Homeostatic synaptic plasticity through changes in presynaptic calcium influx.

Chronic perturbations of electrical activity within neural circuits lead to compensatory changes in synaptic strength collectively termed homeostatic synaptic plasticity. The postsynaptic mechanisms underlying these modifications have been characterized in some detail, but the presynaptic mechanisms that alter the efficiency of evoked neurotransmitter release are less clear. To investigate the role of presynaptic calcium influx, we have combined the use of two fluorescent proteins in cultured hippocampal neurons: a calcium reporter localized to synaptic vesicles, SyGCaMP2, and a reporter of vesicle fusion, SypHy. We find that a decrease in the activity of the network causes an increase in the amount of calcium entering the synaptic bouton in response to an action potential and an increase in the probability of vesicle fusion. Homeostatic changes in release probability varied as the third power of calcium influx. These results indicate that changes in the number and/or function of presynaptic calcium channels are major determinants of homeostatic changes in synaptic strength.