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PubMed1990

The effects of position cues on the appearance of stimulus elements in a bistable apparent movement display.

A modified version of the Ternus display was used to assess the relative effects of element position cues on reports of group and end-to-end movement. In this display, two rows of stimulus elements are joined by connecting lines. In one version of the display, the connecting lines remain stationary across frames, facilitating the interpretation that the associated stimulus elements also remain stationary. In another version of the display, one end of the connecting lines shifts horizontally from frame to fame, facilitating the interpretation that the associated stimulus elements have also shifted. The experiment showed that when the connecting lines remain stationary, reports of end-to-end movement increase, regardless of the interstimulus interval (ISI) at which the frames alternate. When the connecting lines shift, reports of group movement increase, regardless of ISI. Theoretical interpretations of the results involving both relatively low-level motion signals and higher order perceptual influences are considered.

Attention↗
PubMed2000

Bistable behavior of inhibitory neurons controlling impulse traffic through the amygdala: role of a slowly deinactivating K+ current.

The intercalated cell masses of the amygdala are clusters of GABAergic neurons located strategically to influence behavioral responsiveness. Indeed, they receive glutamatergic sensory inputs from the basolateral amygdaloid complex and generate feedforward inhibition in neurons of the central amygdala that mediate important components of fear responses. In the present study, using whole-cell recording methods in coronal slices of the guinea pig amygdala, we show that the activity of intercalated neurons is a function of their recent firing history because they express an unusual voltage-dependent K(+) conductance (termed I(SD) for slowly deinactivating). This conductance activates in the subthreshold regime, inactivates in response to suprathreshold depolarizations, and deinactivates very slowly upon return to rest. As a result, after bouts of suprathreshold activity, these cells enter a self-sustaining state of heightened excitability associated with an increased input resistance and a membrane depolarization. In turn, these changes increase the likelihood that ongoing synaptic activity will trigger orthodromic action potentials. However, because each orthodromic spike "renews" the inactivation of I(SD), intercalated cells can remain hyperexcitable for a long time and, via the central amygdaloid nucleus, exert a lasting influence on behavior.

Action Potentials↗
PubMed2001

Perceptually bistable three-dimensional figures evoke high choice probabilities in cortical area MT.

The role of the primate middle temporal area (MT) in depth perception was examined by considering the trial-to-trial correlations between neuronal activity and reported depth sensations. A set of moving random dots portrayed a cylinder rotating about its principal axis. In this structure-from-motion stimulus, the direction of rotation is ambiguous and the resulting percept undergoes spontaneous fluctuations. The stimulus can be rendered unambiguous by the addition of binocular disparities. We trained monkeys to report the direction of rotation in a set of these stimuli, one of which had zero disparity. Many disparity-selective neurons in area MT are selective for the direction of rotation defined by disparity. Across repeated presentations of the ambiguous (zero-disparity) stimulus, there was a correlation between neuronal firing and the reported direction of rotation, as found by Bradley et al. (1998). Quantification of this effect using choice probabilities (Britten et al., 1996) allowed us to demonstrate that the correlation cannot be explained by eye movements, behavioral biases, or attention to spatial location. MT neurons therefore appear to be involved in the perceptual decision process. The mean choice probability (0.67) was substantially larger than that reported for MT neurons in a direction discrimination task (Britten et al., 1996). This implies that MT neurons make a different contribution to the two tasks. For the depth task, either the pool of neurons used is smaller or the correlation between neurons in the pool is larger.

Action Potentials↗
PubMed1980

Bistability in a model of microbial product formation.

A mathematical model of continuous growth of microorganisms and product formation with growth inhibition by the product is presented and investigated. Two stable steady states occur due to the competion of growth and product formation for the same limiting substrate. One stable state is characterized by a high product concentration but low biomass concentration whereas the other state is characterized by the opposite relations. The first steady state is approached by oscillating kinetics. Both phenomena are consistent with frequently observed kinetic instabilities in industrial fermentation processes.

Anti-Bacterial Agents↗
PubMed2004

The role of physical environment on molecular electromechanical switching.

The influences of different physical environments on the thermodynamics associated with one key step in the switching mechanism for a pair of bistable catenanes and a pair of bistable rotaxanes have been investigated systematically. The two bistable catenanes are comprised of a cyclobis(paraquat-p-phenylene) (CBPQT4+) ring, or its diazapyrenium-containing analogue, that are interlocked with a macrocyclic polyether component that incorporates the strong tetrathiafulvalene (TTF) donor unit and the weaker 1,5-dioxynaphthalene (DNP) donor unit. The two bistable rotaxanes are comprised of a CBPQT4+ ring, interlocked with a dumbbell component in which one incorporates TTF and DNP units, whereas the other incorporates a monopyrrolotetrathiafulvalene (MPTTF) donor and a DNP unit. Two consecutive cycles of a variable scan rate cyclic voltammogram (10-1500 mV s(-1)) performed on all of the bistable switches (approximately 1 mM) in MeCN electrolyte solutions (0.1 M tetrabutylammonium hexafluorophosphate) across a range of temperatures (258-303 K) were recorded in a temperature-controlled electrochemical cell. The second cycle showed different intensities of the two features that were observed in the first cycle when the cyclic voltammetry was recorded at fast scan rates and low temperatures. The first oxidation peak increases in intensity, concomitant with a decrease in the intensity of the second oxidation peak. This variation changed systematically with scan rate and temperature and has been assigned to the molecular mechanical movements within the catenanes and rotaxanes of the CBPQT4+ ring from the DNP to the TTF unit. The intensities of each peak were assigned to the populations of each co-conformation, and the scan-rate variation of each population was analyzed to obtain kinetic and thermodynamic data for the movement of the CBPQT4+ ring. The Gibbs free energy of activation at 298 K for the thermally activated movement was calculated to be 16.2 kcal mol(-1) for the rotaxane, and 16.7 and 19.2 kcal mol(-1) for the bipyridinium- and diazapyrenium-based bistable catenanes, respectively. These values differ from those obtained for the shuttling and circumrotational motions of degenerate rotaxanes and catenanes, respectively, indicating that the detailed chemical structure influences the rates of movement. In all cases, when the same bistable compounds were characterized in an electrolyte gel, the molecular mechanical motion slowed down significantly, concomitant with an increase in the activation barriers by more than 2 kcal mol(-1). Irrespective of the environment--solution, self-assembled monolayer or solid-state polymer gel--and of the molecular structure--rotaxane or catenane--a single and generic switching mechanism is observed for all bistable molecules.

Journal Article↗
PubMed1989

Possible functions of transmitter-controlled plateau potentials in alpha motoneurones.

An increasing number of vertebrate central neurones has been shown to possess complex membrane properties. However, the functional significance of such properties is unclear. The aim of the present paper is to review some old and new findings in this field from this laboratory. First, a bistability in alpha motoneurones in reduced preparations is described. Thereafter we present some new data on a bistable behaviour in motor units in unrestrained intact animals during posture. Finally, the possible role of motoneuronal bistability in locomotion and in spasticity is discussed. Recently a bistable firing behaviour in motoneurones was described in the unanaesthetized decerebrate cat. This behaviour is generated by a plateau potential, which causes long-lasting excitability increase and can be initiated and terminated by short-lasting synaptic excitation and inhibition respectively, and is contingent upon activity in descending noradrenergic and serotonergic systems. In an in vitro preparation of the turtle spinal cord the plateau potential was shown to be serotonin dependent and generated by a voltage-dependent non-inactivating calcium conductance. In order to elucidate possible functional consequences of a bistable firing behaviour in the intact animal, the firing pattern of individual soleus motor units was studied by means of chronic EMG registration in awake unrestrained rats during quiet standing. Implanted electrodes allowed the delivery of excitatory and inhibitory stimulus trains to the motoneurones. It was found that short-lasting synaptic stimulation could induce maintained shifts between two stable levels of motoneurone firing frequencies, as in the decerebrate cat. Spontaneous shifts between the same two levels were also present. It seems most likely that plateau potentials are responsible for this bistable firing property in intact animals. The role of plateau potentials in locomotion is difficult to study. At present there are no clear indications of the utilization of plateau potentials in locomotion in intact animals. However, "clamped frequency" bursts which are observed in fictive locomotion in spinal cats might be explained by plateaus. The existence of plateau potentials in motoneurones may also be of importance in spasticity. Therefore, the development of spasticity in two spinalized cats was followed for 3 weeks. Acute experiments demonstrated plateau potentials in some motoneurones in this preparation.

Action Potentials↗
PubMed2002

Neural correlates of spontaneous direction reversals in ambiguous apparent visual motion.

Looking at bistable visual stimuli, the observer experiences striking transitions between two competing percepts while the physical stimulus remains the same. Using functional imaging techniques, it is therefore possible to isolate neural correlates of perceptual changes that are independent of the low-level aspects of the stimulus. Previous experiments have demonstrated distributed activations in human extrastriate visual cortex related to switches between competing percepts. Here we asked where extrastriate responses still occur with a bistable stimulus that minimizes the cognitive difference between the two percepts. We used the "spinning wheel illusion," a bistable apparent motion stimulus of which both possible percepts correspond to the same object, share the same center, and are perceived as identically patterned stimuli moving at the same speed and changing only in direction. Using functional magnetic resonance imaging, we analyzed the spatial distribution of event-related activations occurring during spontaneous reversals of perceived direction of motion. In accordance with earlier neuroimaging findings for bistable percepts, we observed event-related activations in several frontal and parietal areas, including the superior parietal cortex bilaterally, the right inferior parietal cortex, and the premotor and inferior frontal cortex of both hemispheres. Furthermore, we found bilateral activations in the occipitotemporal junction (hMT+/V5) and in the lateral occipital sulcus ("KO") posterior to hMT+/V5, but not in areas of the "ventral stream" of cortical visual processing. Our data suggest that, while a frontoparietal network subserves more general aspects in bistable visual perception, the activations in functionally specialized extrastriate visual cortex are highly category- or attribute-specific.

Adult↗
PubMed2006

Oscillatory dynamics arising from competitive inhibition and multisite phosphorylation.

There have been a growing number of observations of oscillating protein levels (p53 and NFkB) in eukaryotic signalling pathways. This has resulted in a renewed interest in the mechanism by which such oscillations might occur. Recent computational work has shown that a multisite phosphorylation mechanism such as that found in the MAPK cascade can theoretically exhibit bistability. The bistable behavior was shown to arise from sequestration and saturation mechanisms for the enzymes that catalyse the multisite phosphorylation cycle. These effects generate the positive feedback necessary for bistability. In this paper we describe two kinds of oscillatory dynamics which can occur in a network by which, both use such bistable multisite phosphorylated cycles. In the first example, the fully phosphorylated form of the phosphorylated cycle represses the production of the kinase, which carries out the phosphorylation of the unphosphorylated states of the cycle. The dynamics of this system leads to a relaxation oscillator. In the second example, we consider a cascade of two cycles, in which the fully phosphorylated form of the kinase, in the first cycle, phosphorylates the unphosphorylated forms in the second cycle. A feedback loop, by which the fully phosphorylated form of the second cycle inhibits the kinase step in the first cycle is also present. In this case we obtain a ring oscillator. Both these networks illustrate the versatility of the multisite bistable network.

Animals↗
PubMed2001

Cue interactions, border ownership and illusory contours.

When two retinally adjacent image regions both claim 'ownership' of their common boundary based on different visual cues, their perceptual competition could result in: (1) cue averaging, in which the common boundary is not strongly perceived as owned by either region, or (2) perceptual bistability, in which the competing interpretations alternate in conscious perception over time. We report that when the perception of one or another illusory surface depends on the outcome of such a competition, the alternative percepts primarily exhibit bistability rather than averaging (or mutual weakening). More generally, we suggest that mutually inconsistent perceptual interpretations of sensory data will tend to exhibit bistability to the extent that they require significant constructive activity by vision. When one interpretation is more 'literal' (i.e. less constructive), it will tend to block alternative percepts. Put somewhat differently, when competing visual cues specify different preferred (but not necessary) interpretations, then the likely perceptual outcome is bistability rather than cue averaging. However, inconsistent visual cues can also result in perceptual bistability if the interpretations they specify are so incommensurable that simply averaging them would not provide useful information for perception.

Analysis of Variance↗
PubMed2004

Detection of multistability, bifurcations, and hysteresis in a large class of biological positive-feedback systems.

It is becoming increasingly clear that bistability (or, more generally, multistability) is an important recurring theme in cell signaling. Bistability may be of particular relevance to biological systems that switch between discrete states, generate oscillatory responses, or "remember" transitory stimuli. Standard mathematical methods allow the detection of bistability in some very simple feedback systems (systems with one or two proteins or genes that either activate each other or inhibit each other), but realistic depictions of signal transduction networks are invariably much more complex. Here, we show that for a class of feedback systems of arbitrary order the stability properties of the system can be deduced mathematically from how the system behaves when feedback is blocked. Provided that this open-loop, feedback-blocked system is monotone and possesses a sigmoidal characteristic, the system is guaranteed to be bistable for some range of feedback strengths. We present a simple graphical method for deducing the stability behavior and bifurcation diagrams for such systems and illustrate the method with two examples taken from recent experimental studies of bistable systems: a two-variable Cdc2/Wee1 system and a more complicated five-variable mitogen-activated protein kinase cascade.

CDC2 Protein Kinase↗
PubMed2006

Stochastic models for regulatory networks of the genetic toggle switch.

Bistability arises within a wide range of biological systems from the lambda phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. In this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks.

Models, Genetic↗