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Biomedical subjects

F J Varela

Publications and source records attributed to F J Varela.

At least 19 recordsLinked to original sources
PubMed1995

Natural tolerance in a simple immune network.

The following basic question is studied here: In the relatively stable molecular environment of a vertebrate body, can a dynamic idiotypic immune network develop a natural tolerance to endogenous components? The approach is based on stability analyses and computer simulation using a model that takes into account the dynamics of two agents of the immune system, namely B-lymphocytes and antibodies. The study investigates the behavior of simple immune networks in interaction with an antigen whose concentration is held constant as a function of the symmetry properties of the connectivity matrix of the network. Current idiotypic network models typically become unstable in the presence of this type of antigen. It is shown that idiotypic networks of a particular connectivity show tolerance towards auto-antigen without the need for ad hoc mechanisms that prevent an immune response. These tolerant network structures are characterized by aperiodic behavior in the absence of auto-antigen. When coupled to an auto-antigen, the chaotic attractor degenerates into one of several periodic ones, and at least one of them is stable. The connectivity structure needed for this behavior allows the system to adopt particular dynamic concentration patterns which do not lead to an unbounded immune response. Possible implications for the understanding of autoimmune disease and its treatment are discussed.

Animals↗
PubMed1995

Resonant cell assemblies: a new approach to cognitive functions and neuronal synchrony.

This paper presents a novel reading of ideas on temporal binding as a key for cognitive operations by means of fast (gamma band) phase synchrony. We advocate a view of binding of widely distributed cell assemblies transiently locked in a neural hypergraph which serves as a reference point to incorporate or interpret other less coherent concurrent neural events. The paper traces in some detail the empirical evidence concerning the gamma binding process and presents some implications for the constitution of a unified cognitive-mental space.

Animals↗
PubMed1993

Visually triggered neuronal oscillations in the pigeon: an autocorrelation study of tectal activity.

In this study we describe visually triggered gamma oscillations in the optic tectum of awake pigeons. This study was motivated by the potential relevance of synchronous oscillatory responses in perceptual binding in a laminated structure other than the mammalian neocortex. Tectal responses were recorded as local field potential and multiunit activity by differential filtering. The local field potential was analysed by computing its autocorrelation function and spectral power with a moving window applied to single response sweeps. The temporal structure of the spike trains was evaluated by computing averaged autocorrelograms. A damped sine wave function was fitted to the autocorrelograms in order to quantify the degree of oscillation of both signals. Epochs of significant oscillatory activity were observed in the local field potential in 60% of the trials (n = 39). In all trials, significant oscillations occupied approximately 10% of the time the stimulus was present. The oscillatory events in both the local field potential and the multiunit activity had frequencies in the range of 20-50 Hz. It is important to emphasize the great variability in the frequency and in the probability of occurrence of the oscillatory responses from trial to trial, which makes the oscillatory behaviour of the tectal activity highly non-stationary. The oscillatory activity we describe in the avian tectum has characteristics similar to those reported in the mammalian neocortex. These findings from a fully awake animal strengthen the universality of oscillations as a possible carrier for synchronization of activity in the constitution of neuronal assemblies.

Action Potentials↗
PubMed1993

Selection of the expressed B cell repertoire by infusion of normal immunoglobulin G in a patient with autoimmune thyroiditis.

In the present study we have analyzed the changes in the expressed antibody repertoire and in temporal fluctuations of antibody levels in serum that followed infusion of normal IgG (IVIg) in a patient with autoimmune thyroiditis. Administration of IVIg resulted in the stimulation of IgM production, in alterations of expressed antibody activity in serum that could not merely be accounted for by the passive transfer of antibody specificities contained in IVIg, in transient down-regulation of B cells clones expressing a specific disease-related idiotype and in the increase in serum in recipient's autoantibodies specifically reactive with F(ab')2 fragments of IVIg. In addition, infusion of IVIg shifted the pattern of spontaneous fluctuations of autoantibody activities in the patient's serum from a pattern indicative of disconnected events in the immune network to a pattern similar to that which is consistently observed in healthy controls. These results suggest that normal IgG may modulate autoreactivity by selecting expressed antibody repertoire through V region-dependent interactions with antibodies.

Adult↗
PubMed1993

A dynamical analysis of oscillatory responses in the optic tectum.

Multi-unit recordings from the optic tectum of an awake pigeon displaying oscillatory behavior evoked by visual stimulus are highly non-stationary and contain a broad band of frequencies under a time-window analysis. Here we extend these observations by a non-linear dynamical analysis of these oscillatory signals (local fields potentials) in successive epochs during background activity and visual responses. Two numerical estimates have been obtained from the original data every 200 ms: (1) correlation dimension and (2) non-linear forecasting of the trajectories. Results from eight different recording sites analyzed are consistent and indicate, in the average, an increase in complexity of the signal during the oscillatory periods.

Animals↗
PubMed1992

Color mixing in the pigeon (Columba livia) II: A psychophysical determination in the middle, short and near-UV wavelength range.

Pigeons were trained to discriminate between spectral lights and additive mixtures in the 350-560 nm spectral range using a successive "autoshaping" discrimination procedure [introduced in Palacios, Martinoya, Bloch & Varela, Vision Research, 30, 587-596 (1990)]. Dichromatic mixtures were found in the short and near UV region, but not in the middle-wave region. Our results suggest that color vision in the pigeon involves the active participation of five different primary mechanisms, which are differentially active in the yellow- and red-sensitive retinal fields.

Animals↗
PubMed1991

Morphogenesis in shape-space. Elementary meta-dynamics in a model of the immune network.

A unique feature of the immune system is that it possesses meta-dynamics: the process governing the removal of certain clones from the active population and the recruitment of new clones from the pool of lymphocytes freshly produced by the bone marrow. In this paper, we present a computer model which focuses on those aspects of the system that characteristically derive from the meta-dynamics as such. We observe that when a region of shape-space is densely populated, there is an emergence of dynamically quasi-stable configurations. Moreover, when the system develops in the presence of permanent self-antigens, the latter are systematically incorporated into such coherent configurations. We conclude that the meta-dynamics of the biological immune system may be such that it gives rise to the emergence of a connected, self-sustaining network that we call the Central Immune System: a coherent self-identity which incorporates the molecules of the somatic self and, more generally, reflects the history of its own development.

Autoantigens↗
PubMed1991

A frequency view of colour: measuring the human sensitivity to square-wave spectral power distributions.

We have measured the chromatic threshold sensitivity to stimuli with spectral composition determined by a periodic function of energy over wavelength. This approach is analogous to frequency studies of spatial vision for the study of colour. A device was constructed permitting the synthesis of illuminants over the entire visible range (400-700 nm) in which phase, frequency and amplitude can be independently controlled. We have used 12 frequencies of square-wave functions (from 0.5 to 3.6 cycles/300 nm) and seven values of phase (between 0 degrees and 180 degrees) to obtain the contrast sensitivity function of the chromatic system in three normal trichromats. The results show maximum sensitivity around 1.5 cycles/300 nm and a high-frequency cut-off at 3.6 cycles/300 nm. These empirical values are compared with the predictions obtained from three current psychophysical models of opponent-colour process.

Biophysical Phenomena↗
PubMed1991

On mental rotations and cortical activity patterns. A linear representation is still wanted.

Carlton (1988) has proposed an attractive hypothesis to link perceived visual images to brain electrical patterns via a linear representation of the Euclidean group onto an appropriate functional space. We show that the construction she proposes is (1) biologically restrictive, and (2) cannot be completed in the desired way. We conclude by presenting other possible means to pursue Carlton's approach.

Depth Perception↗
PubMed1991

Second generation immune networks.

Network approaches have had little impact on immunology because they have addressed the wrong questions. They have concentrated on the regulation of clonal immune responses rather than on the supraclonal properties of the immune system that emerge from its network organization, such as natural tolerance and memory. Theoretical advances, observations in unimmunized mice and humans, and the success of novel therapeutics in autoimmune diseases have recently promoted a new burst of research on the structure, temporal dynamics and metadynamical plasticity of immune networks.

Animals↗
PubMed1991

[Psychophysical study of the chromatic discrimination in pigeons after lesions of thalamic nuclei Rotundus (RT) and Geniculatus Lateralis ventralis (GLv)].

The discrimination threshold at 510 and 640 nm has been measured before and after the bilateral lesion with kaïnic acid of two main thalamic structures: the nucleus rotundus (Rt) and the nucleus geniculatus lateralis ventralis (GLv). When the lesion destroys the GLv and the lower part of the Rt, thresholds increase followed by a progressive recuperation. In contrast, when the Rt lesion is complete, and whether the GLv is touched or not, the threshold increase is both higher and does not come down to the pre-operatory levels even after 15 post-operatory sessions.

Animals↗
PubMed1990

Dynamics of a class of immune networks. I. Global stability of idiotype interactions.

This paper establishes the conditions under which a class of differential equations which appear in the study of immune systems (Varela et al., 1988a, In: Theoretical Immunology Part II. New Jersey: Addison Wesley), are globally stable. This is proved by adapting a Liapunov functional originally proposed by Cohen & Grossberg (1983, IEEE Transac SMC 13, 815-826) for competitive systems. The global stability thus obtained is valid on the fast time scale where only idiotypic interactions are relevant, thus excluding both lymphocyte proliferation processes and repertoire change via recruitment from immature bone marrow B cells.

Animals↗
PubMed1990

Dynamics of a class of immune networks. II. Oscillatory activity of cellular and humoral components.

Simulations show that for a certain range of its free parameters, a model of the immune network including both cellular and humoral components is capable of self-sustained oscillations. The model also possesses a number of fixed points which appear to be unstable. These results, taken together, suggest the hypothesis that the immune network may be able to sustain a non-degenerate diversity of active clones which are actively connected to each other only on condition that the activities of these clones are oscillatory.

Animals↗
PubMed1990

Color mixing in the pigeon. A psychophysical determination in the longwave spectral range.

Pigeons were trained to discriminate between spectral lights and additive mixtures in the 580-640 nm range. Two behavioral procedures were used: (I) a simultaneous instrumental discrimination and (II) successive "autoshaping" discrimination. Pigeons were able to make color mixture matches within this spectral range with satisfactory precision. Matchings determined by the animal correspond well to those predicted on the basis of the spectral sensitivities of two (or even three) pigment-droplet combinations present in the pigeon retina.

Animals↗
PubMed1989

The relationship between connectivity and tolerance as revealed by computer simulation of the immune network: some lessons for an understanding of autoimmunity.

According to a classical, antigen-driven view of the immune system, autoimmunity is due to the presence of self-reactive lymphocyte clones which have not been eliminated. However, computer simulations of the immune network show that the greater the degree of connectivity of a clone, the greater its degree of tolerance to chronic antigenic stimulation. This tolerance does not correspond to an absence of response on the part of the system as a whole. On the contrary, stimulation by a 'tolerogenic antigen' results in widespread modification and overall activation of the whole network. This suggests that on an autopoietic network view of the immune system, autoimmunity arises not because of the presence of self-reactive clones, which is completely normal, but because such clones are inadequately connected to the network. This amounts to a complete reversal in perspective, whose significance for the clinical treatment of autoimmunity and the future of immunology is discussed.

Animals↗
PubMed1989

Exploring the meaning of connectivity in the immune network.

It is suggested that the immune network possesses a distinct internal structure, such that B-lymphocyte clones fall into four categories: 1) A multi-affinity or "sticker" group A, containing all the immunoglobulins with auto-affinity, and generally having affinity for nearly all the other immunoglobulins; 2) and 3) Two "mirror" groups B and C, characterized by the fact that there is virtually no within-group affinity; the affinities between B and C can be arranged co-linearly so that a clone from group B has affinity with its opposite number(s) in group C; 4) A fourth group of low affinity, each clone having affinity only with clones from group A. Computer simulations show that this way of analyzing the connectivity of the network makes sense (a) in relation to the stereochemical origins of affinity; and (b) in relation to the dynamical behavior of the clones in a functioning network.

Animals↗
PubMed1988

Frontal and lateral visual system in birds. Frontal and lateral gaze.

Birds exhibit a variable retinal organization in terms of foveas and areas of high cell density. The distribution of these retinal structures in different species does not follow phylogenetic lines. In order to study this phenomenon, we presented chickens and pigeons with a luminous bar that could be moved at different speeds and directions in the visual field and could be located at various distances from the animal; head movements were monitored during the presentations. The results show that for a static or slow-moving stimulus the birds adopted a frontal gaze that stabilized the image in the retina, and for a fast-moving stimulus they adopted a lateral gaze that allowed the image to move across the retina. These results reveal that: (a) these two ways of looking correlate with the retinal anatomy, not with the phylogeny, of the species, and (b) these two ways of looking reflect two different sensorimotor systems that involve different anatomical features and neurophysiological properties of the visual system in birds.

Animals↗