Stepwise molecular specification of excitatory synapse diversity onto cerebellar Purkinje cells.

Brain function relies on the generation of a large variety of morphologically and functionally diverse, but specific, neuronal synapses. Here we show that, in mice, the initial formation of synapses on cerebellar Purkinje cells involves a presynaptic protein-CBLN1, a member of the C1q protein family-that is secreted by all types of excitatory inputs. The molecular program then evolves only in one of the Purkinje cell inputs, the inferior olivary neurons, with the additional expression of the presynaptic secreted proteins C1QL1, CRTAC1 and LGI2.

Beta oscillations and waves in motor cortex can be accounted for by the interplay of spatially structured connectivity and fluctuating inputs.

The beta rhythm (13-30 Hz) is a prominent brain rhythm. Recordings in primates during instructed-delay reaching tasks have shown that different types of traveling waves of oscillatory activity are associated with episodes of beta oscillations in motor cortex during movement preparation. We propose here a simple model of motor cortex based on local excitatory-inhibitory neuronal populations coupled by long-range excitation, where additionally inputs to the motor cortex from other neural structures are represented by stochastic inputs on the different model populations.

Reciprocal stabilization of glycine receptors and gephyrin scaffold proteins at inhibitory synapses.

Postsynaptic scaffold proteins immobilize neurotransmitter receptors in the synaptic membrane opposite to presynaptic vesicle release sites, thus ensuring efficient synaptic transmission. At inhibitory synapses in the spinal cord, the main scaffold protein gephyrin assembles in dense molecule clusters that provide binding sites for glycine receptors (GlyRs). Gephyrin and GlyRs can also interact outside of synapses, where they form receptor-scaffold complexes.

Synchronization, Stochasticity, and Phase Waves in Neuronal Networks With Spatially-Structured Connectivity.

Oscillations in the beta/low gamma range (10-45 Hz) are recorded in diverse neural structures. They have successfully been modeled as sparsely synchronized oscillations arising from reciprocal interactions between randomly connected excitatory (E) pyramidal cells and local interneurons (I). The synchronization of spatially distant oscillatory spiking E-I modules has been well-studied in the rate model framework but less so for modules of spiking neurons.

Lifetime of a structure evolving by cluster aggregation and particle loss, and application to postsynaptic scaffold domains.

The dynamics of several mesoscopic biological structures depend on the interplay of growth through the incorporation of components of different sizes laterally diffusing along the cell membrane, and loss by component turnover. In particular, a model of such an out-of-equilibrium dynamics has recently been proposed for postsynaptic scaffold domains, which are key structures of neuronal synapses. It is of interest to estimate the lifetime of these mesoscopic structures, especially in the context of synapses where this time is related to memory retention.

Cerebellar learning using perturbations.

The cerebellum aids the learning of fast, coordinated movements. According to current consensus, erroneously active parallel fibre synapses are depressed by complex spikes signalling movement errors. However, this theory cannot solve the of processing a global movement evaluation into multiple cell-specific error signals.

An aggregation-removal model for the formation and size determination of post-synaptic scaffold domains.

The formation and stability of synapses are key questions in neuroscience. Post-synaptic domains have been classically conceived as resulting from local insertion and turnover of proteins at the synapse. However, insertion is likely to occur outside the post-synaptic domains and advances in single-molecule imaging have shown that proteins diffuse in the plane of the membrane prior to their accumulation at synapses.

Collective cell migration: a physics perspective.

Cells have traditionally been viewed either as independently moving entities or as somewhat static parts of tissues. However, it is now clear that in many cases, multiple cells coordinate their motions and move as collective entities. Well-studied examples comprise development events, as well as physiological and pathological situations.

The effects of proteasomal inhibition on synaptic proteostasis.

Synaptic function crucially depends on uninterrupted synthesis and degradation of synaptic proteins. While much has been learned on synaptic protein synthesis, little is known on the routes by which synaptic proteins are degraded. Here we systematically studied how inhibition of the ubiquitin-proteasome system (UPS) affects the degradation rates of thousands of neuronal and synaptic proteins.

Sustained Rhythmic Brain Activity Underlies Visual Motion Perception in Zebrafish.

Following moving visual stimuli (conditioning stimuli, CS), many organisms perceive, in the absence of physical stimuli, illusory motion in the opposite direction. This phenomenon is known as the motion aftereffect (MAE). Here, we use MAE as a tool to study the neuronal basis of visual motion perception in zebrafish larvae.

MyoD reprogramming requires Six1 and Six4 homeoproteins: genome-wide cis-regulatory module analysis.

Myogenic regulatory factors of the MyoD family have the ability to reprogram differentiated cells toward a myogenic fate. In this study, we demonstrate that Six1 or Six4 are required for the reprogramming by MyoD of mouse embryonic fibroblasts (MEFs). Using microarray experiments, we found 761 genes under the control of both Six and MyoD.

Time-invariant feed-forward inhibition of Purkinje cells in the cerebellar cortex in vivo.

Key Points: We performed extracellular recording of pairs of interneuron-Purkinje cells in vivo. A single interneuron produces a substantial, short-lasting, inhibition of Purkinje cells. Feed-forward inhibition is associated with characteristic asymmetric cross-correlograms.

Modeling the finger instability in an expanding cell monolayer.

Collective motion occurs in many biological processes, such as wound healing, tumor invasion and embryogenesis. Experiments of cell monolayer migration have revealed the spontaneous formation of finger-like instabilities, with leader cells at their tips. We present a particle-based model for collective cell migration, based on several elements that have been found experimentally to influence cellular movement.

Neuronal morphology generates high-frequency firing resonance.

The attenuation of neuronal voltage responses to high-frequency current inputs by the membrane capacitance is believed to limit single-cell bandwidth. However, neuronal populations subject to stochastic fluctuations can follow inputs beyond this limit. We investigated this apparent paradox theoretically and experimentally using Purkinje cells in the cerebellum, a motor structure that benefits from rapid information transfer.

Ceramic liner fracture and impingement in total hip arthroplasty.

Background: Ceramic-on-ceramic bearing surfaces were developed to provide an alternate to metal-on-polyethylene to decrease wear-induced osteolysis in total hip arthroplasty patients. In an effort to decrease the risk of ceramic acetabular component fracture or damage during implantation, a raised metal rim was added.

Questions/purposes: How many fractures or impingements have occurred in our population of patients with ceramic liners with raised rims?

Methods: With IRB-approved consent, a case series was reviewed from a single center registry and 4 of 169 patients were identified who had revision hip surgery with the ceramic liner with a raised metal rim: one for ceramic liner fracture and three for metallosis, pain, and squeaking.

A general pairwise interaction model provides an accurate description of in vivo transcription factor binding sites.

The identification of transcription factor binding sites (TFBSs) on genomic DNA is of crucial importance for understanding and predicting regulatory elements in gene networks. TFBS motifs are commonly described by Position Weight Matrices (PWMs), in which each DNA base pair contributes independently to the transcription factor (TF) binding. However, this description ignores correlations between nucleotides at different positions, and is generally inaccurate: analysing fly and mouse in vivo ChIPseq data, we show that in most cases the PWM model fails to reproduce the observed statistics of TFBSs.

Six homeoproteins and a Iinc-RNA at the fast MYH locus lock fast myofiber terminal phenotype.

Thousands of long intergenic non-coding RNAs (lincRNAs) are encoded by the mammalian genome. However, the function of most of these lincRNAs has not been identified in vivo. Here, we demonstrate a role for a novel lincRNA, linc-MYH, in adult fast-type myofiber specialization.

Emergence of collective modes and tri-dimensional structures from epithelial confinement.

Many in vivo processes, including morphogenesis or tumour maturation, involve small populations of cells within a spatially restricted region. However, the basic mechanisms underlying the dynamics of confined cell assemblies remain largely to be deciphered and would greatly benefit from well-controlled in vitro experiments. Here we show that confluent epithelial cells cultured on finite population-sized domains, exhibit collective low-frequency radial displacement modes as well as stochastic global rotation reversals.

Imogene: identification of motifs and cis-regulatory modules underlying gene co-regulation.

Cis-regulatory modules (CRMs) and motifs play a central role in tissue and condition-specific gene expression. Here we present Imogene, an ensemble of statistical tools that we have developed to facilitate their identification and implemented in a publicly available software. Starting from a small training set of mammalian or fly CRMs that drive similar gene expression profiles, Imogene determines de novo cis-regulatory motifs that underlie this co-expression.

Single neuron dynamics and computation.

At the single neuron level, information processing involves the transformation of input spike trains into an appropriate output spike train. Building upon the classical view of a neuron as a threshold device, models have been developed in recent years that take into account the diverse electrophysiological make-up of neurons and accurately describe their input-output relations. Here, we review these recent advances and survey the computational roles that they have uncovered for various electrophysiological properties, for dendritic arbor anatomy as well as for short-term synaptic plasticity.

Genome-wide analyses of Shavenbaby target genes reveals distinct features of enhancer organization.

Background: Developmental programs are implemented by regulatory interactions between Transcription Factors (TFs) and their target genes, which remain poorly understood. While recent studies have focused on regulatory cascades of TFs that govern early development, little is known about how the ultimate effectors of cell differentiation are selected and controlled. We addressed this question during late Drosophila embryogenesis, when the finely tuned expression of the TF Ovo/Shavenbaby (Svb) triggers the morphological differentiation of epidermal trichomes.

Collective cell motion in an epithelial sheet can be quantitatively described by a stochastic interacting particle model.

Modelling the displacement of thousands of cells that move in a collective way is required for the simulation and the theoretical analysis of various biological processes. Here, we tackle this question in the controlled setting where the motion of Madin-Darby Canine Kidney (MDCK) cells in a confluent epithelium is triggered by the unmasking of free surface. We develop a simple model in which cells are described as point particles with a dynamic based on the two premises that, first, cells move in a stochastic manner and, second, tend to adapt their motion to that of their neighbors.

Different cell fates from cell-cell interactions: core architectures of two-cell bistable networks.

The acquisition of different fates by cells that are initially in the same state is central to development. Here, we investigate the possible structures of bistable genetic networks that can allow two identical cells to acquire different fates through cell-cell interactions. Cell-autonomous bistable networks have been previously sampled using an evolutionary algorithm.