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.
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.
|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|