Postactivation potentiation models of memory

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Most neuroscientists now believe that information is stored in the brain as an alteration in the connections (synapses) between brain cells (neurons).  This allows the restructuring of the circuitry that ultimately codes the memory.  These altered connections, however, are highly distributed, and they are embedded in a matrix of millions of connections that remain unaltered.  It is not only difficult to determine which connections are affected, we often cannot be certain which neurons, or even which groups of neurons, are participating in the storage process.  As a result, it is extraordinarily difficult to study the physiological mechanisms of real memory.  An alternative approach is to study the mechanisms of other phenomena that may utilize the same or similar mechanisms, particularly those that yield a controlled alteration of synaptic connectivity.  One such phenomenon is long-term potentiation (LTP).  If certain patterns of electrical stimulation are applied directly to specific neural pathways, the strength of the connections between that pathway and its neuronal target can be increased for long periods of time.  This phenomenon is amenable to experimental analysis, and it has received an enormous amount of attention in the neuroscience community over the last three decades.  Much of the work in my laboratory has been directed to the study of the rules that apply to this form of plasticity as it is expressed in cortical and subcortical brain regions.  The work that is proposed for the next grant term focuses on LTP in two systems, one involved in motor control and motor learning and the other in mood control and motivation.  This research will further our understanding of the mechanisms of synaptic plasticity and memory.  In addition, it should provide information that will facilitate the development of treatments for memory disorders and drug abuse.