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Biomedical subjects

F Gabbiani

Publications and source records attributed to F Gabbiani.

At least 19 recordsLinked to original sources

Differential coding of humoral stimuli by timing and amplitude of intracellular calcium spike trains.

The ubiquitous Ca2(+)-phosphoinositide pathway transduces extracellular signals to cellular effectors. Using a mathematical model, we simulated intracellular Ca2+ fluctuations in hepatocytes upon humoral stimulation. We estimated the information encoded about random humoral stimuli in these Ca2+ spike trains using an information-theoretic approach based on stimulus estimation methods. We demonstrate accurate transfer of information about random humoral signals with low temporal cutoff frequencies. In contrast, our results suggest that high-frequency stimuli are poorly transduced by the transmembrane machinery. We found that humoral signals are encoded in both the timing and amplitude of intracellular Ca2+ spikes. The information transmitted per spike is similar to that of sensory neuronal systems, in spite of several orders of magnitude difference in firing rate.

Action Potentials↗

Visual categorization and object representation in monkeys and humans.

We investigated the influence of a categorization task on the extraction and representation of perceptual features in humans and monkeys. The use of parameterized stimuli (schematic faces and fish) with fixed diagnostic features in combination with a similarity-rating task allowed us to demonstrate perceptual sensitization to the diagnostic dimensions of the categorization task for the monkeys. Moreover, our results reveal important similarities between human and monkey visual subordinate categorization strategies. Neither the humans nor the monkeys compared the new stimuli to class prototypes or based their decisions on conditional probabilities along stimulus dimensions. Instead, they classified each object according to its similarity to familiar members of the alternative categories, or with respect to its position to a linear boundary between the learned categories.

Animals↗

Invariance of angular threshold computation in a wide-field looming-sensitive neuron.

The lobula giant motion detector (LGMD) is a wide-field bilateral visual interneuron in North American locusts that acts as an angular threshold detector during the approach of a solid square along a trajectory perpendicular to the long axis of the animal (Gabbiani et al., 1999a). We investigated the dependence of this angular threshold computation on several stimulus parameters that alter the spatial and temporal activation patterns of inputs onto the dendritic tree of the LGMD, across three locust species. The same angular threshold computation was implemented by LGMD in all three species. The angular threshold computation was invariant to changes in target shape (from solid squares to solid discs) and to changes in target texture (checkerboard and concentric patterns). Finally, the angular threshold computation did not depend on object approach angle, over at least 135 degrees in the horizontal plane. A two-dimensional model of the responses of the LGMD based on linear summation of motion-related excitatory and size-dependent inhibitory inputs successfully reproduced the experimental results for squares and discs approaching perpendicular to the long axis of the animal. Linear summation, however, was unable to account for invariance to object texture or approach angle. These results indicate that LGMD is a reliable neuron with which to study the biophysical mechanisms underlying the generation of complex but invariant visual responses by dendritic integration. They also suggest that invariance arises in part from non-linear integration of excitatory inputs within the dendritic tree of the LGMD.

Animals↗

Cultured arterial smooth muscle cells maintain distinct phenotypes when implanted into carotid artery.

Cultured arterial smooth muscle cells (SMCs) with distinct phenotypic features have been described by several laboratories; however, it is not presently known whether this phenotypic heterogeneity can be maintained within an in vivo environment. To answer this question, we have seeded into the intima of denuded rat carotid artery 2 SMC populations with well-established distinct biological features, ie, spindle-shaped, not growing in the absence of serum, and well differentiated versus epithelioid, growing in the absence of serum, and relatively undifferentiated, derived from the aortic media of newborn rats (aged 4 days) and old rats (aged >18 months), respectively. We show that these 2 populations maintain their distinct biochemical features (ie, expression of alpha-smooth muscle actin, smooth muscle myosin heavy chains, and cellular retinol binding protein-1) in the in vivo environment. The old rat media-derived SMCs continue to produce cellular retinol binding protein-1 but little alpha-smooth muscle actin and smooth muscle myosin heavy chains, whereas the newborn rat media-derived SMCs continue to express alpha-smooth muscle actin and smooth muscle myosin heavy chains but no cellular retinol binding protein-1. Our results reinforce the notion of arterial SMC phenotypic heterogeneity and suggest that in our model, heterogeneity is controlled genetically and not by the local environment.

Actins↗

Coding efficiency and information rates in transmembrane signaling.

A variety of cell types responds to hormonal stimuli by repetitive spikes in the intracellular concentration of calcium ([Ca(2+)](i)) which have been demonstrated to encode information in their frequency, amplitude, and duration. These [Ca(2+)](i)-spike trains are able to specifically regulate distinct cellular functions. Using a mathematical model for receptor-controlled [Ca(2+)](i) oscillations in hepatocytes we investigate the encoding of fluctuating hormonal signals in [Ca(2+)](i)-spike trains. The transmembrane information transfer is quantified by using an information-theoretic reverse-engineering approach which allows to reconstruct the dynamic hormonal stimulus from the [Ca(2+)](i)-spike trains. This approach allows to estimate the accuracy of coding as well as the rate of transmembrane information transfer. We found that up to 87% of the dynamic stimulus information can be encoded in the [Ca(2+)](i)-spike train at a maximum information transfer rate of 1.1 bit per [Ca(2+)](i)-spike. These numerical results for humoral information transfer are in the same order as in a number of sensory neuronal systems despite several orders of magnitude different time scales of operation suggesting a universal principle of information processing in both biological systems.

Action Potentials↗

Robustness and variability of neuronal coding by amplitude-sensitive afferents in the weakly electric fish eigenmannia.

We investigated the variability of P-receptor afferent spike trains in the weakly electric fish, Eigenmannia, to repeated presentations of random electric field AMs (RAMs) and quantified its impact on the encoding of time-varying stimuli. A new measure of spike timing jitter was developed using the notion of spike train distances recently introduced by Victor and Purpura. This measure of variability is widely applicable to neuronal responses, irrespective of the type of stimuli used (deterministic vs. random) or the reliability of the recorded spike trains. In our data, the mean spike count and its variance measured in short time windows were poorly correlated with the reliability of P-receptor afferent spike trains, implying that such measures provide unreliable indices of trial-to-trial variability. P-receptor afferent spike trains were considerably less variable than those of Poisson model neurons. The average timing jitter of spikes lay within 1-2 cycles of the electric organ discharge (EOD). At low, but not at high firing rates, the timing jitter was dependent on the cutoff frequency of the stimulus and, to a lesser extent, on its contrast. When spikes were artificially manipulated to increase jitter, information conveyed by P-receptor afferents was degraded only for average jitters considerably larger than those observed experimentally. This suggests that the intrinsic variability of single spike trains lies outside of the range where it might degrade the information conveyed, yet still allows for improvement in coding by averaging across multiple afferent fibers. Our results were summarized in a phenomenological model of P-receptor afferents, incorporating both their linear transfer properties and the variability of their spike trains. This model complements an earlier one proposed by Nelson et al. for P-receptor afferents of Apteronotus. Because of their relatively high precision with respect to the EOD cycle frequency, P-receptor afferent spike trains possess the temporal resolution necessary to support coincidence detection operations at the next stage in the amplitude-coding pathway.

Action Potentials↗

Computation of object approach by a wide-field, motion-sensitive neuron.

The lobula giant motion detector (LGMD) in the locust visual system is a wide-field, motion-sensitive neuron that responds vigorously to objects approaching the animal on a collision course. We investigated the computation performed by LGMD when it responds to approaching objects by recording the activity of its postsynaptic target, the descending contralateral motion detector (DCMD). In each animal, peak DCMD activity occurred a fixed delay delta (15 </= delta </= 35 msec) after the approaching object had reached a specific angular threshold thetathres on the retina (15 degrees </= thetathres </= 40 degrees). thetathres was independent of the size or velocity of the approaching object. This angular threshold computation was quite accurate: the error of LGMD and DCMD in estimating thetathres (3.1-11.9 degrees) corresponds to the angular separation between two and six ommatidia at each edge of the expanding object on the locust retina. It was also resistant to large amplitude changes in background luminosity, contrast, and body temperature. Using several experimentally derived assumptions, the firing rate of LGMD and DCMD could be shown to depend on the product psi(t - delta). e-alphatheta(t-delta), where theta(t) is the angular size subtended by the object during approach, psi(t) is the angular edge velocity of the object and the constant, and alpha is related to the angular threshold size [alpha = 1/tan(thetathres/2)]. Because LGMD appears to receive distinct input projections, respectively motion- and size-sensitive, this result suggests that a multiplication operation is implemented by LGMD. Thus, LGMD might be an ideal model to investigate the biophysical implementation of a multiplication operation by single neurons.

Animals↗

Encoding and processing of sensory information in neuronal spike trains

Recently, a statistical signal-processing technique has allowed the information carried by single spike trains of sensory neurons on time-varying stimuli to be characterized quantitatively in a variety of preparations. In weakly electric fish, its application to first-order sensory neurons encoding electric field amplitude (P-receptor afferents) showed that they convey accurate information on temporal modulations in a behaviorally relevant frequency range (<80 Hz). At the next stage of the electrosensory pathway (the electrosensory lateral line lobe, ELL), the information sampled by first-order neurons is used to extract upstrokes and downstrokes in the amplitude modulation waveform. By using signal-detection techniques, we determined that these temporal features are explicitly represented by short spike bursts of second-order neurons (ELL pyramidal cells). Our results suggest that the biophysical mechanism underlying this computation is of dendritic origin. We also investigated the accuracy with which upstrokes and downstrokes are encoded across two of the three somatotopic body maps of the ELL (centromedial and lateral). Pyramidal cells of the centromedial map, in particular I-cells, encode up- and downstrokes more reliably than those of the lateral map. This result correlates well with the significance of these temporal features for a particular behavior (the jamming avoidance response) as assessed by lesion experiments of the centromedial map.

Journal Article↗

Feature extraction by burst-like spike patterns in multiple sensory maps.

In most sensory systems, higher order central neurons extract those stimulus features from the sensory periphery that are behaviorally relevant (e.g.,Marr, 1982; Heiligenberg, 1991). Recent studies have quantified the time-varying information carried by spike trains of sensory neurons in various systems using stimulus estimation methods (Bialek et al., 1991; Wessel et al., 1996). Here, we address the question of how this information is transferred from the sensory neuron level to higher order neurons across multiple sensory maps by using the electrosensory system in weakly electric fish as a model. To determine how electric field amplitude modulations are temporally encoded and processed at two subsequent stages of the amplitude coding pathway, we recorded the responses of P-type afferents and E- and I-type pyramidal cells in the electrosensory lateral line lobe (ELL) to random distortions of a mimic of the fish's own electric field. Cells in two of the three somatotopically organized ELL maps were studied (centromedial and lateral) (Maler, 1979; Carr and Maler, 1986). Linear and second order nonlinear stimulus estimation methods indicated that in contrast to P-receptor afferents, pyramidal cells did not reliably encode time-varying information about any function of the stimulus obtained by linear filtering and half-wave rectification. Two pattern classifiers were applied to discriminate stimulus waveforms preceding the occurrence or nonoccurrence of pyramidal cell spikes in response to the stimulus. These signal-detection methods revealed that pyramidal cells reliably encoded the presence of upstrokes and downstrokes in random amplitude modulations by short bursts of spikes. Furthermore, among the different cell types in the ELL, I-type pyramidal cells in the centromedial map performed a better pattern-recognition task than those in the lateral map and than E-type pyramidal cells in either map.

Action Potentials↗

Coding of time-varying hormonal signals in intracellular calcium spike trains.

In a variety of cell types extracellular hormonal stimuli varying in time are transfered across the cell membrane into repetitive spikes of the intracellular calcium concentration ([Ca2+]i). Distinct temporal patterns of [Ca2+]i spikes are capable of regulating the function and structure of target cells. Here, we investigate the ability of transmembrane signaling to encode time-varying hormonal stimulations (bandlimited Gaussian white noise) in a model of receptor-controlled [Ca2+]i oscillations. The encoding of hormonal signals in [Ca2+]i spike trains is quantified by using an information-theoretic approach allowing to estimate the hormonal stimulus from [Ca2+]i spike trains. Our results suggest that intracellular [Ca2+]i spike trains convey faithful information on temporal variations of extracellular hormonal concentrations at scales of 30-200 sec, corresponding to cut-off frequencies between 5 and 30 mHz of the random hormonal stimulation.

Animals↗

Cellular retinol-binding protein-1 is expressed by distinct subsets of rat arterial smooth muscle cells in vitro and in vivo.

Previous work (M.-L. Bochaton-Piallat, P. Ropraz, F. Gabbiani, G. Gabbiani, Arterioscler Thromb Vasc Biol 1996, 16:815-820) has shown that a subset of smooth muscle cell (SMC) clones derived from the normal rat aortic media displays an epithelioid phenotype similar to that of the whole SMC population cultured from the intimal thickening 15 days after endothelial injury (IT-15). We show here that the whole IT-15 SMC population and the epithelioid clones, derived either from the normal media or from the IT-15, express cellular retinol-binding protein-1 (CRBP-1), a protein involved in retinoid metabolism. The expression of CRBP-1 is accompanied by the expression of cytokeratin 8. In both whole SMC population cultured from IT-15 and epithelioid clones, retinoic acid modulates the transition from the epithelioid phenotype to the spindle phenotype, typical of whole SMC populations cultured from the rat normal aortic media. Moreover, after endothelial injury in vivo, a CRBP-1 expressing SMC subset appears transiently in the IT and disappears, allegedly by apoptosis, when re-endothelialization takes place. Our results suggest that the expression of CRBP-1 is a marker of arterial SMC activation after endothelial injury in vivo and that CRBP-1 and probably retinoids participate in this process.

Animals↗

From stimulus encoding to feature extraction in weakly electric fish.

Animals acquire information about sensory stimuli around them and encode it using an analogue or a pulse-based code. Behaviourally relevant features need to be extracted from this representation for further processing. In the electrosensory system of weakly electric fish, single P-type electroreceptor afferents accurately encode the time course of random modulations in electric-field amplitude. We applied a stimulus estimation method and a signal-detection method to both P-receptor afferents and their targets, the pyramidal cells in the electrosensory lateral-line lobe. We found that although pyramidal cells do not accurately convey detailed information about the time course of the stimulus, they reliably encode up- and downstrokes of random modulations in electric-field amplitude. The presence of such temporal features is best signalled by short bursts of spikes, probably caused by dendritic processing, rather than by isolated spikes. Furthermore, pyramidal cells outperform P-receptor afferents in signalling the presence of temporal features in the stimulus waveform. We conclude that the sensory neurons are specialized to acquire information accurately with little processing, whereas the following stage extracts behaviourally relevant features, thus performing a nonlinear pattern-recognition task.

Action Potentials↗

Coding of time-varying electric field amplitude modulations in a wave-type electric fish.

1. The coding of time-varying electric fields in the weakly electric fish, Eigenmannia, was investigated in a quantitative manner. The activity of single P-type electroreceptor afferents was recorded while the amplitude of an externally applied sinusoidal electric field was stochastically modulated. The amplitude modulation waveform (i.e., the stimulus) was reconstructed from the spike trains by mean square estimation. 2. From the stimulus and the reconstructions we calculated the following: 1) the signal-to-noise ratio and thus an effective temporal bandwidth of the units; 2) the coding fraction, i.e., a measure of the fraction of the time-varying stimulus encoded in single spike trains; and 3) the mutual information provided by the reconstructions about the stimulus. 3. Signal-to-noise ratios as high as 7:1 were observed and the bandwidth ranged from 0 up to 200 Hz, consistent with the limit imposed by the sampling theorem. Reducing the cutoff frequency of the stimulus increased the signal-to-noise ratio at low frequencies, indicating a nonlinearity in the receptors' response. 4. The coding fraction and the rate of mutual information transmission increased in parallel with the standard deviation (i.e., the contrast) of the stimulus as well as the mean firing rate of the units. Significant encoding occurred 20-40 Hz above the spontaneous discharge of a unit. 5. When the temporal cutoff frequency of the stimulus was increased between 80 and 400 Hz, 1) the coding fraction decreased, 2) the rate of mutual information transmission remained constant over the same frequency range, and 3) the reconstructed filter changed. This is in agreement with predictions obtained in a simplified neuronal model. 6. Our results suggest that 1) the information transmitted by single spike trains of primary electrosensory afferents to higherorder neurons in the fish brain depends on the contrast and the cutoff frequency of the stimulus as well as on the mean firing rate of the units; and 2) under optimal conditions, more than half of the information about a Gaussian stimulus that can in principle be encoded is carried in single spike trains of P-type afferents at rates up to 200 bits per second.

Action Potentials↗

Phenotypic heterogeneity of rat arterial smooth muscle cell clones. Implications for the development of experimental intimal thickening.

It is well accepted that smooth muscle cells (SMCs) cultured from normal rat arterial media have different morphological and biological features compared with SMCs cultured from experimental intimal thickening (IT) 15 days after endothelial injury. It is not known, however, whether the phenotypic modulation producing IT cells occurs in any medial SMCs or only in a particular SMC subpopulation. To distinguish among these possibilities, the phenotypic features of SMC clones derived from normal adult media and the IT 15 days after endothelial lesion were analyzed according to morphological appearance, replicative activity in the presence and absence of fetal calf serum, and [3H]thymidine incorporation and motile activity; these features were compared with those of the respective SMC parental populations. Two categories of SMC clones predominated: spindle clones, with morphological features similar to those of the parental population from the normal media, and epithelioid clones, with morphological features similar to those of the IT parental population. Both categories were present among clones produced from normal media and IT; however, spindle was more common among normal media clones, and epithelioid, among IT clones. The behavior in vitro was distinct for each category of clones and did not depend on their origin. Our results are compatible with the possibility that the SMC population of IT in vivo derives mainly from SMCs belonging to the category exhibiting epithelioid features in vitro.

Animals↗

Elementary computation of object approach by wide-field visual neuron.

An essential function of the brain is to detect threats, such as those posed by objects or predators on a collision course. A wide-field, movement-sensitive visual neuron in the brain of the locust was studied by presenting simulated approaching, receding, and translating objects. The neuron's responses could be described simply by multiplying the velocity of the image edge (dtheta/dtau) with an exponential function of the size of the object's image on the retina (e-alpha theta). Because this product peaks before the image reaches its maximum size during approach, this neuron can anticipate collision. The neuron's activity peaks approximately when the approaching object reaches a certain angular size. Because this neuron receives distinct inputs about image size and velocity, the dendritic tree of a single neuron may function as a biophysical device that can carry out a multiplication of two independent input signals.

Algorithms↗