While studying cells in the cerebral cortex, Rodrigo Andrade, PhD, made an unusual discovery. The effects of the neurotransmitter, acetylcholine, depended on the level of activity of the cell. He became intrigued by this property because it provided a conditional mechanism for controlling cell function in the cerebral cortex. Since acetylcholine is required to maintain normal cognitive function, this mechanism could help explain how the loss of acetylcholine in the cerebral cortex leads to cognitive impairment. He was recently awarded nearly $1 million from the National Institutes of Health to continue his studies.
"Acetylcholine is very important in cognition and memory," said Dr. Andrade. "It regulates function in the cerebral cortex and serves as a neurotransmitter controlling many physiologic functions. Therefore, an acetylcholine deficit could make cells in the cortex function inappropriately in response to commands from other brain centers."
Dr. Andrade believes such a deficit could result in deterioration of cognitive abilities. "For example," he said, "if an animal is given atropine, a drug that blocks one class of acetylcholine receptors, it becomes highly disoriented. It may forget or not be able to use effectively what it has learned in the past, and may not be able to learn anything new at all."
This is a model for the kind of cognitive impairment that affects humans, particularly in aging when there is a loss of acetylcholine in cortex. "We want to understand what acetylcholine does at the cellular level in the cortex, so we can intervene and ameliorate cognitive deficits," Dr. Andrade said.
As an electrophysiologist, Dr. Andrade uses technology to aid in his research. Following is a confocal image of living neurons in cultured rat brain slices made visible by introducing into the cells the gene for a fluorescent protein from jellyfish. Studies on pyramidal cells of the cerebral cortex have allowed Dr. Andrade’s team to identify a novel ionic current which is regulated by acetylcholine in the brain.