Realistic computational models of single neurons require component ion channels that reproduce experimental findings. Here, a topology-mutating genetic algorithm that searches for the best state diagram and transition-rate parameters to model macroscopic ion-channel behavior is described. Important features of the algorithm include a topology-altering strategy, automatic satisfaction of equilibrium constraints (microscopic reversibility), and multiple-protocol fitting using sequential goal programming rather than explicit weighting. Application of this genetic algorithm to design a sodium-channel model exhibiting both fast and prolonged inactivation yields a six-state model that produces realistic activity-dependent attenuation of action-potential backpropagation in current-clamp simulations of a CA1 pyramidal neuron.

A novel system for the generation and measurement of a two dimensional wind stimulus is proposed and described. This system was used to investigate the wind sensation of the American cockroach. The new aspects of this system are (a) a pair of computer driven wind tunnels that are shown to produce non-turbulent flows and (b) a novel fiber optic wind detector that measures both amplitude and direction of the wind. Winds can be produced and measured in behaviorally relevant frequency and amplitude ranges without perturbing the airflow. The combination of both the wind generation system and wind detector makes the system very flexible and allows the generation of stimuli with any given spectrum. The two dimensional wind stimulus is shown to be very reproducible. The wind detector is independent of the wind generation system so it can be used for measuring natural winds as well. Experimental data obtained on the cockroach are presented.

The vertebrate hindbrain contains various sensory-motor networks controlling movements of the eyes, jaw, head, and body. Here we show that stripes of neurons with shared neurotransmitter phenotype that extend throughout the hindbrain of young zebrafish reflect a broad underlying structural and functional patterning. The neurotransmitter stripes contain cell types with shared gross morphologies and transcription factor markers. Neurons within a stripe are stacked systematically by extent and location of axonal projections, input resistance, and age, and are recruited along the axis of the stripe during behavior. The implication of this pattern is that the many networks in hindbrain are constructed from a series of neuronal components organized into stripes that are ordered from top to bottom according to a neuron's age, structural and functional properties, and behavioral roles. This simple organization probably forms a foundation for the construction of the networks underlying the many behaviors produced by the hindbrain.

The vertebrate hindbrain contains various sensory-motor networks controlling movements of the eyes, jaw, head, and body. Here we show that stripes of neurons with shared neurotransmitter phenotype that extend throughout the hindbrain of young zebrafish reflect a broad underlying structural and functional patterning. The neurotransmitter stripes contain cell types with shared gross morphologies and transcription factor markers. Neurons within a stripe are stacked systematically by extent and location of axonal projections, input resistance, and age, and are recruited along the axis of the stripe during behavior. The implication of this pattern is that the many networks in hindbrain are constructed from a series of neuronal components organized into stripes that are ordered from top to bottom according to a neuron’s age, structural and functional properties, and behavioral roles. This simple organization probably forms a foundation for the construction of the networks underlying the many behaviors produced by the hindbrain.

Given a relatively short query stringW of lengthP, a long subject stringA of lengthN, and a thresholdD, theapproximate keyword search problem is to find all substrings ofA that align withW with not more than D insertions, deletions, and mismatches. In typical applications, such as searching a DNA sequence database, the size of the “database”A is much larger than that of the queryW, e.g.,N is on the order of millions or billions andP is a hundred to a thousand. In this paper we present an algorithm that given a precomputedindex of the databaseA, finds rare matches in time that issublinear inN, i.e.,N c for somec<1. The sequenceA must be overa. finite alphabet σ. More precisely, our algorithm requires 0(DN pow(ɛ)  logN) expected-time where ɛ=D/P is the maximum number of differences as a percentage of query length, and pow(ɛ) is an increasing and concave function that is 0 when ɛ=0. Thus the algorithm is superior to current O(DN) algorithms when ɛ is small enough to guarantee that pow(ɛ) < 1. As seen in the paper, this is true for a wide range of ɛ, e.g., ɛ. up to 33% for DNA sequences (¦⌆¦=4) and 56% for proteins sequences (¦⌆¦=20). In preliminary practical experiments, the approach gives a 50-to 500-fold improvement over previous algorithms for prolems of interest in molecular biology.

The gain of signaling in primary sensory circuits is matched to the stimulus intensity by the process of adaptation. Retinal neural circuits adapt to visual scene statistics, including the mean (background adaptation) and the temporal variance (contrast adaptation) of the light stimulus. The intrinsic properties of retinal bipolar cells and synapses contribute to background and contrast adaptation, but it is unclear whether both forms of adaptation depend on the same cellular mechanisms. Studies of bipolar cell synapses identified synaptic mechanisms of gain control, but the relevance of these mechanisms to visual processing is uncertain because of the historical focus on fast, phasic transmission rather than the tonic transmission evoked by ambient light. Here, we studied use-dependent regulation of bipolar cell synaptic transmission evoked by small, ongoing modulations of membrane potential (V(M)) in the physiological range. We made paired whole-cell recordings from rod bipolar (RB) and AII amacrine cells in a mouse retinal slice preparation. Quasi-white noise voltage commands modulated RB V(M) and evoked EPSCs in the AII. We mimicked changes in background luminance or contrast, respectively, by depolarizing the V(M) or increasing its variance. A linear systems analysis of synaptic transmission showed that increasing either the mean or the variance of the presynaptic V(M) reduced gain. Further electrophysiological and computational analyses demonstrated that adaptation to mean potential resulted from both Ca channel inactivation and vesicle depletion, whereas adaptation to variance resulted from vesicle depletion alone. Thus, background and contrast adaptation apparently depend in part on a common synaptic mechanism.

An important aspect of understanding a biological pathway is to delineate the transcriptional regulatory mechanisms of the genes involved. Two important tasks are often encountered when studying transcription regulation, i.e., (1) the identification of common transcriptional regulators of a set of coexpressed genes; (2) the identification of genes that are regulated by one or several transcription factors. In this study, a systematic and statistical approach was taken to accomplish these tasks by establishing an integrated model considering all of the promoters and characterized transcription factors (TFs) in the genome. A promoter analysis pipeline (PAP) was developed to implement this approach. PAP was tested using coregulated gene clusters collected from the literature. In most test cases, PAP identified the transcription regulators of the input genes accurately. When compared with chromatin immunoprecipitation experiment data, PAP’s predictions are consistent with the experimental observations. When PAP was used to analyze one published expression-profiling data set and two novel coregulated gene sets, PAP was able to generate biologically meaningful hypotheses. Therefore, by taking a systematic approach of considering all promoters and characterized TFs in our model, we were able to make more reliable predictions about the regulation of gene expression in mammalian organisms.

Flying insects are remarkable examples of sophisticated sensory-motor control systems. Insects have solved the fundamental challenge facing the field of mobile robots: robust sensory-motor mapping. Control models based on insects can contribute much to the design of robotic control systems. We present our work on a preliminary robotic control system inspired by current behavioural and physiological models of the fruit fly, Drosophila melanogaster. We designed a five-degrees-of-freedom robotic system that serves as a novel simulation/mobile robot hybrid. This design has allowed us to implement a fly-inspired control system that uses visual and mechanosensory feedback. Our results suggest that a simple control scheme can yield surprisingly robust fly-like robotic behaviour.

The gall-forming aphidCerataphis fransseni produces soldiers that defend against predators. Soldiers are produced soon after colony foundation and the number of soldiers increases nonlinearly during colony growth. The number of soldiers scales to the square-root of the number of non-soldiers and linearly to the surface area of the gall. This suggests that soldiers are produced to defend an area, for example the perimeter of the colony or the surface of the gall, rather than individual aphids.

Proteins that are essential for embryo production, cell division and early embryonic events are frequently reused later in embryogenesis, during organismal development or in the adult. Examining protein function across these different biological contexts requires tissue-specific perturbation. Here, we describe a method that uses expression of a fusion between a GFP-targeting nanobody and a SOCS-box containing ubiquitin ligase adaptor to target GFP-tagged proteins for degradation. When combined with endogenous locus GFP tagging by CRISPR-Cas9 or with rescue of a null mutant with a GFP fusion, this approach enables routine and efficient tissue-specific protein ablation. We show that this approach works in multiple tissues – the epidermis, intestine, body wall muscle, ciliated sensory neurons and touch receptor neurons – where it recapitulates expected loss-of-function mutant phenotypes. The transgene toolkit and the strain set described here will complement existing approaches to enable routine analysis of the tissue-specific roles of C. elegans proteins.