Cellular geometry and epithelial-mesenchymal plasticity intersect with PIEZO1 in breast cancer cells.

Differences in shape can be a distinguishing feature between different cell types, but the shape of a cell can also be dynamic. Changes in cell shape are critical when cancer cells escape from the primary tumor and undergo major morphological changes that allow them to squeeze between endothelial cells, enter the vasculature, and metastasize to other areas of the body. A shift from rounded to spindly cellular geometry is a consequence of epithelial-mesenchymal plasticity, which is also associated with changes in gene expression, increased invasiveness, and therapeutic resistance.

Cortical activity emerges in region-specific patterns during early brain development.

The development of precise neural circuits in the brain requires spontaneous patterns of neural activity prior to functional maturation. In the rodent cerebral cortex, patchwork and wave patterns of activity develop in somatosensory and visual regions, respectively, and are present at birth. However, whether such activity patterns occur in noneutherian mammals, as well as when and how they arise during development, remain open questions relevant for understanding brain formation in health and disease.

Whole-brain imaging of freely-moving zebrafish.

One of the holy grails of neuroscience is to record the activity of every neuron in the brain while an animal moves freely and performs complex behavioral tasks. While important steps forward have been taken recently in large-scale neural recording in rodent models, single neuron resolution across the entire mammalian brain remains elusive. In contrast the larval zebrafish offers great promise in this regard.

Cortical activity emerges in region-specific patterns during early brain development.

Unlabelled: The development of precise neural circuits in the brain requires spontaneous patterns of neural activity prior to functional maturation. In the rodent cerebral cortex patchwork and wave patterns of activity develop in somatosensory and visual regions, respectively, and are present at birth. However, whether such activity patterns occur in non-eutherian mammals, as well as when and how they arise during development remain open questions relevant to understand brain formation in health and disease.

From perception to behavior: The neural circuits underlying prey hunting in larval zebrafish.

A key challenge for neural systems is to extract relevant information from the environment and make appropriate behavioral responses. The larval zebrafish offers an exciting opportunity for studying these sensing processes and sensory-motor transformations. Prey hunting is an instinctual behavior of zebrafish that requires the brain to extract and combine different attributes of the sensory input and form appropriate motor outputs.

Mutation Alters the Early Development of Sensory Coding and Hunting and Social Behaviors in Larval Zebrafish.

Autism spectrum disorders (ASDs) are developmental in origin; however, little is known about how they affect the early development of behavior and sensory coding. The most common inherited form of autism is Fragile X syndrome (FXS), caused by a mutation in Mutation of in zebrafish causes anxiety-like behavior, hyperactivity, and hypersensitivity in auditory and visual processing. Here, we show that zebrafish -/- mutant larvae of either sex also display changes in hunting behavior, tectal coding, and social interaction.

Inference of Multiplicative Factors Underlying Neural Variability in Calcium Imaging Data.

Understanding brain function requires disentangling the high-dimensional activity of populations of neurons. Calcium imaging is an increasingly popular technique for monitoring such neural activity, but computational tools for interpreting extracted calcium signals are lacking. While there has been a substantial development of factor analysis-type methods for neural spike train analysis, similar methods targeted at calcium imaging data are only beginning to emerge.

Unsupervised quantification of naturalistic animal behaviors for gaining insight into the brain.

Neural computation has evolved to optimize the behaviors that enable our survival. Although much previous work in neuroscience has focused on constrained task behaviors, recent advances in computer vision are fueling a trend toward the study of naturalistic behaviors. Automated tracking of fine-scale behaviors is generating rich datasets for animal models including rodents, fruit flies, zebrafish, and worms.

Zebrafish Chromosome 14 Gene Differential Expression in the Model of Fragile X Syndrome.

Zebrafish represent a valuable model for investigating the molecular and cellular basis of Fragile X syndrome (FXS). Reduced expression of the zebrafish orthologous gene, , causes developmental and behavioural phenotypes related to FXS. Zebrafish homozygous for the hu2787 non-sense mutation allele of are widely used to model FXS, although FXS-relevant phenotypes seen from morpholino antisense oligonucleotide (morpholino) suppression of transcript translation were not observed when hu2787 was first described.

Spontaneous and evoked activity patterns diverge over development.

The immature brain is highly spontaneously active. Over development this activity must be integrated with emerging patterns of stimulus-evoked activity, but little is known about how this occurs. Here we investigated this question by recording spontaneous and evoked neural activity in the larval zebrafish tectum from 4 to 15 days post-fertilisation.

Limitations to Estimating Mutual Information in Large Neural Populations.

Information theory provides a powerful framework to analyse the representation of sensory stimuli in neural population activity. However, estimating the quantities involved such as entropy and mutual information from finite samples is notoriously hard and any direct estimate is known to be heavily biased. This is especially true when considering large neural populations.

Model-based decoupling of evoked and spontaneous neural activity in calcium imaging data.

The pattern of neural activity evoked by a stimulus can be substantially affected by ongoing spontaneous activity. Separating these two types of activity is particularly important for calcium imaging data given the slow temporal dynamics of calcium indicators. Here we present a statistical model that decouples stimulus-driven activity from low dimensional spontaneous activity in this case.

Modular transient nanoclustering of activated β2-adrenergic receptors revealed by single-molecule tracking of conformation-specific nanobodies.

None of the current superresolution microscopy techniques can reliably image the changes in endogenous protein nanoclustering dynamics associated with specific conformations in live cells. Single-domain nanobodies have been invaluable tools to isolate defined conformational states of proteins, and we reasoned that expressing these nanobodies coupled to single-molecule imaging-amenable tags could allow superresolution analysis of endogenous proteins in discrete conformational states. Here, we used anti-GFP nanobodies tagged with photoconvertible mEos expressed as intrabodies, as a proof-of-concept to perform single-particle tracking on a range of GFP proteins expressed in live cells, neurons, and small organisms.

Altered brain-wide auditory networks in a zebrafish model of fragile X syndrome.

Background: Loss or disrupted expression of the FMR1 gene causes fragile X syndrome (FXS), the most common monogenetic form of autism in humans. Although disruptions in sensory processing are core traits of FXS and autism, the neural underpinnings of these phenotypes are poorly understood. Using calcium imaging to record from the entire brain at cellular resolution, we investigated neuronal responses to visual and auditory stimuli in larval zebrafish, using fmr1 mutants to model FXS.

Behavioral Signatures of a Developing Neural Code.

During early life, neural codes must develop to appropriately transform sensory inputs into behavioral outputs. Here, we demonstrate a link between the maturity of neural coding in the visual brain and developmental changes in visually guided behavior. In zebrafish larvae, we show that visually driven hunting behavior improves from 4 to 15 days post-fertilization, becoming faster and more accurate.

Correction to: Detecting neural assemblies in calcium imaging data.

Upon publication of the original article, [1], the authors noticed that the first authors' affiliation contained an error.

Probabilistic Encoding Models for Multivariate Neural Data.

A key problem in systems neuroscience is to characterize how populations of neurons encode information in their patterns of activity. An understanding of the encoding process is essential both for gaining insight into the origins of perception and for the development of brain-computer interfaces. However, this characterization is complicated by the highly variable nature of neural responses, and thus usually requires probabilistic methods for analysis.

Detecting neural assemblies in calcium imaging data.

Background: Activity in populations of neurons often takes the form of assemblies, where specific groups of neurons tend to activate at the same time. However, in calcium imaging data, reliably identifying these assemblies is a challenging problem, and the relative performance of different assembly-detection algorithms is unknown.

Results: To test the performance of several recently proposed assembly-detection algorithms, we first generated large surrogate datasets of calcium imaging data with predefined assembly structures and characterised the ability of the algorithms to recover known assemblies.

Theoretical Models of Neural Development.

Constructing a functioning nervous system requires the precise orchestration of a vast array of mechanical, molecular, and neural-activity-dependent cues. Theoretical models can play a vital role in helping to frame quantitative issues, reveal mathematical commonalities between apparently diverse systems, identify what is and what is not possible in principle, and test the abilities of specific mechanisms to explain the data. This review focuses on the progress that has been made over the last decade in our theoretical understanding of neural development.

Emergence of spontaneous assembly activity in developing neural networks without afferent input.

Spontaneous activity is a fundamental characteristic of the developing nervous system. Intriguingly, it often takes the form of multiple structured assemblies of neurons. Such assemblies can form even in the absence of afferent input, for instance in the zebrafish optic tectum after bilateral enucleation early in life.

Chemotactic responses of growing neurites to precisely controlled gradients of nerve growth factor.

Chemotaxis plays a key role in many biological systems. In particular in the context of the developing nervous system, growing neurites can respond in vitro to shallow gradients of chemotropic molecules such as nerve growth factor (NGF). However, in such studies the gradient parameters are often not well controlled.

Principles of Functional Circuit Connectivity: Insights From Spontaneous Activity in the Zebrafish Optic Tectum.

The brain is continuously active, even in the absence of external stimulation. In the optic tectum of the zebrafish larva, this spontaneous activity is spatially organized and reflects the circuit's functional connectivity. The structure of the spontaneous activity displayed patterns associated with aspects of the larva's preferences when engaging in complex visuo-motor behaviors, suggesting that the tectal circuit is adapted for the circuit's functional role in detecting visual cues and generating adequate motor behaviors.

Code Under Construction: Neural Coding Over Development.

Developing animals must begin to interact with the world before their neural development is complete. This means they must build neural codes appropriate for turning sensory inputs into motor outputs adaptively as their neural hardware matures. We review some recent progress in the understanding of the relationship between neural coding and neural circuit development.