Suhita Nadkarni

Dressed neurons: modeling neural-glial interactions.

Based on recent experimental data, we design a model for neuronal membrane potentials that incorporates the influence of the surrounding glia (dressed neurons). A neurotransmitter released into the synaptic cleft triggers a Ca(2+) response in nearby glial cells that spreads as a Ca(2+) wave and interacts with other synapses via the release of glutamate from astrocytes. We consider the simple case of a neuron-glia circuit that consists of a single neuron that triggers a Ca(2+) response in the glial cell which in turn feeds back into synapses of the same neuron. It is shown that persistent spiking can occur if the glutamate receptors on the astrocytes are overexpressed--a condition that has been reported from patients suffering from mesial-lobe epilepsy.

Astrocytes Optimize the Synaptic Transmission of Information

Chemical synapses transmit information via the release of neurotransmitter-filled vesicles from the presynaptic terminal. Using computational modeling, we predict that the limited availability of neurotransmitter resources in combination with the spontaneous release of vesicles limits the maximum degree of enhancement of synaptic transmission. This gives rise to an optimal tuning that depends on the number of active zones. There is strong experimental evidence that astrocytes that enwrap synapses can modulate the probabilities of vesicle release through bidirectional signaling and hence regulate synaptic transmission. For low-fidelity hippocampal synapses, which typically have only one or two active zones, the predicted optimal values lie close to those determined by experimentally measured astrocytic feedback, suggesting that astrocytes optimize synaptic transmission of information.

SYNAPTIC INHIBITION AND PATHOLOGIC HYPEREXCITABILITY THROUGH ENHANCED NEURON-ASTROCYTE INTERACTION: A MODELING STUDY

Recently, upregulation of metabotropic glutamate receptors (mGluRs) on hippocampal astrocytes in epileptic tissues has become part of the etiology of epilepsy and suggests the involvement of astrocytes in the disease. Through computational modeling, we have shown in previous work that upregulated mGluRs on astrocytes can give rise to positive feedback in closed loop neuron-astrocyte circuits with epilepsy-type spontaneous neuronal spiking. In this paper we further quantify the necessary degree of upregulation of astrocytic mGluRs, relate it to recent clinical and experimental studies, and address through computational modeling the role of synaptic inhibition through interneurons in this form of hyperexcitability. We conclude that inhibitive circuitry cannot tame this form of hyperexcitability.

Thermal activation by power-limited coloured noise

We consider thermal activation in a bistable potential in the presence of correlated (Ornstein–Uhlenbeck) noise. Escape rates are discussed as a function of the correlation time of the noise at a constant variance of the noise. In contrast to a large body of previous work, where the variance of the noise decreases with increasing correlation time of the noise, we find a bell-shaped curve for the escape rate with a vanishing rate at zero and infinite correlation times. We further calculate threshold crossing rates driven by energy-constrained coloured noise.

Mathematical modeling of intracellular and intercellular calcium signaling

Publisher Summary This chapter reviews that billions of neurons, interconnected to a large network, perform numerous cognitive and regulatory tasks. Most work on the modeling of brain functions is based on the modelling of neuronal networks. The vast majority of cells in the brain, however, are nonneuronal cells or glial cells; about 90% of all brain cells are glial cells. Among the several types of glial cells, the astrocytes are known to carry out many important functions; several of them in interactions with neurons. The chapter highlights that astrocytes listen to neuronal chatter at the synapses and in turn can modulate neuronal dynamics at the same synapse or over some distance. As neurons fire, glutamate is released into the synaptic cleft that is partially lined by the metabotropic glutamate receptors of the synaptic astrocytes. Upon binding of glutamate to the astrocyte, inositol 1,4,5-triphosphate (IP 3 ) is released into the intracellular space. IP 3 in turn binds to the IP 3 receptor of the endoplasmic reticulum (ER) and Ca2 + is released from the ER into the cytosol. As described in more detail below, such Ca2 + release can occur in forms of intracellular Ca2 + waves. The Ca2 + wave can propagate across the cell membrane, through the extracellular space into adjacent astrocytes. Elevated Ca2 + concentrations in synaptic astrocytes generate extracellular glutamate that can modulate the neuronal synapse by generating additional inward currents. The chapter also reviews recent progress in mathematical modeling of intracellular and intercellular Ca2 + signaling in general, and in the context of astrocytes and their control of synaptic plasticity.