A decline in cognitive functions such as attention, memory, and decision making is observed in a series of neurodegenerative conditions and mental illnesses. Cholinergic drugs (acetylcholine agonists and acetylcholinesterase inhibitors) can reverse these symptoms. Despite the known effectiveness of cholinergic drugs in improving cognitive function, the neuronal mechanisms of action in cortical areas involved in these processes, such as the prefrontal cortex are poorly understood. This project will investigate the effects of cholinergic drugs on prefrontal cortical activity during the execution of cognitive task and the effects of stimulation of the Nucleus Basalis, the main source of endogenous cortical acetylcholine. Neurophysiological recordings will be performed by a chronically implanted array of microelectrodes over the prefrontal cortex during the systemic administration of cholinergic agents and deep brain stimulation in a non- human primate model. The experiments will allow us to understand the effects of cholinergic agents in the prefrontal cortex associated with cognitive performance. They will also evaluate the relative effectiveness of drug administration compared to deep brain stimulation. Our research will also provide a primate model for the evaluation of new types of drugs that can potentially improve cognitive rehabilitation following injury or illness.

Public Health Relevance

Diminished levels of the neurotransmitter acetylcholine in the brain have been implicated in cognitive impairments associated with ageing, dementia, and mental illnesses. The proposed research will determine the effects of acetylcholine levels in a brain area critical for higher cognitive functions, the prefrontal cortex, and evaluate the effectiveness of interventions for the improvement of cognitive functions, using an animal model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH097695-05
Application #
9269276
Study Section
Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
Program Officer
Rossi, Andrew
Project Start
2013-09-01
Project End
2018-04-30
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
5
Fiscal Year
2017
Total Cost
$345,663
Indirect Cost
$89,811
Name
Wake Forest University Health Sciences
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Poddar, Indrani; Callahan, Patrick M; Hernandez, Caterina M et al. (2018) Tropisetron enhances recognition memory in rats chronically treated with risperidone or quetiapine. Biochem Pharmacol 151:180-187
Liu, Ruifeng; Crawford, Jonathan; Callahan, Patrick M et al. (2017) Intermittent Stimulation of the Nucleus Basalis of Meynert Improves Working Memory in Adult Monkeys. Curr Biol 27:2640-2646.e4