Putting episodic memory in context: cellular mechanisms of environmental processing

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When we are asked to think of a memory we will often describe an important personal event such as a graduation, birthday or the first day of a new job. In memory research these types of memories for specific events or episodes from our lives are called episodic memories. These memories influence the kind of people we are and the way that we think about ourselves. Many of us have had the misfortune to experience how the loss of this type of memory can affect an elderly relative. In some types of dementia like Alzheimer's disease (AD) sufferers lose the ability to form new episodic memories. Patients with AD can remember detailed events from 20 years ago but have severe problems when asked to remember what happened to them earlier that day. This has a major impact on their ability to lead independent lives. In the UK approximately 465000 people have AD and this number will increase as the proportion of older people in our society increases. It is estimated that £338 billion pounds each year is spent across the world in providing care and treatment for people with dementia. Clearly this is a problem that needs addressing soon to reduce the burden on the NHS and the UK tax payer. One way to go about tackling the disease is to examine how the brain usually processes episodic memory as this will allow us to see which areas and mechanisms within the brain go wrong in the disease. Episodic memories are formed by combining the features of an event. These include where we were, what we were doing at the time and the features of the environment (e.g. was it inside or outside?). An area of the brain called the hippocampus is important for combining these pieces of information. People who have damage to their hippocampus have problems creating new episodic memories. However, we do not know how these different types of information reach the hippocampus. If we can find out the pathways in the brain that provide the hippocampus with the information that it needs to form episodic memories then we can start to examine further how these are affected in AD. At the moment we know a lot about how the brain processes spatial locations. The parts of the brain that allow us to know where we are have been described in the last 40 years in a lot of detail. However, we do not know how the other parts of episodic memory like the details of the environment in which we were are processed. The experiments in this application will address this problem by examining which parts of the brain are activated when changes to the features of an environment are experienced. We will go on to see how individual cells in these areas of the brain react to changes in the environment. Our specific aims are: 1. To determine which areas of the brain are active in response to the manipulation of contextual features and critical for the retrieval of memory for contextual information. 2. To determine which mechanisms within these brain areas are used to process contextual information. By addressing these aims we well gain a much better understanding of the mechanisms in the brain that process episodic memory. This will provide a tool for companies that produce treatments for these diseases to test their treatments effectively by examining these processes in models of the diseases. Ultimately it may help to reduce the burden on the NHS by helping to provide treatments for AD that target the early stages of the disease and so prevent significant brain damage from occurring.