UNIVERSITY OF MASSACHUSETTS

Memory is probably one of the most widely studied neuronal phenomena since it is required for all living organisms to function efficiently in known and unknown environments. It has recently been proposed that impairment of memory formation in human beings addicted to drugs is responsible in part for some of the most deleterious long-term effects of these drugs (relapse and compulsive drug seeking behaviors).Nucleus accumbens has long been identified as a key brain region in addiction to drugs of abuse like alcohol. To date a number of membrane proteins (channels and receptors) have been identified as being modulated by alcohol in this structure. In this proposal, we will shift our focus on a newly discover feature, i.e. backpropagating action potentials, of nucleus accumbens medium spiny neurons and their role in mediating alcohol effects. Backpropagating action potentials are generated in the soma before invading retrogradly the dendritic arborization. Although direct evidence of the existence of these potentials in several brain regions, including the NAcc, appeared only recently, they have already been endowed with a major role in shaping synaptic plasticity. These action potentials are critical since they inform the dendritic compartment, at all time, about the level of excitability and the output of neurons. As such they help to determine the strength of the dendritic synapses. In this proposal, we will examine their contribution in two forms of synaptic plasticity (long-term depression and potentiation) and we hypthesize that alcohol modulates synaptic strength through their effects on backpropagating action potentials.

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