Remediation of Cholinergic Depletion Effects on Cortical Functions with Neurotrophins

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Prior studies have show that when the neurotransmitter acetylcholine is reduced significantly in the cortex of the brain, a cascade of effects is observed in physiological and molecular systems that underlie learning and memory. These effects include changes in neural firing rates and in the expression of non-cholinergic neurotransmitters and synaptic proteins. Thus, two possibilities are suggested for the neural basis of memory: that acetylcholine alone may be responsible, or that it acts in concert with non-cholinergic neurotransmitters and synaptic proteins. The purpose of these studies is to determine whether the mechanisms of learning and memory can be preserved when the cascade of effects of non-cholinergic neural systems is prevented after the loss of acetylcholine. Therefore, acetylcholine in the cortex will be selectively removed and non-cholinergic neurotransmitters and synaptic proteins will be preserved by the application of neurotrophins, a class of brain proteins well known for aiding in the maintenance and survival of cortical neurons challenged by unfavorable conditions. Then the capacity of cortical neurons to undergo changes like those that take place in learning and memory will be determined. These studies are important for understanding the physiological and molecular bases of learning and memory.