Effect of Variations in Gap Junctional Coupling on the Frequency of Oscillatory Action Potentials in a Smooth Muscle Syncytium

Gap junctions provide pathways for intercellular communication between adjacent cells, allowing exchange of ions and small molecules. Based on the constituent protein subunits, gap junctions are classified into different subtypes varying in their properties such as unitary conductances, sensitivity to transjunctional voltage, and gating kinetics. Gap junctions couple cells electrically, and therefore the electrical activity originating in one cell can affect and modulate the electrical activity in adjacent cells. Action potentials can propagate through networks of such electrically coupled cells, and this spread is influenced by the nature of gap junctional coupling. Our study aims to computationally explore the effect of differences in gap junctional properties on oscillating action potentials in electrically coupled tissues. Further, we also explore variations in the biophysical environment by altering the size of the syncytium, the location of the pacemaking cell, as well as the occurrence of multiple pacemaking cells within the same syncytium. Our simulation results suggest that the frequency of oscillations is governed by the extent of coupling between cells and the gating kinetics of different gap junction subtypes. The location of pacemaking cells is found to alter the syncytial behavior, and when multiple oscillators are present, there exists an interplay between the oscillator frequency and their relative location within the syncytium. Such variations in the frequency of oscillations can have important implications for the physiological functioning of syncytial tissues.

Modeling the role of gap junctions between excitatory neurons in the developing visual cortex

Recent experiments in the developing mammalian visual cortex have revealed that gap junctions couple excitatory cells and potentially influence the formation of chemical synapses. In particular, cells that were coupled by a gap junction during development tend to share an orientation preference and are preferentially coupled by a chemical synapse in the adult cortex, a property that is diminished when gap junctions are blocked. In this work, we construct a simplified model of the developing mouse visual cortex including spike-timing-dependent plasticity of both the feedforward synaptic inputs and recurrent cortical synapses. We use this model to show that synchrony among gap-junction-coupled cells underlies their preference to form strong recurrent synapses and develop similar orientation preference; this effect decreases with an increase in coupling density. Additionally, we demonstrate that gap-junction coupling works, together with the relative timing of synaptic development of the feedforward and recurrent synapses, to determine the resulting cortical map of orientation preference.

Electrical synapse asymmetry results from, and masks, neuronal heterogeneity

Electrical synapses couple inhibitory neurons across the brain, underlying a variety of functions that are modifiable by activity. Despite recent advances, many basic functions and contributions of electrical synapses within neural circuitry remain underappreciated. Among these is the source and impact of electrical synapse asymmetry. Using multi-compartmental models of neurons coupled through dendritic electrical synapses, we investigated intrinsic factors that contribute to synaptic asymmetry and that result in modulation of spike time between coupled cells. We show that electrical synapse location along a dendrite, input resistance, internal dendritic resistance, or directional conduction of the electrical synapse itself each alter asymmetry as measured by coupling between cell somas. Conversely, true synapse asymmetry can be masked by each of these properties. Furthermore, we show that asymmetry alters the spiking timing and latency of coupled cells by up to tens of milliseconds, depending on direction of conduction or dendritic location of the electrical synapse. These simulations illustrate that causes of asymmetry are multifactorial, may not be apparent in somatic measurements of electrical coupling, influence dendritic processing, and produce a variety of outcomes on spike timing of coupled cells. Our findings highlight aspects of electrical synapses that should be considered in experimental demonstrations of coupling, and when assembling networks containing electrical synapses.

Accessible Battery Model with Aging Dependency

Designed to store and discharge electrical energy, rechargeable batteries consist of elementary storage cell assemblies. Aging is affected by various aggravating factors, mainly temperature. There are many electric or electrochemical models which describe their operation. Most standard models do not consider the aging phenomena of batteries and their consequences, while batteries deteriorate when used or stored. Precisely, most battery models do not simulate the influence of cell aging on other cells. The model presented in this paper incorporates aging and the effects of mutual interactions between cells. The model can be established based on four measurement points on the cell characteristic curve and allows the simulation of a single cell’s or multiple coupled cells’ behavior. The model can then be easily implemented in simulation software like Matlab.

Flipping the switch on the hub cell: Islet desynchronization through cell silencing

Pancreatic β cells, responsible for secreting insulin into the bloodstream and maintaining glucose homeostasis, are organized in the islets of Langerhans as clusters of electrically coupled cells. Gap junctions, connecting neighboring cells, coordinate the behavior of the islet, leading to the synchronized oscillations in the intracellular calcium and insulin secretion in healthy islets. Recent experimental work has shown that silencing special hub cells can lead to a disruption in the coordinated behavior, calling into question the democratic paradigm of islet insulin secretion with more or less equal input from each β cell. Islets were shown to have scale-free functional connectivity and a hub cell whose silencing would lead to a loss of functional connectivity and activity in the islet. A mechanistic model representing the electrical and calcium dynamics of β cells during insulin secretion was applied to a network of cells connected by gap junctions to test the hypothesis of hub cells. Functional connectivity networks were built from the simulated calcium traces, with some networks classified as scale-free, confirming experimental results. Potential hub cells were identified using previously defined centrality measures, but silencing them was unable to desynchronize the islet. Instead, switch cells, which were able to turn off the activity of the islet but were not highly functionally connected, were found via systematically silencing each cell in the network.

Trade-offs and design principles in the spatial organization of catalytic particles

Spatial organization of catalytic particles is ubiquitous in biological systems across different length scales, from enzyme complexes to metabolically coupled cells. Despite the different scales, these systems share common features of localized reactions with partially hindered diffusive transport, determined by the collective arrangement of the catalysts. Yet it remains largely unexplored how different arrangements affect the interplay between the reaction and transport dynamics, which ultimately determines the flux through the reaction pathway. Here we show that two fundamental trade-offs arise, the first between efficient inter-catalyst transport and depletion of substrate, and the second between steric confinement of intermediate products and accessibility of catalysts to substrate. We use a model reaction pathway to characterize the general design principles for the arrangement of catalysts that emerge from the interplay of these trade-offs. We find that the question of optimal catalyst arrangements generalizes the famous Thomson problem of electrostatics.

Idealized model of the developing visual cortex

Recent experiments in the developing mammalian visual cortex have revealed that gap junctions couple excitatory cells and potentially influence the formation of chemical synapses. Though gap junctions between inhibitory cells are ubiquitous in the adult cortex, and their presence has been shown to promote synchronous network firing, their function among excitatory, pyramidal cells remains poorly understood. During development, pyramidal cells that were derived from the same progenitor cell, called sister cells, are preferentially connected by a gap junction during the first postnatal week, while chemical synapses are still being formed. Additionally, these sister cells tend to share an orientation preference and a chemical synapse in the adult cortex, a property that is diminished when gap junctions are blocked. In this work, we construct an idealized model of the mouse visual cortex during the first two postnatal weeks of development to analyze the response properties of gap-junction-coupled cells and their effect on synaptic plasticity. Further, as an application of this model, we investigate the interplay of gap-junction coupling and synaptic plasticity on the order, or organization, of the resulting cortical map of orientation preference.Author summaryGap junctions, or sites of direct electrical connections between neurons, have a significant presence in the cortex, both during development and in adulthood. Their primary function during either of these periods, however, is still poorly understood. In the adult cortex, gap junctions between local, inhibitory neurons have been shown to promote synchronous firing, a network characteristic thought to be important for learning, attention, and memory. During development, gap junctions between excitatory, pyramidal cells, have been conjectured to play a role in synaptic plasticity and the formation of cortical circuits. In the visual cortex, where neurons exhibit tuned responses to properties of visual input such as orientation and direction, recent experiments show that excitatory cells are coupled by gap junctions during the first postnatal week and are replaced by chemical synapses during the second week. In this work, we explore the possible contribution of gap-junction coupling during development to the formation of chemical synapses both into the visual cortex from the thalamus and within the visual cortex between cortical cells. Specifically, within a mathematical model of the visual cortex during development, we identify the response properties of gap-junction-coupled cells and their influence on the formation of the cortical map of orientation preference.