Computational Study of Astroglial Calcium Homeostasis in a Semi-isolated Synaptic Cleft

Astrocytes can affect neuronal communication by controlling extracellular ionic concentration levels. In the hippocampus, astrocytes have an intimate relationship with neuronal synapses, enwrapping the synapse tightly to prevent chemical diffusion between synapses, a phenomenon known as semi-isolated synapses. Calcium (Ca2+) is known to enhance neurotransmitter release at excitatory synapses and release is dependent on levels of Ca2+ in the perisynaptic environment. Astrocytes have a great influence on Ca2+ levels at semi-isolated synapses, thus, they can affect neuronal transmission through control of synaptic Ca2+ levels. The perisynaptic astrocytic processes that semi-isolate synapses are exceedingly thin, typically having a diameter less than 100nm, therefore, these processes are most likely devoid of intracellular organelles and therefore, Ca2+ stores. Astrocytes possess many transmembrane proteins that can traffic Ca2+ into and out of the cell, with the plasma membrane ATPase and the sodium/calcium exchanger being the main transporters capable of carrying Ca2+ across the plasma membrane in large quantities.
The main aim of this research is to capture a more complete astroglial Ca2+ pathway as this may be important for understanding biological processes involving Ca2+ such as synaptic transmission, plasticity and ultimately learning. We use a computational approach to capture the ionic dynamics in a semi isolated synapse, with particular focus on Ca2+ dynamics. The model presented here is an extension of a recently published model that hypothesises the formation of Ca2+ microdomains in perisynaptic astrocytes. We take this hypothesis further and show that these Ca2+ microdomains can act as a local supply of Ca2+ to the synaptic cleft during periods of sustained excitability.