2009 Grants - Lawrence

Acetylcholine and Somatostatin Interactions in Alzheimer's Disease Models

John Joshua Lawrence, Ph.D.
The University of Montana
Missoula, Montana

2009 New Investigator Research Grant

Nerve cells in the brain are selectively vulnerable to cell death in the early stages of Alzheimer's disease. In a region of the brain called the hippocampus, nerve cells containing the neurotransmitter somatostatin are especially vulnerable. These cells receive signals from other cells that release the neurotransmitter acetylcholine, which binds to receptors on the somatostatin-containing cells and increases their activity. The acetylcholine-containing nerve cells are also especially vulnerable in early Alzheimer's disease. Indeed, many current therapies for early Alzheimer's disease are based on drugs to increase acetylcholine in the brain.

John Joshua Lawrence, Ph.D. and colleagues have proposed to study somatostatin-containing nerve cells in the hippocampus of mice that have been genetically altered to express Alzheimer-like pathology. The researchers plan to study how the activity of these cells is affected by signals from acetylcholine-containing cells, and what happens when those signals are lost, such as might occur when the acetylcholine-containing cells die. Dr. Lawrence's team also plans to examine whether selective vulnerability causes unusual activity in the hippocampus, such as what might occur during a seizure. These studies will advance our understanding of the consequences of selective nerve cell death in the early stages of Alzheimer's disease, and how those consequences may affect brain function.