The efficiency with which the activity of one neuron is transmitted across a synapse to another neuron is not static, but is known to change constantly, depending on the timing between the incoming action potentials. This phenomenon is called synaptic plasticity, and involves a variety of cell processes, operating on a wide range of time scales. While long-term forms of synaptic plasticity are believed to underlie learning and memory, my research is focused on short-term plasticity processes such as facilitation and depression, which have recently drawn great attention due to the role they play in regulating the activity dynamics of neural circuits on fast time scales (milliseconds to seconds). For example, Figure 1 illustrates the differential temporal filtering of spike train information by facilitating versus depressing synapses.

Apart from exploring the effect of synaptic depression and facilitation on network activity, I also investigate biological mechanisms underlying these phenomena. It is known that facilitation is caused by the accumulation of calcium ions at the synaptic terminal; in general, calcium influx is an established trigger for neurotransmitter release. However, it is still under debate how small amounts of residual calcium remaining after a single action potential can cause a dramatic increase in synaptic response to the next pulse. Answering this question depends on our understanding of the role that calcium buffers (intracellular molecules that bind calcium) play in regulating intracellular calcium diffusion. In particular, Figure 2 shows the facilitation of calcium transients produced by five consecutive pulses of activity, resulting from the saturation of calcium buffers, and demonstrates the interesting non-monotonic dependence of this effect on buffer concentration and its mobility. Understanding the intracellular buffered diffusion of calcium is important in the study of many other cell mechanisms, since calcium signals control a vast number of crucial cellular processes (collaborators: A. Sherman, NIH; R. Bertram, FSU; J.-W. Lin, Boston U; R.S. Zucker, UC Berkeley).