Jiajia Li

Dynamic transition of neuronal firing induced by abnormal astrocytic glutamate oscillation.

The gliotransmitter glutamate released from astrocytes can modulate neuronal firing by activating neuronal N-methyl-D-aspartic acid (NMDA) receptors. This enables astrocytic glutamate(AG) to be involved in neuronal physiological and pathological functions. Based on empirical results and classical neuron-glial “tripartite synapse” model, we propose a practical model to describe extracellular AG oscillation, in which the fluctuation of AG depends on the threshold of calcium concentration, and the effect of AG degradation is considered as well. We predict the seizure-like discharges under the dysfunction of AG degradation duration. Consistent with our prediction, the suppression of AG uptake by astrocytic transporters, which operates by modulating the AG degradation process, can account for the emergence of epilepsy.

Noise-induced spatiotemporal patterns in Hodgkin–Huxley neuronal network

The effect of noise on the pattern selection in a regular network of Hodgkin–Huxley neurons is investigated, and the transition of pattern in the network is measured from subexcitable to excitable media. Extensive numerical results confirm that kinds of travelling wave such as spiral wave, circle wave and target wave could be developed and kept alive in the subexcitable network due to the noise. In the case of excitable media under noise, the developed spiral wave and target wave could coexist and new target-like wave is induced near to the border of media. The averaged membrane potentials over all neurons in the network are calculated to detect the periodicity of the time series and the generated traveling wave. Furthermore, the firing probabilities of neurons in networks are also calculated to analyze the collective behavior of networks.

The influence of potassium concentration on epileptic seizures in a coupled neuronal model in the hippocampus

Experiments on hippocampal slices have recorded that a novel pattern of epileptic seizures with alternating excitatory and inhibitory activities in the CA1 region can be induced by an elevated potassium ion (K+) concentration in the extracellular space between neurons and astrocytes (ECS-NA). To explore the intrinsic effects of the factors (such as glial K+ uptake, Na+–K+-ATPase, the K+ concentration of the bath solution, and K+ lateral diffusion) influencing K+ concentration in the ECS-NA on the epileptic seizures recorded in previous experiments, we present a coupled model composed of excitatory and inhibitory neurons and glia in the CA1 region. Bifurcation diagrams showing the glial K+ uptake strength with either the Na+–K+-ATPase pump strength or the bath solution K+ concentration are obtained for neural epileptic seizures. The K+ lateral diffusion leads to epileptic seizure in neurons only when the synaptic conductance values of the excitatory and inhibitory neurons are within an appropriate range. Finally, we propose an energy factor to measure the metabolic demand during neuron firing, and the results show that different energy demands for the normal discharges and the pathological epileptic seizures of the coupled neurons.

Astrocytic Gliotransmitter: Diffusion Dynamics and Induction of Information Processing on Tripartite Synapses

Astrocytes have important functions in the central nervous system (CNS) and are significant in our understanding of the neuronal network. Astrocytes modulate neuronal firings at both single cell level of tripartite synapses and the neuron-glial network level. Astrocytes release adenosine triphosphate (ATP) and glutamate into the neuron-glial network. These gliotransmitters diffuse over the network to form long distance signals to regulate neuron firings. In this paper, we study a neuron-glial network model that includes a diffusion of astrocytic ATP and glutamate to investigate how long distance diffusion of the gliotransmitters affects the information processing in a neuronal network. We find that gliotransmitters diffusion can compensate for the failure of information processing of interneuron network firings induced by defectively coupled synapses. Moreover, we find that calcium waves in astrocyte network and firings in interneuron network are both sensitive to the glutamate diffusion rate and feedback intensities of astrocytes on interneurons.

Astrocytic Kir4.1 channels and gap junctions account for spontaneous epileptic seizure

Experimental recordings in hippocampal slices indicate that astrocytic dysfunction may cause neuronal hyper-excitation or seizures. Considering that astrocytes play important roles in mediating local uptake and spatial buffering of K+ in the extracellular space of the cortical circuit, we constructed a novel model of an astrocyte-neuron network module consisting of a single compartment neuron and 4 surrounding connected astrocytes and including extracellular potassium dynamics. Next, we developed a new model function for the astrocyte gap junctions, connecting two astrocyte-neuron network modules. The function form and parameters of the gap junction were based on nonlinear regression fitting of a set of experimental data published in previous studies. Moreover, we have created numerical simulations using the above single astrocyte-neuron network module and the coupled astrocyte-neuron network modules. Our model validates previous experimental observations that both Kir4.1 channels and gap junctions play important roles in regulating the concentration of extracellular potassium. In addition, we also observe that changes in Kir4.1 channel conductance and gap junction strength induce spontaneous epileptic activity in the absence of external stimuli.

Firing Dynamics of Neurons in Hippocampus Under Epilepsy

The seizure-like activity in hippocampal CA1 region in brain is a primary clinical presentation for the temporal lobe epilepsy. Epileptic activities are highly related to excitability of interneurons and pyramidal cells in hippocampal region. In this paper, we introduced chemical synapses, and K+ lateral diffusion coupling into the CA1 neuronal model, and explored the neuronal firing modes under the epilepsy. Results show that pyramidal cells coupling with interneurons could produce a high frequency epileptic firing, and that the extracellular K+ lateral diffusion can evoke the epileptic activities, and the period of epileptic discharge will increase rapidly with increase of K+ lateral diffusing intensity.