Expression of Long-Term Plasticity at Individual Synapses in Hippocampus Is Graded, Bidirectional, and Mainly Presynaptic: Optical Quantal Analysis

Key aspects of the expression of long-term potentiation (LTP) and long-term depression (LTD) remain unresolved despite decades of investigation. Alterations in postsynaptic glutamate receptors are believed to contribute to the expression of various forms of LTP and LTD, but the relative importance of presynaptic mechanisms is controversial. In addition, while aggregate synaptic input to a cell can undergo sequential and graded (incremental) LTP and LTD, it has been suggested that individual synapses may only support binary changes between initial and modified levels of strength. We have addressed these issues by combining electrophysiological methods with two-photon optical quantal analysis of plasticity at individual active (non-silent) Schaffer collateral synapses on CA1 pyramidal neurons in acute slices of hippocampus from adolescent rats. We find that these synapses sustain graded, bidirectional long-term plasticity. Remarkably, changes in potency are small and insignificant; long-term plasticity at these synapses is expressed overwhelmingly via presynaptic changes in reliability of transmitter release.