Perirhinal neuronal activity and recognition memory mechanisms

Recognition memory, being able to judge that something has happened or been encountered previously, is essential to normal everyday life, including both employment and leisure pursuits. When the judgement of prior occurrence is impaired, as for example in the many sufferers from Alzheimer's disease, questions, statements and tasks are inappropriately repeated. Previous work has established that it is possible to study the processes underlying recognition memory in rats, and that these processes involve a specific brain region in the temporal lobe, the perirhinal cortex. The proposed work will determine how neuronal activity in this brain region signals information of importance to recognition memory and how such signalling is changed by highly selective drugs that are known to impair recognition memory. The drugs to be used will block specific types of glutamate receptors: glutamate receptors are essential to the way most neurons communicate with other neurons. Moreover, glutamate receptors are implicated in synaptic plastic processes that change how neurons interconnect and so potentially underlie memory. Their study is therefore critical to understanding how information necessary to recognition memory is processed and stored. The key goals are to determine what is being signalled by different types of perirhinal neurons and hence the different contributions of different types of such neurons to recognition memory, how these signals are changed in different ways by blocking different types of glutamate receptors, and to investigate the relationship of such signal changes to what is known of synaptic plastic processes. The information obtained will advance understanding of the neural basis of recognition memory.

To elucidate the neuronal substrates of recognition memory, multiple single neuronal recordings will be made from rats presented with novel and familiar visual stimuli. Recordings will be made from the perirhinal cortex, which is crucial to the familiarity discrimination component of recognition memory. Long-term recordings will be made to determine the properties of different types of perirhinal neurons in relation to recognition memory. Changes in the activity of neurons signalling information related to the prior occurrence of stimuli will be related to the local delivery of selective glutamate receptor antagonists that produce different patterns of recognition memory loss. The key goals are: (i) to provide a description of neuronal activity underlying familiarity discrimination; (ii) to determine how such activity is changed by selective antagonists of specific types of glutamate receptor (NMDA and kainate); (iii) thereby to provide an explanation for the different recognition memory impairments produced by kainate and NMDA glutamate receptor antagonists through their actions on neurons with specific response patterns; (iv) to relate different types of neuronal response changes to the known actions of the antagonists on perirhinal plasticity mechanisms; and (v) thereby to increase understanding of the neural basis of recognition memory.