Evidence for a short-lived resonance state in enzyme catalysis via rate-equation convolution.

At the cellular level, all biological function relies on enzymes to provide catalytic acceleration of essential biochemical processes driving cellular metabolism. The enzyme is presumed to lower the activation energy barrier separating reactants from products, but the precise mechanism remains unresolved. Here we examine the temperature dependence of the enzyme-catalyzed dissociation of p-nitrophenyl-α-D-glucopyranoside (pNPG), a chromogenic analog for maltose, isomaltose, and sucrose disaccharide sugars, into p-nitrophenol (pNP) and glucose (monosaccharide).

Determination of Krogh Coefficient for Oxygen Consumption Measurement from Thin Slices of Rodent Cortical Tissue Using a Fick's Law Model of Diffusion.

To investigate the impact of experimental interventions on living biological tissue, ex vivo rodent brain slices are often used as a more controllable alternative to a live animal model. However, for meaningful results, the biological sample must be known to be healthy and viable. One of the gold-standard approaches to identifying tissue viability status is to measure the rate of tissue oxygen consumption under specific controlled conditions.

The molecular dynamics of possible inhibitors for SARS-CoV-2.

The novel coronavirus SARS-CoV-2, responsible for the present COVID-19 global pandemic, is known to bind to the angiotensin converting enzyme-2 (ACE2) receptor in human cells. A possible treatment of COVID-19 could involve blocking ACE2 and/or disabling the spike protein on the virus. Here, molecular dynamics simulations were performed to test the binding affinities of nine candidate compounds.

Analysis of the Hindriks and van Putten model for propofol anesthesia: Limitations and extensions.

We present a detailed analysis of the Hindriks and van Putten thalamocortical mean-field model for propofol anesthesia [NeuroImage 60(23), 2012]. The Hindriks and van Putten (HvP) model predicts increases in delta and alpha power for moderate (up to 130%) prolongation of GABA inhibitory response, corresponding to light anesthetic sedation. Our analysis reveals that, for deeper anesthetic effect, the model exhibits an unexpected abrupt jump in cortical activity from a low-firing state to an extremely high-firing stable state (∼250 spikes/s), and remains locked there even at GABA prolongations as high as 300% which would be expected to induce full comatose suppression of all firing activity.

Spinodal decomposition in a mean-field model of the cortex: Emergence of hexagonally symmetric activation patterns.

Spinodal decomposition is a well-known pattern-forming mechanism in metallurgic alloys, semiconductor crystals, and colloidal gels. In metallurgy, if a heated sample of a homogeneous Zn-Al alloy is suddenly quenched below a critical temperature, then the sample can spontaneously precipitate into inhomogenous textures of Zn- and Al-rich regions with significantly altered material properties such as ductility and hardness. Here we report on our recent discovery that a two-dimensional model of the human cortex with inhibitory diffusion can, under particular homogeneous initial conditions, exhibit a form of nonconserved spinodal decomposition in which regions of the cortex self-organize into hexagonally distributed binary patches of activity and inactivity.

Anesthesia modifies subthreshold critical slowing down in a stochastic Hodgkin-Huxley-like model with inhibitory synaptic input.

The dynamics of a stochastic type-I Hodgkin-Huxley-like point neuron model exposed to inhibitory synaptic noise are investigated as a function of distance from spiking threshold and the inhibitory influence of the general anesthetic agent propofol. The model is biologically motivated and includes the effects of intrinsic ion-channel noise via a stochastic differential equation description as well as inhibitory synaptic noise modeled as multiple Poisson-distributed impulse trains with saturating response functions. The effect of propofol on these synapses is incorporated through this drug's principal influence on fast inhibitory neurotransmission mediated by γ-aminobutyric acid (GABA) type-A receptors via reduction of the synaptic response decay rate.

Which System Variables Carry Robust Early Signs of Upcoming Phase Transition? An Ecological Example.

Growth of critical fluctuations prior to catastrophic state transition is generally regarded as a universal phenomenon, providing a valuable early warning signal in dynamical systems. Using an ecological fisheries model of three populations (juvenile prey J, adult prey A and predator P), a recent study has reported silent early warning signals obtained from P and A populations prior to saddle-node (SN) bifurcation, and thus concluded that early warning signals are not universal. By performing a full eigenvalue analysis of the same system we demonstrate that while J and P populations undergo SN bifurcation, A does not jump to a new state, so it is not expected to carry early warning signs.

From individual spiking neurons to population behavior: Systematic elimination of short-wavelength spatial modes.

Mean-field models of the brain approximate spiking dynamics by assuming that each neuron responds to its neighbors via a naive spatial average that neglects local fluctuations and correlations in firing activity. In this paper we address this issue by introducing a rigorous formalism to enable spatial coarse-graining of spiking dynamics, scaling from the microscopic level of a single type 1 (integrator) neuron to a macroscopic assembly of spiking neurons that are interconnected by chemical synapses and nearest-neighbor gap junctions. Spiking behavior at the single-neuron scale ℓ≈10μm is described by Wilson's two-variable conductance-based equations [H.

Channel-noise-induced critical slowing in the subthreshold Hodgkin-Huxley neuron.

The dynamics of a spiking neuron approaching threshold is investigated in the framework of Markov-chain models describing the random state-transitions of the underlying ion-channel proteins. We characterize subthreshold channel-noise-induced transmembrane potential fluctuations in both type-I (integrator) and type-II (resonator) parametrizations of the classic conductance-based Hodgkin-Huxley equations. As each neuron approaches spiking threshold from below, numerical simulations of stochastic trajectories demonstrate pronounced growth in amplitude simultaneous with decay in frequency of membrane voltage fluctuations induced by ion-channel state transitions.

Noise-induced precursors of state transitions in the stochastic Wilson-cowan model.

The Wilson-Cowan neural field equations describe the dynamical behavior of a 1-D continuum of excitatory and inhibitory cortical neural aggregates, using a pair of coupled integro-differential equations. Here we use bifurcation theory and small-noise linear stochastics to study the range of a phase transitions-sudden qualitative changes in the state of a dynamical system emerging from a bifurcation-accessible to the Wilson-Cowan network. Specifically, we examine saddle-node, Hopf, Turing, and Turing-Hopf instabilities.

EEG slow-wave coherence changes in propofol-induced general anesthesia: experiment and theory.

The electroencephalogram (EEG) patterns recorded during general anesthetic-induced coma are closely similar to those seen during slow-wave sleep, the deepest stage of natural sleep; both states show patterns dominated by large amplitude slow waves. Slow oscillations are believed to be important for memory consolidation during natural sleep. Tracking the emergence of slow-wave oscillations during transition to unconsciousness may help us to identify drug-induced alterations of the underlying brain state, and provide insight into the mechanisms of general anesthesia.

Frontal-temporal synchronization of EEG signals quantified by order patterns cross recurrence analysis during propofol anesthesia.

Characterizing brain dynamics during anesthesia is a main current challenge in anesthesia study. Several single channel electroencephalogram (EEG)-based commercial monitors like the Bispectral index (BIS) have suggested to examine EEG signal. But, the BIS index has obtained numerous critiques.

Simulations of pattern dynamics for reaction-diffusion systems via SIMULINK.

Background: Investigation of the nonlinear pattern dynamics of a reaction-diffusion system almost always requires numerical solution of the system's set of defining differential equations. Traditionally, this would be done by selecting an appropriate differential equation solver from a library of such solvers, then writing computer codes (in a programming language such as C or Matlab) to access the selected solver and display the integrated results as a function of space and time. This "code-based" approach is flexible and powerful, but requires a certain level of programming sophistication.

Gap junctions modulate seizures in a mean-field model of general anesthesia for the cortex.

During slow-wave sleep, general anesthesia, and generalized seizures, there is an absence of consciousness. These states are characterized by low-frequency large-amplitude traveling waves in scalp electroencephalogram. Therefore the oscillatory state might be an indication of failure to form coherent neuronal assemblies necessary for consciousness.

Investigation into the effect of the general anaesthetics etomidate and ketamine on long-range coupling of population activity in the mouse neocortical slice.

General anaesthetics have been hypothesised to ablate consciousness by decoupling intracortical neural connectivity. We explored this by investigating the effect of etomidate and ketamine on coupling of neural population activity using the low magnesium neocortical slice model. Four extracellular electrodes (50 μm) were positioned in mouse neocortical slices (400 μm thick) with varying separation.

Investigating paradoxical hysteresis effects in the mouse neocortical slice model.

Clinically, anesthetic drugs show hysteresis in the plasma drug concentrations at induction versus emergence from anesthesia induced unconsciousness. This is assumed to be the result of pharmacokinetic lag between the plasma and brain effect-site and vice versa. However, recent mathematical and experimental studies demonstrate that anesthetic hysteresis might be due in part to lag in the brain physiology, independent of drug transport delay - so-called "neural inertia".

Changes in frequency of seizure-like events in stimulated cortical slices.

Epilepsy affects nearly 3 million people in the United States alone. Given the fact that many people suffer from seizures that are intractable to pharmacological intervention, research groups are investigating the use of electrical stimulation to interact with and ameliorate symptoms of epileptic seizures. In mouse cortical slices made seizuregenic through chemical means, we applied precision controlled current pulses and measured local field potentials through a four point probe system to investigate the response of seizing tissue to electrical stimulation.

Connexin36 knockout mice display increased sensitivity to pentylenetetrazol-induced seizure-like behaviors.

Objective: Large-scale synchronous firing of neurons during seizures is modulated by electrotonic coupling between neurons via gap junctions. To explore roles for connexin36 (Cx36) gap junctions in seizures, we examined the seizure threshold of connexin36 knockout (Cx36KO) mice using a pentylenetetrazol (PTZ) model.

Methods: Mice (2-3months old) with Cx36 wildtype (WT) or Cx36KO genotype were treated with vehicle or 10-40mg/kg of the convulsant PTZ by intraperitoneal injection.

A mechanism for ultra-slow oscillations in the cortical default network.

When the brain is in its noncognitive "idling" state, functional MRI measurements reveal the activation of default cortical networks whose activity is suppressed during cognitive processing. This default or background mode is characterized by ultra-slow BOLD oscillations (∼0.05 Hz), signaling extremely slow cycling in cortical metabolic demand across distinct cortical regions.

An analysis of the transitions between down and up states of the cortical slow oscillation under urethane anaesthesia.

We study the dynamics of the transition between the low- and high-firing states of the cortical slow oscillation by using intracellular recordings of the membrane potential from cortical neurons of rats. We investigate the evidence for a bistability in assemblies of cortical neurons playing a major role in the maintenance of this oscillation. We show that the trajectory of a typical transition takes an approximately exponential form, equivalent to the response of a resistor-capacitor circuit to a step-change in input.

The electrocortical effects of enflurane: experiment and theory.

Background: High concentrations of enflurane will induce a characteristic electroencephalogram pattern consisting of periods of suppression alternating with large short paroxysmal epileptiform discharges (PEDs). In this study, we compared a theoretical computer model of this activity with real local field potential (LFP) data obtained from anesthetized rats.

Methods: After implantation of a high-density 8 x 8 electrode array in the visual cortex, the patterns of LFP and multiunit spike activity were recorded in rats during 0.

Excitatory effects of gap junction blockers on cerebral cortex seizure-like activity in rats and mice.

Purpose: The role of gap junctions in seizures is an area of intense research. Many groups have reported anticonvulsant effects of gap junction blockade, strengthening the case for a role for gap junctions in ictogenesis. The cerebral cortex is underrepresented in this body of research.

Modeling brain activation patterns for the default and cognitive states.

We argue that spatial patterns of cortical activation observed with EEG, MEG and fMRI might arise from spontaneous self-organisation of interacting populations of excitatory and inhibitory neurons. We examine the dynamical behavior of a mean-field cortical model that includes chemical and electrical (gap-junction) synapses, focusing on two limiting cases: the "slow-soma" limit with slow voltage feedback from soma to dendrite, and the "fast-soma" limit in which the feedback action of soma voltage onto dendrite reversal potentials is instantaneous. For slow soma-dendrite feedback, we find a low-frequency (approximately 1 Hz) dynamic Hopf instability, and a stationary Turing instability that catalyzes formation of patterned distributions of cortical firing-rate activity with pattern wavelength approximately 2 cm.