GABA-Induced Seizure-Like Events Caused by Multi-ionic Interactive Dynamics.

Experimental evidence showed that an increase in intracellular chloride concentration [Formula: see text] caused by gamma-aminobutyric acid (GABA) input can promote epileptic firing activity, but the actual mechanisms remain elusive. Here in this theoretical work, we show that influx of chloride and concomitant bicarbonate ion [Formula: see text] efflux upon GABA receptor activation can induce epileptic firing activity by transition of GABA from inhibition to excitation. We analyzed the intrinsic property of neuron firing states as a function of [Formula: see text] We found that as [Formula: see text] increases, the system exhibits a saddle-node bifurcation, above which the neuron exhibits a spectrum of intensive firing, periodic bursting interrupted by depolarization block (DB) state, and eventually a stable DB through a Hopf bifurcation.

Branch-specific clustered parallel fiber input controls dendritic computation in Purkinje cells.

Most central neurons have intricately branched dendritic trees that integrate massive numbers of synaptic inputs. Intrinsic active mechanisms in dendrites can be heterogeneous and be modulated in a branch-specific way. However, it remains poorly understood how heterogeneous intrinsic properties contribute to processing of synaptic input.

Vesicle and reaction-diffusion hybrid modeling with STEPS.

Vesicles carry out many essential functions within cells through the processes of endocytosis, exocytosis, and passive and active transport. This includes transporting and delivering molecules between different parts of the cell, and storing and releasing neurotransmitters in neurons. To date, computational simulation of these key biological players has been rather limited and has not advanced at the same pace as other aspects of cell modeling, restricting the realism of computational models.

Prenatal phenotype of a homozygous nonsense MPDZ variant in a fetus with severe congenital hydrocephalus.

The fetal phenotype of MPDZ-associated congenital hydrocephalus type 2 with or without brain or eye anomalies (HYC2) (OMIM 615219) is not well described in the literature. The present case shows not previously published clinical fetal features that are detected during routine second trimester ultrasound screening at 21 weeks of gestation such as bilateral ventriculomegaly, lean cavum septum pellucidum, suspicion of hypoplastic corpus callosum, and suspicion of gyration disorder with normal fossa posterior. Combination of clinical features and a gene panel for congenital malformation syndromes detected a homozygous, likely pathogenic nonsense variant in the MPDZ gene.

Recent data on the cerebellum require new models and theories.

The cerebellum has been a popular topic for theoretical studies because its structure was thought to be simple. Since David Marr and James Albus related its function to motor skill learning and proposed the Marr-Albus cerebellar learning model, this theory has guided and inspired cerebellar research. In this review, we summarize the theoretical progress that has been made within this framework of error-based supervised learning.

Efficient simulation of neural development using shared memory parallelization.

Unlabelled: The Neural Development Simulator, NeuroDevSim, is a Python module that simulates the most important aspects of brain development: morphological growth, migration, and pruning. It uses an agent-based modeling approach inherited from the NeuroMaC software. Each cycle has agents called fronts execute model-specific code.

Models of Purkinje cell dendritic tree selection during early cerebellar development.

We investigate the relationship between primary dendrite selection of Purkinje cells and migration of their presynaptic partner granule cells during early cerebellar development. During postnatal development, each Purkinje cell grows more than three dendritic trees, from which a primary tree is selected for development, whereas the others completely retract. Experimental studies suggest that this selection process is coordinated by physical and synaptic interactions with granule cells, which undergo a massive migration at the same time.

Multidimensional cerebellar computations for flexible kinematic control of movements.

Both the environment and our body keep changing dynamically. Hence, ensuring movement precision requires adaptation to multiple demands occurring simultaneously. Here we show that the cerebellum performs the necessary multi-dimensional computations for the flexible control of different movement parameters depending on the prevailing context.

STEPS 4.0: Fast and memory-efficient molecular simulations of neurons at the nanoscale.

Recent advances in computational neuroscience have demonstrated the usefulness and importance of stochastic, spatial reaction-diffusion simulations. However, ever increasing model complexity renders traditional serial solvers, as well as naive parallel implementations, inadequate. This paper introduces a new generation of the STochastic Engine for Pathway Simulation (STEPS) project (http://steps.

Self-configuring feedback loops for sensorimotor control.

How dynamic interactions between nervous system regions in mammals performs online motor control remains an unsolved problem. In this paper, we show that feedback control is a simple, yet powerful way to understand the neural dynamics of sensorimotor control. We make our case using a minimal model comprising spinal cord, sensory and motor cortex, coupled by long connections that are plastic.

Control of Ca signals by astrocyte nanoscale morphology at tripartite synapses.

Much of the Ca activity in astrocytes is spatially restricted to microdomains and occurs in fine processes that form a complex anatomical meshwork, the so-called spongiform domain. A growing body of literature indicates that those astrocytic Ca signals can influence the activity of neuronal synapses and thus tune the flow of information through neuronal circuits. Because of technical difficulties in accessing the small spatial scale involved, the role of astrocyte morphology on Ca microdomain activity remains poorly understood.

Modeling Neurons in 3D at the Nanoscale.

For decades, neurons have been modeled by methods developed by early pioneers in the field such as Rall, Hodgkin and Huxley, as cable-like morphological structures with voltage changes that are governed by a series of ordinary differential equations describing the conductances of ion channels embedded in the membrane. In recent years, advances in experimental techniques have improved our knowledge of the morphological and molecular makeup of neurons, and this has come alongside ever-increasing computational power and the wider availability of computer hardware to researchers. This has opened up the possibility of more detailed 3D modeling of neuronal morphologies and their molecular makeup, a new, emerging component of the field of computational neuroscience that is expected to play an important role in building our understanding of neurons and their behavior into the future.

A differential Hebbian framework for biologically-plausible motor control.

In this paper we explore a neural control architecture that is both biologically plausible, and capable of fully autonomous learning. It consists of feedback controllers that learn to achieve a desired state by selecting the errors that should drive them. This selection happens through a family of differential Hebbian learning rules that, through interaction with the environment, can learn to control systems where the error responds monotonically to the control signal.

Plasma membrane perforation by GSDME during apoptosis-driven secondary necrosis.

Secondary necrosis has long been perceived as an uncontrolled process resulting in total lysis of the apoptotic cell. Recently, it was shown that progression of apoptosis to secondary necrosis is regulated by Gasdermin E (GSDME), which requires activation by caspase-3. Although the contribution of GSDME in this context has been attributed to its pore-forming capacity, little is known about the kinetics and size characteristics of this.

Punching Holes in Cellular Membranes: Biology and Evolution of Gasdermins.

The gasdermin (GSDM) family has evolved as six gene clusters (GSDMA-E and Pejvakin, PJVK), and GSDM proteins are characterized by a unique N-terminal domain (N-GSDM). With the exception of PJVK, the N-GSDM domain is capable of executing plasma membrane permeabilization. Depending on the cell death modality, several protease- and kinase-dependent mechanisms directly regulate the activity of GSDME and GSDMD, the two most widely expressed and best-studied GSDMs.

The Cellular Electrophysiological Properties Underlying Multiplexed Coding in Purkinje Cells.

Neuronal firing patterns are crucial to underpin circuit level behaviors. In cerebellar Purkinje cells (PCs), both spike rates and pauses are used for behavioral coding, but the cellular mechanisms causing code transitions remain unknown. We use a well-validated PC model to explore the coding strategy that individual PCs use to process parallel fiber (PF) inputs.

GSDME: A Potential Ally in Cancer Detection and Treatment.

Gasdermin E (GSDME) is an executioner of caspase-3 mediated regulated pyroptosis, and as such plays an important role in several cancers. Recent findings highlighted the potential of GSDME as a biomarker that can be implemented in cancer diagnosis, monitoring, and therapy.

GSDME and its role in cancer: From behind the scenes to the front of the stage.

Gasdermin E (GSDME), a gene originally involved in hereditary hearing loss, has been associated with several types of cancer in the last two decades. Recently, GSDME was identified as a pore-forming molecule, which is activated following caspase-3-mediated cleavage resulting in so-called secondary necrosis following apoptotic cell death, or in primary necrotic cell death without an apoptotic phase, so-called pyroptosis-like. This implication in cell death execution suggests its potential role as a tumor suppressor.

Firing rate-dependent phase responses of Purkinje cells support transient oscillations.

Both spike rate and timing can transmit information in the brain. Phase response curves (PRCs) quantify how a neuron transforms input to output by spike timing. PRCs exhibit strong firing-rate adaptation, but its mechanism and relevance for network output are poorly understood.

Pycabnn: Efficient and Extensible Software to Construct an Anatomical Basis for a Physiologically Realistic Neural Network Model.

Physiologically detailed models of neural networks are an important tool for studying how biophysical mechanisms impact neural information processing. An important, fundamental step in constructing such a model is determining where neurons are placed and how they connect to each other, based on known anatomical properties and constraints given by experimental data. Here we present an open-source software tool, pycabnn, that is dedicated to generating an anatomical model, which serves as the basis of a full network model.

Author Correction: The choroid plexus is an important circadian clock component.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.