A neural circuit which exhibits some features of epileptic attacks

A neural model based on a generalization of a model proposed in 1938 in the first edition of the author'sMathematical Biophysics (Chicago: Univ. of Chicago Press) is described. It possesses the property that due to some endogenous or exogenous stimulus, which may be of random nature, a pathway may suddenly begin to fire spontaneously. This spontaneous firing may either gradually spread over other pathways and eventually cease, or it may remain localized within one or a few pathways and then cease. Which of the two types of events occurs depends on the values of a number of parameters. The case of spreading reminds one of Jacksonian epilepsy.     

Implementation of a genetic logic circuit: bio-register

We introduce an idea of synthesizing a class of genetic registers based on the existing sequential biological circuits, which are composed of fundamental biological gates. In the renowned literature, biological gates and genetic oscillator have been unveiled and experimentally realized in recent years. These biological circuits have formed a basis for realizing a primitive biocomputer. In the traditional computer architecture, there is an intermediate load-store section, i.e. a register, which serves as a part of the digital processor. With which, the processor can load data from a larger memory into it and proceed to conduct necessary arithmetic or logic operations. Then, manipulated data are stored back to the memory by instruction via the register. We propose here a class of bio-registers for the biocomputer. Four types of register structures are presented. In silicon experiments illustrate results of the proposed design.     

A circuit logic for sexually shared and dimorphic aggressive behaviors in Drosophila

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Opponent inhibition: a developmental model of layer 4 of the neocortical circuit.

We model the development of the functional circuit of layer 4 (the input-recipient layer) of cat primary visual cortex. The observed thalamocortical and intracortical circuitry codevelop under Hebb-like synaptic plasticity. Hebbian development yields opponent inhibition: inhibition evoked by stimuli anticorrelated with those that excite a cell. Strong opponent inhibition enables recognition of stimulus orientation in a manner invariant to stimulus contrast. These principles may apply to cortex more generally: Hebb-like plasticity can guide layer 4 of any piece of cortex to create opposition between anticorrelated stimulus pairs, and this enables recognition of specific stimulus patterns in a manner invariant to stimulus magnitude. Properties that are invariant across a cortical column are predicted to be those shared by opponent stimulus pairs; this contrasts with the common idea that a column represents cells with similar response properties.     

Stabilization of bimanual coordination due to active interhemispheric inhibition: a dynamical account

Based on recent brain-imaging data and congruent theoretical insights, a dynamical model is derived to account for the patterns of brain activity observed during stable performance of bimanual multifrequency patterns, as well as during behavioral instabilities in the form of phase transitions between such patterns. The model incorporates four dynamical processes, defined over both motor and premotor cortices, which are coupled through inhibitory and excitatory inter- and intrahemispheric connections. In particular, the model underscores the crucial role of interhemispheric inhibition in reducing the interference between disparate frequencies during stable performance, as well as the failure of this reduction during behavioral transitions. As an aside, the model also accounts for in- and antiphase preferences during isofrequency movements. The viability of the proposed model is illustrated by magnetoencephalographic signals that were recorded from an experienced subject performing a polyrhythmic tapping task that was designed to induce transitions between multifrequency patterns. Consistent with the models dynamics, contra- and ipsilateral cortical areas of activation were frequency- and phase-locked, while their activation strength changed markedly in the vicinity of transitions in coordination.     

A fuzzy logic model of fracture healing

A quantitative biomechanical model describes the tissue transformation during healing of a transverse osteotomy of a sheep metatarsal. The model predicts bridging of the bone ends through cartilage, followed by the growth of a callus cuff, and finally, the resorption of callus after ossification of the interfragmentary gap. We suggest bone density or the modulus of elasticity do not sufficiently characterize healing tissue for predictive purposes. In addition to the stimulus reflected by strain energy density we introduce a new osteogenic factor based upon stress gradients and which predicts areas of a high osteogenic capacity. Our model distinguishes three basic types of tissue, namely bone, cartilage and fibrous tissue. A fuzzy controller is proposed to model the tissue reaction. A set of fuzzy rules derived from medical knowledge has been implemented to describe tissue transformation such as intramembraneous or chondral ossification, atrophy or destruction. Fuzzy logic is able to model tissue transformation processes within the numerical simulation of remodeling processes. This approach improves the simulation tools and affords the potential to optimize planning of animal experiments and conduct parametric studies.     

A ternary logic model for recurrent neuromime networks with delay

 In contrast to popular recurrent artificial neural network (RANN) models, biological neural networks have unsymmetric structures and incorporate significant delays as a result of axonal propagation. Consequently, biologically inspired neural network models are more accurately described by nonlinear differential-delay equations rather than nonlinear ordinary differential equations (ODEs), and the standard techniques for studying the dynamics of RANNs are wholly inadequate for these models. This paper develops a ternary-logic based method for analyzing these networks. Key to the technique is the realization that a nonzero delay produces a bounded stability region. This result significantly simplifies the construction of sufficient conditions for characterizing the network equilibria. If the network gain is large enough, each equilibrium can be classified as either asymptotically stable or unstable. To illustrate the analysis technique, the swim central pattern generator (CPG) of the sea slug Tritonia diomedea is examined. For wide range of reasonable parameter values, the ternary analysis shows that none of the network equilibria are stable, and thus the network must oscillate. The results show that complex synaptic dynamics are not necessary for pattern generation. Received: 15 June 1994/Accepted in revised form: 10 February 1995     

A retinal circuit model accounting for wide-field amacrine cells

In previous experimental studies on the visual processing in vertebrates, higher-order visual functions such as the object segregation from background were found even in the retinal stage. Previously, the “linear–nonlinear” (LN) cascade models have been applied to the retinal circuit, and succeeded to describe the input-output dynamics for certain parts of the circuit, e.g., the receptive field of the outer retinal neurons. And recently, some abstract models composed of LN cascades as the circuit elements could explain the higher-order retinal functions. However, in such a model, each class of retinal neurons is mostly omitted and thus, how those neurons play roles in the visual computations cannot be explored. Here, we present a spatio-temporal computational model of the vertebrate retina, based on the response function for each class of retinal neurons and on the anatomical inter-cellular connections. This model was capable of not only reproducing the spatio-temporal filtering properties of the outer retinal neurons, but also realizing the object segregation mechanism in the inner retinal circuit involving the “wide-field” amacrine cells. Moreover, the first-order Wiener kernels calculated for the neurons in our model showed a reasonable fit to the kernels previously measured in the real retinal neuron in situ.     

A model cortical circuit for the storage of temporal sequences

Despite the fact that temporal information processing is of particular significance in biological memory systems, not much has yet been explored about how these systems manage to store temporal information involved in sequences of stimuli. A neural network model capable of learning and recalling temporal sequences is proposed, based on a neural mechanism in which the sequences are expanded into a series of periodic rectangular oscillations. Thus, the mathematical framework underlying the model, to some extent, is concerned with the Walsh function series. The oscillatory activities generated by the interplay between excitatory and inhibitory neuron pools are transmitted to another neuron pool whose role in learning and retrieval is to modify the rhythms and phases of the rectangular oscillations. Thus, a basic functional neural circuit involves three different neuron pools. The modifiability of rhythms and phases is incorporated into the model with the aim of improving the quality of the retrieval. Numerical simulations were conducted to show the characteristic features of the learning as well as the performance of the model in memory recall.     

The binding of calcium to fibrinogen: some structural features.

Experiments are described which suggest that structural features are related to the existence of three high affinity calcium-binding sites in the fibrinogen molecule. The circular dichroism spectra analysis shows that the binding of calcium to this protein does not entail an overall conformational change. However several calcium-induced protective effects may be observed: 1. At pH 5.0 calcium-free fibrinogen is slightly acid-denatured. This denaturation is counteracted by the presence of calcium, whereas magnesium ions have no effect. 2. A temperature transition shift of 3 degrees C is measured in the presence of bound calcium during thermal denaturation, whereas magnesium ions have no effect. 3. Resistance to proteolysis by plasmin is observed when calcium is bound to fibrinogen. The velocity of the splitting of the earliest plasmin-succeptible bonds is reduced in the presence of calcium, whereas magnesium ions have no effect. It can be concluded from these results that the calcium binding centers are located in a more or less flexible zone of the molecule probably involving the C-terminal part of the Aalpha chain. And that the calcium divalent cation stabilizes a more compact structure of the fibrinogen molecule.     

A corticothalamic circuit model for sound identification in complex scenes

The identification of the sound sources present in the environment is essential for the survival of many animals. However, these sounds are not presented in isolation, as natural scenes consist of a superposition of sounds originating from multiple sources. The identification of a source under these circumstances is a complex computational problem that is readily solved by most animals. We present a model of the thalamocortical circuit that performs level-invariant recognition of auditory objects in complex auditory scenes. The circuit identifies the objects present from a large dictionary of possible elements and operates reliably for real sound signals with multiple concurrently active sources. The key model assumption is that the activities of some cortical neurons encode the difference between the observed signal and an internal estimate. Reanalysis of awake auditory cortex recordings revealed neurons with patterns of activity corresponding to such an error signal.     

A kinetic model for surfactant inhibition of pentachlorophenol biodegradation

A kinetic model is used to describe the effect of the nonionic surfactant Tergitol NP-10 (TNP10) on pentachlorophenol (PCP) biodegradation by Sphingomonas chlorophenolica sp. strain RA2. Different initial biomass to initial substrate ratios ranging from 13 to 418 were tested with 23 TNP10 concentrations ranging from 0 to 1500 mg/L. Tests were also conducted at 10 degrees C and 20 degrees C. No PCP biodegradation inhibition was observed at concentrations below the critical micelle concentration (CMC) of 50 mg/L. TNP10 concentrations above 100 to 200 mg/L were increasingly inhibitory to PCP biodegradation rates. This inhibition was best described by the Monod kinetic equation wherein the effect of TNP10 inhibition is reflected in the half-saturation constant (Ks). The value of the Ks increased from between 1.5 and 13.5 mg/L with no surfactant present to 44 to 131 mg/L at 1000 mg/L TNP10. Using a standard competitive inhibition approach, the inhibition constant for TNP10 was approximately 100 mg/L at both 10 degrees C and 20 degrees C.     

A model to account for the elastic element in muscle crossbridges in terms of a bending myosin rod

We advance a structural model to account for the rapid elastic element seen in mechanical transient experiments on vertebrate skeletal muscle (A.F. Huxley & Simmons 1971 Nature, Lond. 233, 533-538). In contrast to other crossbridge models, ours does not envisage a myosin rod made up of two rigid portions connected by a hinge, but rather a gradually bending rod portion connecting the heads to the thick filament shaft. We propose that, in relaxed muscle, the subfragment 2 (S2) portion of the myosin rod is bound to the thick filament shaft by ionic interactions analogous to those between the light meromyosin (LMM) portions of the rod that constitute the body of the shaft. These interactions probably involve the alternating zones of positive and negative charge seen in myosin rod amino acid sequences. As the crossbridge cycle that generates tension begins, we propose that part of S2 detaches from the thick filament shaft and bends to enable the myosin head to attach to actin. When tension develops in the crossbridge, the S2 is straightened and more of it becomes detached from the shaft so that the junction between S2 and the myosin heads moves 3-4 nm axially. As tension declines at the end of the crossbridge stroke, we propose that S2 rebinds to the thick filament shaft and that this provides the restoring force to return the junction of the heads and S2 to its original axial position. Thus this movement would have the characteristics of an elastic element; detailed calculations indicate that it would have properties similar to those observed experimentally. Furthermore, this model can account for the radial attractive force seen in rigor and in contracting muscle, the decrease in stiffness when interfilament spacing is increased in skinned muscle, and the increased rate of proteolysis observed at the S2-LMM junction in contracting muscle.