Decomposing the Local Arrow of Time in Interacting Systems.

We show that the evidence for a local arrow of time, which is equivalent to the entropy production in thermodynamic systems, can be decomposed. In a system with many degrees of freedom, there is a term that arises from the irreversible dynamics of the individual variables, and then a series of non-negative terms contributed by correlations among pairs, triplets, and higher-order combinations of variables. We illustrate this decomposition on simple models of noisy logical computations, and then apply it to the analysis of patterns of neural activity in the retina as it responds to complex dynamic visual scenes. We find that neural activity breaks detailed balance even when the visual inputs do not, and that this irreversibility arises primarily from interactions between pairs of neurons.

Motor control by precisely timed spike patterns.

A fundamental problem in neuroscience is understanding how sequences of action potentials ("spikes") encode information about sensory signals and motor outputs. Although traditional theories assume that this information is conveyed by the total number of spikes fired within a specified time interval (spike rate), recent studies have shown that additional information is carried by the millisecond-scale timing patterns of action potentials (spike timing). However, it is unknown whether or how subtle differences in spike timing drive differences in perception or behavior, leaving it unclear whether the information in spike timing actually plays a role in brain function. By examining the activity of individual motor units (the muscle fibers innervated by a single motor neuron) and manipulating patterns of activation of these neurons, we provide both correlative and causal evidence that the nervous system uses millisecond-scale variations in the timing of spikes within multispike patterns to control a vertebrate behavior-namely, respiration in the Bengalese finch, a songbird. These findings suggest that a fundamental assumption of current theories of motor coding requires revision.

Luria-Delbrück, revisited: the classic experiment does not rule out Lamarckian evolution.

We re-examined data from the classic Luria-Delbrück fluctuation experiment, which is often credited with establishing a Darwinian basis for evolution. We argue that, for the Lamarckian model of evolution to be ruled out by the experiment, the experiment must favor pure Darwinian evolution over both the Lamarckian model and a model that allows both Darwinian and Lamarckian mechanisms (as would happen for bacteria with CRISPR-Cas immunity). Analysis of the combined model was not performed in the original 1943 paper. The Luria-Delbrück paper also did not consider the possibility of neither model fitting the experiment. Using Bayesian model selection, we find that the Luria-Delbrück experiment, indeed, favors the Darwinian evolution over purely Lamarckian. However, our analysis does not rule out the combined model, and hence cannot rule out Lamarckian contributions to the evolutionary dynamics.

Emergent scale-free networks.

Many complex systems-from the Internet to social, biological, and communication networks-are thought to exhibit scale-free structure. However, prevailing explanations require that networks grow over time, an assumption that fails in some real-world settings. Here, we explain how scale-free structure can emerge without growth through network self-organization. Beginning with an arbitrary network, we allow connections to detach from random nodes and then reconnect under a mixture of preferential and random attachment. While the numbers of nodes and edges remain fixed, the degree distribution evolves toward a power-law with an exponent γ = 1 + 1 p that depends only on the proportion p of preferential (rather than random) attachment. Applying our model to several real networks, we infer p directly from data and predict the relationship between network size and degree heterogeneity. Together, these results establish how scale-free structure can arise in networks of constant size and density, with broad implications for the structure and function of complex systems.

Protocol for fluorescent live-cell staining of tardigrades.

Tardigrades are microscopic organisms with exceptional resilience to environmental extremes. Most protocols to visualize the internal anatomy of tardigrades rely on fixation, hampering our understanding of dynamic changes to organelles and other subcellular components. Here, we provide protocols for staining live tardigrade adults and other postembryonic stages, facilitating real-time visualization of structures including lipid droplets, mitochondria, lysosomes, and DNA.

Stimulus invariant aspects of the retinal code drive discriminability of natural scenes.

Everything that the brain sees must first be encoded by the retina, which maintains a reliable representation of the visual world in many different, complex natural scenes while also adapting to stimulus changes. Decomposing the population code into independent and cell-cell interactions reveals how broad scene structure is encoded in the adapted retinal output. By recording from the same retina while presenting many different natural movies, we see that the population structure, characterized by strong interactions, is consistent across both natural and synthetic stimuli. We show that these interactions contribute to encoding scene identity. We also demonstrate that this structure likely arises in part from shared bipolar cell input as well as from gap junctions between retinal ganglion cells and amacrine cells.

Emergence of local irreversibility in complex interacting systems.

Living systems are fundamentally irreversible, breaking detailed balance and establishing an arrow of time. But how does the evident arrow of time for a whole system arise from the interactions among its multiple elements? We show that the local evidence for the arrow of time, which is the entropy production for thermodynamic systems, can be decomposed. First, it can be split into two components: an independent term reflecting the dynamics of individual elements and an interaction term driven by the dependencies among elements. Adapting tools from nonequilibrium physics, we further decompose the interaction term into contributions from pairs of elements, triplets, and higher-order terms. We illustrate our methods on models of cellular sensing and logical computations, as well as on patterns of neural activity in the retina as it responds to visual inputs. We find that neural activity can define the arrow of time even when the visual inputs do not, and that the dominant contribution to this breaking of detailed balance comes from interactions among pairs of neurons.

A simple regulatory architecture allows learning the statistical structure of a changing environment.

Bacteria live in environments that are continuously fluctuating and changing. Exploiting any predictability of such fluctuations can lead to an increased fitness. On longer timescales, bacteria can 'learn' the structure of these fluctuations through evolution. However, on shorter timescales, inferring the statistics of the environment and acting upon this information would need to be accomplished by physiological mechanisms. Here, we use a model of metabolism to show that a simple generalization of a common regulatory motif (end-product inhibition) is sufficient both for learning continuous-valued features of the statistical structure of the environment and for translating this information into predictive behavior; moreover, it accomplishes these tasks near-optimally. We discuss plausible genetic circuits that could instantiate the mechanism we describe, including one similar to the architecture of two-component signaling, and argue that the key ingredients required for such predictive behavior are readily accessible to bacteria.

Associations inferred from previous experience can help an organism predict what might happen the next time it faces a similar situation. For example, it could anticipate the presence of certain resources based on a correlated environmental cue. The complex neural circuitry of the brain allows such associations to be learned and unlearned quickly, certainly within the lifetime of an animal. In contrast, the sub-cellular regulatory circuits of bacteria are only capable of very simple information processing. Thus, in bacteria, the 'learning' of environmental patterns is believed to mostly occur by evolutionary mechanisms, over many generations. Landmann et al. used computer simulations and a simple theoretical model to show that bacteria need not be limited by the slow speed of evolutionary trial and error. A basic regulatory circuit could, theoretically, allow a bacterium to learn subtle relationships between environmental factors within its lifetime. The essential components for this simulation can all be found in bacteria ­ including a large number of 'regulators', the molecules that control the rate of biochemical processes. And indeed, some organisms often have more of these biological actors than appears to be necessary. The results of Landmann et al. provide new hypothesis for how such seemingly 'superfluous' elements might actually be useful. Knowing that a learning process is theoretically possible, experimental biologists could now test if it appears in nature. Placing bacteria in more realistic, fluctuating conditions instead of a typical stable laboratory environment could demonstrate the role of the extra regulators in helping the microorganisms to adapt by 'learning'.

Estimation of mutual information for real-valued data with error bars and controlled bias.

Estimation of mutual information between (multidimensional) real-valued variables is used in analysis of complex systems, biological systems, and recently also quantum systems. This estimation is a hard problem, and universally good estimators provably do not exist. We focus on the estimator introduced by Kraskov et al. [Phys. Rev. E 69, 066138 (2004)PLEEE81539-375510.1103/PhysRevE.69.066138] based on the statistics of distances between neighboring data points, which empirically works for a wide class of underlying probability distributions. First, we illustrate pitfalls of naively applying bootstrapping to estimate the variance of the mutual information estimate. Then we improve this estimator by (1) expanding its range of applicability and by providing (2) a self-consistent way of verifying the absence of bias, (3) a method for estimation of its variance, and (4) guidelines for choosing the values of the free parameter of the estimator. We demonstrate the performance of our estimator on synthetic data sets, as well as on neurophysiological and systems biology data sets.