2-B, a selective CRF2 antagonist and not observed following equimole subcutaneous or fourth ventricle administration. Bilateral intra-VMN and intra-PVN infusion, more potently than LV infusion, reduced the quantity (57–73%) and duration of ingestion (32–68%) during the third–fourth post-infusion hours. LV, intra-PVN and intra-VMN infusion of Ucn 3 slowed the eating rate and reduced intake by prolonging the post-meal interval. Intra-VMN Ucn 3 reduced feeding bout size, and intra-PVN Ucn 3 reduced the regularity of eating from pellet to pellet. Ucn 3 effects were behaviorally specific, because minimal effective anorectic Ucn 3 doses did not alter drinking rate or promote a conditioned taste aversion, and site-specific, because intra-MeA Ucn 3 produced a nibbling pattern of more, but smaller meals without altering total intake. The results implicate the VMN and PVN of the hypothalamus as sites for Ucn 3-CRF2 control of food intake.

Interacting biological and electronic neurons generate realistic oscillatory rhythms.

Small assemblies of neurons such as central pattern generators (CPG) are known to express regular oscillatory firing patterns comprising bursts of action potentials. In contrast, individual CPG neurons isolated from the remainder of the network can generate irregular firing patterns. In our study of cooperative behavior in CPGs we developed an analog electronic neuron (EN) that reproduces firing patterns observed in lobster pyloric CPG neurons. Using a tuneable artificial synapse we connected the EN bidirectionally to neurons of this CPG. We found that the periodic bursting oscillation of this mixed assembly depends on the strength and sign of the electrical coupling. Working with identified, isolated pyloric CPG neurons whose network rhythms were impaired, the EN/biological network restored the characteristic CPG rhythm both when the EN oscillations are regular and when they are irregular.

Reliable circuits from irregular neurons: A dynamical approach to understanding central pattern generators

Central pattern generating neurons from the lobster stomatogastric ganglion were analyzed using new nonlinear methods. The LP neuron was found to have only four or five degrees of freedom in the isolated condition and displayed chaotic behavior. We show that this chaotic behavior could be regularized by periodic pulses of negative current injected into the neuron or by coupling it to another neuron via inhibitory connections. We used both a modified Hindmarsh-Rose model to simulate the neurons behavior phenomenologically and a more realistic conductance-based model so that the modeling could be linked to the experimental observations. Both models were able to capture the dynamics of the neuron behavior better than previous models. We used the Hindmarsh-Rose model as the basis for building electronic neurons which could then be integrated into the biological circuitry. Such neurons were able to rescue patterns which had been disabled by removing key biological neurons from the circuit.

Modulation of voltage-activated ion currents on identified neurons of Helix pomatia L. by interleukin-1

Summary1.The effect of interleukin-1 (IL-1) was studied on voltage-activated ion currents of the identified central neurons ofHelix pomatia L. using a twomicroelectrode voltage clamp. The voltage-activated inward current (ICa) was decreased, whereas the outward current (Inet K) was increased by IL-1.2.IL-1 affects both the transient and the delayed rectifying potassium currents. The IL-1 modulatory effect on the voltage-activated ion currents was voltage and dose dependent. The threshold concentration for IL-1 was 2 U/ml.3.The proposed modulatory effect of IL-1 appears to have more than one site of action on the neuron membrane ion channels.4.Rabbit anti-human IL-1 polyclonal antiserum eliminated the IL-1 effects on the voltage-activated inward and outward currents. This is the first report demonstrating a direct effect of IL-1 modulation of voltage-activated ion currents on neurons of mollusks.

Histological and microarray analysis of the direct effect of water shortage alone or combined with heat on early grain development in wheat (Triticum aestivum)

Based on the in silico analysis of the representation of expressed sequence tags (ESTs) in wheat grain-related cDNA libraries, a specific 15k oligonucleotide microarray has been developed in order to monitor environmental stress-dependent gene expression changes in the wheat caryopses. Using this array, the effect of water withdrawal, with and without additional heat stress, has been investigated during the first five days of kernel development on two wheat cultivars differing in their drought sensitivity. Water shortage affected (more than twofold change) the expression of only 0.5% of the investigated genes. A parallel heat treatment increased the ratio of responding genes to 5-7% because of the temperature stress and/or the increased water deficit because of enhanced evaporation. It could be established that the two cultivars, differing in their long-term adaptation capabilities to drought, responded to the short and direct stress treatments on the same way. In response to the combined drought and heat treatment, the coordinately altered expression of genes coding for storage proteins, enzymes involved in sugar/starch metabolism, histone proteins, heat shock proteins, proteases, tonoplast aquaporins as well as several transcription factors has been observed. These gene expression changes were in agreement with histological data that demonstrated the accelerated development of the embryo as well as the endosperm.

Models Wagging the Dog: Are Circuits Constructed with Disparate Parameters?

In a recent article, Prinz, Bucher, and Marder (2004) addressed the fundamental question of whether neural systems are built with a fixed blueprint of tightly controlled parameters or in a way in which properties can vary largely from one individual to another, using a database modeling approach. Here, we examine the main conclusion that neural circuits indeed are built with largely varying parameters in the light of our own experimental and modeling observations. We critically discuss the experimental and theoretical evidence, including the general adequacy of database approaches for questions of this kind, and come to the conclusion that the last word for this fundamental question has not yet been spoken.

Systemic urocortin 2, but not urocortin 1 or stressin1-A, suppresses feeding via CRF2 receptors without malaise and stress

BACKGROUND AND PURPOSE Infusion of corticotropin‐releasing factor (CRF)/urocortin (Ucn) family peptides suppresses feeding in mice. We examined whether rats show peripheral CRF/Ucn‐induced anorexia and determined its behavioural and pharmacological bases.