Nicotinic Restoration of Prefrontal Cortex Physiology in Aged Monkeys

Aged monkeys, just like many older humans, have impairments in working memory. The prefrontal cortex is the most important brain area for this executive function, and networks of neurons in the prefrontal cortex must excite each other to sustain memories over a delay. Nicotinic receptors can be found on prefrontal cortex neurons near sites where these networks interconnect. Stimulation of nicotinic receptors by the neurotransmitter, acetylcholine, or by drugs that mimic acetylcholine, agonists such as nicotine, strengthens prefrontal network connections. Dr. Yang's project will examine whether these nicotinic receptor agonists can improve working memory in aged monkeys with weak prefrontal cortical network connectivity. Positive results will have immediate clinical significance, suggesting these drugs may also provide a useful treatment for cognitive deficits in the elderly.