Synaptic plastic processes such as long-term potentiation (LTP) and long-term depression (LTD) play a central role in virtually all models that seek to explain learning and memory at a cellular level. Beyond even that, LTP and LTD are found in many brain areas and have been proposed to play a role in a wide range of neural functions and disorders. Neural functions from fear and emotion, through memory to addiction have been proposed to have a basis in these plastic processes. Therefore, the understanding of the mechanisms that underlie this plasticity will provide wide-ranging benefits not only to understanding normal brain function, but also to many neurological disorders. The study of LTP and LTD have been plagued by conflicting theories and experimental results that has in many cases slowed progress in understanding the underlying mechanism of these neuronal properties. Much of this confusion, we believe, has arisen from technical limitations of experiments that have, by necessity, relied exclusively on measures of synaptic plasticity in large populations of synapses. Since synapses can be found in a variety of plastic states, e.g. naive, potentiated, depressed, and populations of synapses almost certainly contain all these states and more, experimental manipulations may provide confusing results. Much as patch clamp recording, where the activity of a small number of ion channels could be recorded in isolation, revolutionized the study of ion channel function. the field of synaptic plasticity could benefit from experiments where very small numbers of synapses could be selectively studied and manipulated. In this proposal, we employ a method where we can record the activity of small numbers of synapses (1-10) identify their plastic state, and experimentally manipulate that state. By doing so, we can study the transitions between different plastic states in cases where we know the history of the synapses under study. In our preliminary studies, we have already clarified several issues relating to the mechanisms of synaptic plasticity and expect that the experiments in this proposal will greatly expand our knowledge of these mechanisms.
Showing the most recent 10 out of 14 publications
