Use of Randomized Submaximal Glutamate Stimulus to Interpret Glial Effects on Neuronal Calcium Dynamics

The neuronal synapse is a dynamic functional unit which is composed of neurons and support glial cells, which provide the important function of glutamate re-uptake. We have previously described calcium dynamicsin neuronal cultures treated with toxic and non-toxic concentrations ofglutamate using single stimuli of micromolar glutamate . Here we investigated whether a pattern of multiple, submaximal glutamate stimulations at nanomolar concentrations of glutamate affected calcium dynamics in neuronal cultures with and without high glial content, and whether the order of addition of nanomolar glutamate affected calcium dynamics. Calcium is a key signaling ion involved in memory and learning with ionotropic glutamate receptors such as the N-methyl-D-aspartate receptors (NMDAR) on the neuronal membrane. 

 NMDARs are a major subtype of ionotropic receptors responsible for binding glutamate, the most abundant excitatory neurotransmitter (excitatory stimulus) in the human brain. Activation of NMDARs opens the ion channel at theplasma membrane to allow calcium influx into the cell cytosol. Calcium in its ionic form is very dynamic, especially in excitable cells such as muscle and brain cells, moving from the high concentration exterior of the cell to the much lower concentrations inside the cell where calcium is used as a second messenger.