Timing, Short-term Plasticity, and Metaplasticity of STP

Brain function depends on the communication between a vast number of neurons connected mostly via chemical synapses. The strength of these synapses changes over both short- and long-term time scales as a result of activity. Long-term changes in synaptic strength that last minutes, hours or more, including long-term potentiation (LTP) and long-term depression (LTD), have been carefully studied and are considered to be one of the neuronal bases of learning and memory. Synaptic strength also changes rapidly on the time scale of tens or hundreds of milliseconds in a use-dependent manner. This form of plasticity is termed short-term synaptic plasticity (STP). In contrast to LTP there has been significantly less work on STP. Short-term plasticity is generally considered as a presynaptic phenomenon although its mechanism has not been fully understood. STP has generally been considered to be governed in large part by baseline synaptic strength, therefore limiting its potential functional significance. It has been proposed, however, that STP can be "learned", specifically, that STP can be regulated by a novel learning rule in parallel to the associative learning rules governing baseline synaptic strength. Simulations in artificial neural networks have shown that their computational power is enhanced by STP plasticity. One goal of my work is to test this hypothesis using chronic stimulations in organotypic slices. I examined the induction of LTP in organotypic slices using optical pairing protocols, and tested the induction of metaplasticity of STP. Additionally, the development of STP in organotypic slices was also examined. Another part of the dissertation focused on the function of STP in temporal processing, especially order selectivity of sensory events. Here experimental evidence of in vitro order-selective neurons is provided. This finding supports a potential role for STP in the formation of temporally-selective responses. Overall my results add to the current understanding of the development, function, and regulation of short-term synaptic plasticity