Neurodegenerative diseases such as Alzheimer's disease (AD) are characterized by a severe and debilitating loss of memory. The observation that this and other disorders of memory involve pathology in the temporal lobe, has led to the idea of a 'Medial Temporal Lobe (MTL) memory system' consisting of the hippocampus (HC), perirhinal (PRh) and entorhinal cortices. These distinct structures appear to perform unique, yet complementary, memory-related functions. As the degeneration of AD is progressive, beginning with the rhinal cortex and later affecting the HC, isolating the specific contributions made by MTL structures to memory functioning is necessary for understanding the progression of memory deficits caused by AD. Thus, a main goal of the present research proposal is to clarify how these structures contribute to specific learning and memory processes. A second aspect of the neurobiology of AD that has received considerable attention is the degeneration of the cholinergic system. The cholinergic neurons that degenerate in AD project to the MTL structures described above.
A second aim of my proposed research, therefore, is to investigate the role of acetylcholine (ACh) to memory in these regions.
