Hippocampal bidirectional plasticity arising from transitions in a synaptic ensemble

Daniel H. O'Connor, Gayle M. Wittenberg, and Samuel S.-H. Wang

Princeton University

In bidirectional synaptic plasticity, change in synaptic strength has been observed to occur in graded amounts of potentiation or depression. However, measurements are almost always made from ensembles of synapses; this is true even in recordings from connected pairs of neurons. Such measurements therefore represent the sum of many single-synapse potentiation or depression events occurring at once. This point of view suggests that it may be possible to dissect bidirectional plasticity into separate processes of potentiation and depression/depotentiation. We tested this at the Schaffer collateral-CA1 synapse by driving synaptic ensembles into conditions from which only potentiation or depression/depotentiation are possible. When LTP is saturated with theta-burst stimulation or its induction blocked with the kinase inhibitor K252a, only long-term depression (LTD) or depotentiation can be induced. Conversely, when LTD is saturated or its induction blocked with the phosphatase inhibitor okadaic acid, only LTP can be induced. From a fully potentiated state, or in the presence of K252a, stimulus frequencies of 1 Hz or higher lead to LTD/depotentiation. From a fully depressed state, or after treatment with okadaic acid, stimulus frequencies of 5 Hz or higher lead to LTP. To account for our data we present a model of bidirectional synaptic plasticity in which synapses begin from a mixture of low-strength, high-strength, and recently-potentiated states.