Retroactive effect of dopamine on hippocampal spike timing-dependent plasticity

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How can the brain store our experiences in memory? And of all the events that we experience each day, why is it that some are remembered and others not? Many factors may influence how well we remember. Whether we remember a particular event or not is influenced not only by what happens during the event, but also by what happens after the event. For example, the presentation of a reward may help us remember the event that preceded the reward. In this proposal, we will study the basic mechanisms for how reward may influence memory. It is generally believed that memories are stored as changes in the connections between the nerve cells of the brain. This is known as synaptic plasticity. In this project, we will investigate the basic rules for how these changes are induced, and specifically, how a reward signal in the brain, dopamine, can influence this plasticity. To address these questions, we will use a new technique, known as optogenetics. This technique enables us to activate specific cell types using a laser. The specificity is achieved by expressing a light-sensitive protein in only one specific cell type. In this way, we can isolate a specific connection in the brain, and we can release dopamine specifically onto those connections. We will test the hypothesis that dopamine is capable of altering the rules of synaptic plasticity. Specifically, we will test whether dopamine is capable of modulating plasticity retroactively, and thus help explain how rewards may influence memory for events that led up to the reward. We will also investigate the molecular cascades that dopamine acts on to produce these changes in synaptic plasticity. The results should give us new insights into memory and could potentially open up new avenues for improving memory in ageing individuals and for treating memory disorder.