kCSD-python, reliable current source density estimation with quality control.

Interpretation of extracellular recordings can be challenging due to the long range of electric field. This challenge can be mitigated by estimating the current source density (CSD). Here we introduce kCSD-python, an open Python package implementing Kernel Current Source Density (kCSD) method and related tools to facilitate CSD analysis of experimental data and the interpretation of results.

Making time and space for calcium control of neuron activity.

Calcium directly controls or indirectly regulates numerous functions that are critical for neuronal network activity. Intracellular calcium concentration is tightly regulated by numerous molecular mechanisms because spatial domains and temporal dynamics (not just peak amplitude) are critical for calcium control of synaptic plasticity and ion channel activation, which in turn determine neuron spiking activity. The computational models investigating calcium control are valuable because experiments achieving high spatial and temporal resolution simultaneously are technically unfeasible.

Social deficits in BTBR T+ Itpr3tf/J mice vary with ecological validity of the test.

Translational value of mouse models of neuropsychiatric disorders depends heavily on the accuracy with which they replicate symptoms observed in the human population. In mouse models of autism spectrum disorder (ASD) these include, among others, social affiliation, and communication deficits as well as impairments in understanding and perception of others. Most studies addressing these issues in the BTBR T+ Itpr3tf/J mouse, an idiopathic model of ASD, were based on short dyadic interactions of often non-familiar partners placed in a novel environment.

Brain size, gut size and cognitive abilities: the energy trade-offs tested in artificial selection experiment.

The enlarged brains of homeotherms bring behavioural advantages, but also incur high energy expenditures. The 'expensive brain' (EB) hypothesis posits that the energetic costs of the enlarged brain and the resulting increased cognitive abilities (CA) were met by either increased energy turnover or reduced allocation to other expensive organs, such as the gut. We tested the EB hypothesis by analysing correlated responses to selection in an experimental evolution model system, which comprises line types of laboratory mice selected for high or low basal metabolic rate (BMR), maximum (VO) metabolic rates and random-bred (unselected) lines.

Temporal pattern and synergy influence activity of ERK signaling pathways during L-LTP induction.

Long-lasting long-term potentiation (L-LTP) is a cellular mechanism of learning and memory storage. Studies have demonstrated a requirement for extracellular signal-regulated kinase (ERK) activation in L-LTP produced by a diversity of temporal stimulation patterns. Multiple signaling pathways converge to activate ERK, with different pathways being required for different stimulation patterns.

What we can and what we cannot see with extracellular multielectrodes.

Extracellular recording is an accessible technique used in animals and humans to study the brain physiology and pathology. As the number of recording channels and their density grows it is natural to ask how much improvement the additional channels bring in and how we can optimally use the new capabilities for monitoring the brain. Here we show that for any given distribution of electrodes we can establish exactly what information about current sources in the brain can be recovered and what information is strictly unobservable.

From membrane receptors to protein synthesis and actin cytoskeleton: Mechanisms underlying long lasting forms of synaptic plasticity.

Synaptic plasticity, the activity dependent change in synaptic strength, forms the molecular foundation of learning and memory. Synaptic plasticity includes structural changes, with spines changing their size to accomodate insertion and removal of postynaptic receptors, which are correlated with functional changes. Of particular relevance for memory storage are the long lasting forms of synaptic plasticity which are protein synthesis dependent.

Inhibition enhances spatially-specific calcium encoding of synaptic input patterns in a biologically constrained model.

Synaptic plasticity, which underlies learning and memory, depends on calcium elevation in neurons, but the precise relationship between calcium and spatiotemporal patterns of synaptic inputs is unclear. Here, we develop a biologically realistic computational model of striatal spiny projection neurons with sophisticated calcium dynamics, based on data from rodents of both sexes, to investigate how spatiotemporally clustered and distributed excitatory and inhibitory inputs affect spine calcium. We demonstrate that coordinated excitatory synaptic inputs evoke enhanced calcium elevation specific to stimulated spines, with lower but physiologically relevant calcium elevation in nearby non-stimulated spines.

Parameter Optimization Using Covariance Matrix Adaptation-Evolutionary Strategy (CMA-ES), an Approach to Investigate Differences in Channel Properties Between Neuron Subtypes.

Computational models in neuroscience can be used to predict causal relationships between biological mechanisms in neurons and networks, such as the effect of blocking an ion channel or synaptic connection on neuron activity. Since developing a biophysically realistic, single neuron model is exceedingly difficult, software has been developed for automatically adjusting parameters of computational neuronal models. The ideal optimization software should work with commonly used neural simulation software; thus, we present software which works with models specified in declarative format for the MOOSE simulator.

Modulation of Spike-Timing Dependent Plasticity: Towards the Inclusion of a Third Factor in Computational Models.

In spike-timing dependent plasticity (STDP) change in synaptic strength depends on the timing of pre- vs. postsynaptic spiking activity. Since STDP is in compliance with Hebb's postulate, it is considered one of the major mechanisms of memory storage and recall.

β-adrenergic signaling broadly contributes to LTP induction.

Long-lasting forms of long-term potentiation (LTP) represent one of the major cellular mechanisms underlying learning and memory. One of the fundamental questions in the field of LTP is why different molecules are critical for long-lasting forms of LTP induced by diverse experimental protocols. Further complexity stems from spatial aspects of signaling networks, such that some molecules function in the dendrite and some are critical in the spine.

Calcium dynamics predict direction of synaptic plasticity in striatal spiny projection neurons.

The striatum is a major site of learning and memory formation for sensorimotor and cognitive association. One of the mechanisms used by the brain for memory storage is synaptic plasticity - the long-lasting, activity-dependent change in synaptic strength. All forms of synaptic plasticity require an elevation in intracellular calcium, and a common hypothesis is that the amplitude and duration of calcium transients can determine the direction of synaptic plasticity.

Molecular mechanisms underlying neuronal synaptic plasticity: systems biology meets computational neuroscience in the wilds of synaptic plasticity.

Interactions among signaling pathways that are activated by transmembrane receptors produce complex networks and emergent dynamical behaviors that are implicated in synaptic plasticity. Temporal dynamics and spatial aspects are critical determinants of cell responses such as synaptic plasticity, although the mapping between spatiotemporal activity pattern and direction of synaptic plasticity is not completely understood. Computational modeling of neuronal signaling pathways has significantly contributed to understanding signaling pathways underlying synaptic plasticity.

Depressing synapse as a detector of frequency change.

In this article we discuss the short-term synaptic depression using a mathematical model. We derive the model of synaptic depression caused by the depletion of synaptic vesicles for the case of infinitely short stimulation time and show that the analytical formulas for the postsynaptic potential (PSP) and kinetic functions take simple closed form. A solution in this form allows an analysis of the characteristics of depression as a function of the models parameters and the derivation of analytic formulas for measures of short time synaptic depression commonly used in experimental studies.