A compact statistical model of the song syntax in Bengalese finch

Songs of many songbird species consist of variable sequences of a finite number of syllables. A common approach for characterizing the syntax of these complex syllable sequences is to use transition probabilities between the syllables. This is equivalent to the Markov model, in which each syllable is associated with one state, and the transition probabilities between the states do not depend on the state transition history. Here we analyze the song syntax in a Bengalese finch. We show that the Markov model fails to capture the statistical properties of the syllable sequences. Instead, a state transition model that accurately describes the statistics of the syllable sequences includes adaptation of the self-transition probabilities when states are repeatedly revisited, and allows associations of more than one state to the same syllable. Such a model does not increase the model complexity significantly. Mathematically, the model is a partially observable Markov model with adaptation (POMMA). The success of the POMMA supports the branching chain network hypothesis of how syntax is controlled within the premotor song nucleus HVC, and suggests that adaptation and many-to-one mapping from neural substrates to syllables are important features of the neural control of complex song syntax

Responses of Tectal Neurons to Contrasting Stimuli: An Electrophysiological Study in the Barn Owl

The saliency of visual objects is based on the center to background contrast. Particularly objects differing in one feature from the background may be perceived as more salient. It is not clear to what extent this so called “pop-out” effect observed in humans and primates governs saliency perception in non-primates as well. In this study we searched for neural-correlates of pop-out perception in neurons located in the optic tectum of the barn owl. We measured the responses of tectal neurons to stimuli appearing within the visual receptive field, embedded in a large array of additional stimuli (the background). Responses were compared between contrasting and uniform conditions. In a contrasting condition the center was different from the background while in the uniform condition it was identical to the background. Most tectal neurons responded better to stimuli in the contrsating condition compared to the uniform condition when the contrast between center and background was the direction of motion but not when it was the orientation of a bar. Tectal neurons also preferred contrasting over uniform stimuli when the center was looming and the background receding but not when the center was receding and the background looming. Therefore, our results do not support the hypothesis that tectal neurons are sensitive to pop-out per-se. The specific sensitivity to the motion contrasting stimulus is consistent with the idea that object motion and not large field motion (e.g., self-induced motion) is coded in the neural responses of tectal neurons

Masking of Figure-Ground Texture and Single Targets by Surround Inhibition: A Computational Spiking Model

A visual stimulus can be made invisible, i.e. masked, by the presentation of a second stimulus. In the sensory cortex, neural responses to a masked stimulus are suppressed, yet how this suppression comes about is still debated. Inhibitory models explain masking by asserting that the mask exerts an inhibitory influence on the responses of a neuron evoked by the target. However, other models argue that the masking interferes with recurrent or reentrant processing. Using computer modeling, we show that surround inhibition evoked by ON and OFF responses to the mask suppresses the responses to a briefly presented stimulus in forward and backward masking paradigms. Our model results resemble several previously described psychophysical and neurophysiological findings in perceptual masking experiments and are in line with earlier theoretical descriptions of masking. We suggest that precise spatiotemporal influence of surround inhibition is relevant for visual detection

The pathophysiology of restricted repetitive behavior

Restricted, repetitive behaviors (RRBs) are heterogeneous ranging from stereotypic body movements to rituals to restricted interests. RRBs are most strongly associated with autism but occur in a number of other clinical disorders as well as in typical development. There does not seem to be a category of RRB that is unique or specific to autism and RRB does not seem to be robustly correlated with specific cognitive, sensory or motor abnormalities in autism. Despite its clinical significance, little is known about the pathophysiology of RRB. Both clinical and animal models studies link repetitive behaviors to genetic mutations and a number of specific genetic syndromes have RRBs as part of the clinical phenotype. Genetic risk factors may interact with experiential factors resulting in the extremes in repetitive behavior phenotypic expression that characterize autism. Few studies of individuals with autism have correlated MRI findings and RRBs and no attempt has been made to associate RRB and post-mortem tissue findings. Available clinical and animal models data indicate functional and structural alterations in cortical-basal ganglia circuitry in the expression of RRB, however. Our own studies point to reduced activity of the indirect basal ganglia pathway being associated with high levels of repetitive behavior in an animal model. These findings, if generalizable, suggest specific therapeutic targets. These, and perhaps other, perturbations to cortical basal ganglia circuitry are mediated by specific molecular mechanisms (e.g., altered gene expression) that result in long-term, experience-dependent neuroadaptations that initiate and maintain repetitive behavior. A great deal more research is needed to uncover such mechanisms. Work in areas such as substance abuse, OCD, Tourette syndrome, Parkinson’s disease, and dementias promise to provide findings critical for identifying neurobiological mechanisms relevant to RRB in autism. Moreover, basic research in areas such as birdsong, habit formation, and procedural learning may provide additional, much needed clues. Understanding the pathophysioloy of repetitive behavior will be critical to identifying novel therapeutic targets and strategies for individuals with autism

Cardiac cell modelling: observations from the heart of the cardiac physiome project

In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field

Rapid diffusion of green fluorescent protein in the mitochondrial matrix.

It is thought that the high protein density in the mitochondrial matrix results in severely restricted solute diffusion and metabolite channeling from one enzyme to another without free aqueous-phase diffusion. To test this hypothesis, we measured the diffusion of green fluorescent protein (GFP) expressed in the mitochondrial matrix of fibroblast, liver, skeletal muscle, and epithelial cell lines. Spot photobleaching of GFP with a 100x objective (0.8-micron spot diam) gave half-times for fluorescence recovery of 15-19 ms with >90% of the GFP mobile. As predicted for aqueous-phase diffusion in a confined compartment, fluorescence recovery was slowed or abolished by increased laser spot size or bleach time, and by paraformaldehyde fixation. Quantitative analysis of bleach data using a mathematical model of matrix diffusion gave GFP diffusion coefficients of 2-3 x 10(-7) cm2/s, only three to fourfold less than that for GFP diffusion in water. In contrast, little recovery was found for bleaching of GFP in fusion with subunits of the fatty acid beta-oxidation multienzyme complex that are normally present in the matrix. Measurement of the rotation of unconjugated GFP by time-resolved anisotropy gave a rotational correlation time of 23.3 +/- 1 ns, similar to that of 20 ns for GFP rotation in water. A rapid rotational correlation time of 325 ps was also found for a small fluorescent probe (BCECF, approximately 0.5 kD) in the matrix of isolated liver mitochondria. The rapid and unrestricted diffusion of solutes in the mitochondrial matrix suggests that metabolite channeling may not be required to overcome diffusive barriers. We propose that the clustering of matrix enzymes in membrane-associated complexes might serve to establish a relatively uncrowded aqueous space in which solutes can freely diffuse