 
| |
|
| |
|
| |
|
| |
Our interpretation of cholinergic function as a rate modulator within the cortico-hippocampal model has several implications. For example, we expect that if lowering hippocampal learning rates retards learning, increasing learning rates may speed up behavioral learning, consistent with data showing that drugs which enhance the effects of acetylcholine called cholinergic agonists can improve learning in subjects with abnormally reduced levels of brain acetylcholine. This is an area of great interest in the study of age-related memory deficits because it is commonly found that the levels of cholinergic input to the hippocampus from the medial septum decrease with age, both in patients with Alzheimers Dementia as well as in normal aged individuals.
Because cholinergic enhancement appears to offset some memory deficits in aging, some people have hoped that these same drugs, if given to people or animals with normal learning and memory abilities, might produce supernormal learning. Experimental studies with normal humans, however, have failed to see a supernormal behavioral enhancement effect from these cholinergic enhancement drugs. Why should these drugs enhance learning in people with depressed cholinergic function, but not normal people? An insight into this problem can be gained from the theoretical dose-response curves in our model. Increasing hippocampal learning rates beyond some optimal level in the model results in degraded learning because the network becomes unstable when the changes at the node-to-node associations occur too quickly. As illustrated in Figure 14 with both actual and simulated dose-response curves in monkeys for a cholinergic agonist, physostygmine, our model provides a computational interpretation of a common, but often puzzling, empirical finding: While cholinergic agonists at moderate doses tend to improve learning, higher doses may result in either no facilitation or an impairment in learning.
As we noted earlier, loss of cholinergic inputs to the hippocampus is a key aspect of Alzheimers Dementia, and also the target for all of the Alzheimer Dementia drugs currently available. However, Alzheimers Dementia also involves the direct destruction of neuronal connections in the hippocampus and entorhinal cortex, resulting in a marked loss of volume in these brain regions. Our ongoing efforts aim at using our theories and behavioral tasks to detect and predict the onset of Alzheimers Dementia.