Controlling Effects of Astrocyte on Neuron Behavior in Tripartite Synapse Using VHDL–AMS

Astrocyte cells form the largest cell population in the brain and can influence neuron behavior. These cells provide appropriate feedback control in regulating neuronal activities in the Central Nervous System (CNS). This paper presents a set of equations as a model to describe the interactions between neurons and astrocyte. A VHDL–AMS-based tripartite synapse model that includes a pre-synaptic neuron, the synaptic terminal, a post-synaptic neuron, and an astrocyte cell is presented. In this model, the astrocyte acts as a controller module for neurons and can regulates the spiking activity of them. Simulation results show that by regulating the coupling coefficients of astrocytes, spiking frequency of neurons can be reduced and the activity of neuronal cells is modulated.

Dysregulation of Astrocyte Ion Homeostasis and Its Relevance for Stroke-Induced Brain Damage

Ischemic stroke is a leading cause of mortality and chronic disability. Either recovery or progression towards irreversible failure of neurons and astrocytes occurs within minutes to days, depending on remaining perfusion levels. Initial damage arises from energy depletion resulting in a failure to maintain homeostasis and ion gradients between extra- and intracellular spaces. Astrocytes play a key role in these processes and are thus central players in the dynamics towards recovery or progression of stroke-induced brain damage. Here, we present a synopsis of the pivotal functions of astrocytes at the tripartite synapse, which form the basis of physiological brain functioning. We summarize the evidence of astrocytic failure and its consequences under ischemic conditions. Special emphasis is put on the homeostasis and stroke-induced dysregulation of the major monovalent ions, namely Na+, K+, H+, and Cl-, and their involvement in maintenance of cellular volume and generation of cerebral edema.

Sleep-like behavior is a fundamental property of the tripartite synapse

The tripartite synapse, consisting of the presynaptic neuron, post-synaptic neuron, and an astrocyte, is considered to be the main locus of signaling between neurons in the brain.1,2 Neurotransmission is energetically very expensive3,4, and the primary neurotransmitter utilized for signaling is glutamate. It has been found that glutamate is also used as a substrate for energy generation.5,6 However, it is unclear what the relationship is between energy generation and availability of neurotransmitter during glutamatergic neurotransmission. Here we show that availability of energy, represented by adenosine triphosphate (ATP), and glutamate for neurotransmission are intimately related, and in fact determine the ability to signal at the tripartite synapse. Using a novel neurochemical mathematical model of the tripartite synapse, we found that glutamate concentrations for neurotransmission and ATP concentrations were interdependent, and their interplay controlled the firing pattern of the presynaptic terminal, as defined by synaptic vesicle release. Furthermore, we found that depending on the parameters chosen in the model, the tripartite synapse demonstrated behavior with limit cycles, alternating between high- and low-frequency firing rates. Our results show that complex behavior with high- and low-activity states, qualitatively meeting the characteristics of sleep7 emerges directly from the nature of the tripartite synapse, with glutamate and ATP concentrations serving as the signals for state changes. We anticipate that our model will serve as a starting point to further elucidate the energetics of neuronal and brain functioning, and eventually shed light on the fundamental question of the nature and necessity of sleep.