Science in Evolution The Cholinergic Story

In 1976, Peter Davies, who was examining autopsied brains of patients with Alzheimer's disease, reported the death of nerve cells that normally produced the neurotransmitter acetylcholine. Around the same time, David Drachman showed that administering scopolamine, which is an antagonist of acetylcholine, to normal people could produce memory impairment and other cognitive deficits that mimicked Alzheimer's disease. These discoveries began the race to develop an effective medication that could reverse the acetylcholine deficit seen in patients with Alzheimer's disease.

Frontal

Frontal

Figure 3. Cholinergic projections in the brain.

Nerve cells that release the neurotransmitter acetylcholine form the cholinergic system in the brain, which is divided into two parts: muscarinic (main focus of attention in memory) and nicotinic. The muscarinic projections are outlined in Figure 3, which represents a midline slice through the whole brain. Specific masses of nerve cells, or nuclei, in the deep part of the brain form the center of the muscarinic cholinergic system, and they use acetylcholine as their neurotransmitter. Degeneration of these cholinergic nerve cells deep in the brain leads to damage to the areas to which they project and are connected, namely, the hippocampus and frontal cortex. Naturally, memory loss is the result.

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