LTP: A mechanism for object-place learning in the prefrontal cortex ?

Recognition memory is essential to every day life. It involves our ability to judge whether or not we have encountered something previously. To make these judgements we are able to use a range of different memory processes. For example, we can make recognition memory judgement based upon whether we have seen a stimulus within a particular environment, location or context i.e. whether an object has been seen or encountered previously in a particular place. The hypothesis of this proposal is that this particular memory processes (called object-in-place memory) is controlled within a region of the brain, the prefrontal cortex. It has been proposed that the formation and storage of memory relies on the strengthening of the connections between neurones, and therefore increased communication between brain cells. The aim of the experiments is to understand the processes which may be occurring within brain cells in the prefrontal cortex which result in increased communication between them, and to examine whether the formation and storage of object-in-place memories requires these same processes. Such research willl allow a greater understanding of how we are able to learn and store memory information in the brain.

Understanding the neural bases of memory remains a major goal in neuroscience. Whilst learning is widely believed to depend on synaptic plasticity (such as long-term potentiation and depression; LTP and LTD) the precise relationships between learning and synaptic plasticity are still not well understood. Visual recognition memory, knowing whether a stimulus is novel or has been seen previously, is essential for normal everyday life. Recognition memory consists of at least 2 distinct components: familiarity discrimination and associative recall i.e. discriminations based upon the integration of object and spatial information.. These 2 components of recognition memory are mediated by distinct neural regions; the familiarity discrimination component relying on perirhinal cortex whilst the associative recall component most likely relies on prefrontal cortex. Familiarity discrimination is associated with a decrement in neuronal responsiveness in perirhinal cortex and the mechanisms underlying this decrement most likely rely on LTD-like changes in synaptic strength. In marked contrast it has recently been demonstrated that there is a lasting increase in the responsiveness of prefrontal cortex neurones in recognition memory. However, it is not known what synaptic changes underlie the increased neuronal responsiveness in prefrontal cortex or what synaptic changes underlie associative recall memory. Therefore, the proposed experiments will test the hypothesis that the mechanisms of induction, expression and maintenance of LTP are crucial for the increased neuronal responsiveness thought to underpin object association memory in PFC. Therefore this work, involving a range of different techniques and multi level analyses, is novel and important and presents a considerable opportunity to make advances into understanding the mechanisms of recognition memory