Understanding the neural basis of recognition memory in the rat: A functional analysis

Recognition memory is essential to every day life. It involves our ability to judge whether or not we have encountered a stimulus previously. To make these judgements we are able to use a range of different memory processes. For example, we can make one type of judgements if a stimulus is completely new, i.e. never been seen before; we can make a different type of judgement if the stimulus is familiar, depending on whether we have seen it quite recently, or a long time ago; finally and we can make a third type of recognition memory judgements based on whether we have seen a stimulus within a particular environment, location or context. The hypothesis of this proposal is that these different memory processes are controlled by different regions of the brain, the perirhinal cortex, the prefrontal cortex and the hippocampus, potentially operating in a network. The aim of the experiments is firstly to understand which of these brain regions involved in which type of memory process, and secondly to investigate whether these brain regions are co-operating within a memory system. In addition we plan to investigate whether the neurotransmitter glutamate is important for communication between cells in the particular regions of the brain during the processing of information necessary for normal recognition memory function.

The process of recogntion memory may be subdivided into judgements made on the basis of familiairity discrimination, recency and/or associative recall. The aim of this proposal is to examine whether these cognitive processes are mediated by distinct regions of the brain, namely the perirhinal cortex, the prefrontal cortex and the hippocampus operating within an integrated neural network. The proposal seeks to test his hypothesis using an integrative approach combining both behavioural and cellular methodologies. The effects of disconnecting the perirhinal cortex, the prefrontal cortex and hippocampus will be investigated using behavioural tests of recognition memory function. In addition measurements of neuronal activation will also be made using immunohistochemical imaging of the protein products (Fos) of the immediate early gene c-fos to determine the functional dependencies of neural regions following the lesions. A systematic examination of the role of the glutamate system in the acquisition, consolidation and retrieval of recognition memory will also be made. To achieve this aim antagonists specific to distinct glutamate receptor subtypes will be administered intracerebrally into the perirhinal, prefrontal cortices and the hippocampus, or into multiple regions, at specific stages of the recognition memory tasks. By using two levels of experimental analysis it will be possible to obtain a greater understanding of the functional neuroanatomy of recognition memory.