2nd Place in Health Professions - Laboratory Cellular Research at Denman Forum (Ohio State University)Symposium Distinction - 3rd Annual Neuroscience Undergraduate Research Forum (Ohio State University)Cognitive deficits in schizophrenia are thought to be caused, in part, by disrupted prefrontal cholinergic and glutamatergic transmission. Activation of the α7 nicotinic acetylcholine receptor (α7nAChR) has been shown to increase prefrontal glutamate as well as rescue failing performance in cognitive tasks in rodents and primates. Intra-accumbens stimulation with NMDA dose-dependently increases prefrontal acetylcholine, which in turn increases prefrontal glutamate via α7nAChR activity. Using NMDA stimulation as an assay to examine the potentiation of glutamate release as a function of the amount of acetylcholine released in the PFC, the potentiation profiles of two α7nAChR positive allosteric modulators (PAMs), AVL-3288 and PNU-120596, were assessed at varying levels of PAM and stimulation. Second-by-second measurements with a glutamate-sensitive microelectrode in the PFC in awake rats reveal that only an appropriate combination of the dose of NMDA and dose of PAM consistently potentiates prefrontal glutamate release. However, at other concentrations of NMDA and PAM, the effect on mesolimbic stimulation varied greatly from significant potentiation to a reduction of glutamate release. Furthermore, the potentiation profile for the type I and type II PAMs differed significantly, possibly due to differences in receptor desensitization in the presence of these two drugs. Overall, these results demonstrate the importance of dose of α7nAChR PAMs in modulating neurotransmitter systems, and PAMs as a potential therapeutic in treating cognitive deficits of schizophrenia as effects were dependent on activity of the orthosteric ligand.URO Summer FellowshipAcademic Enrichment GrantNo embargoAcademic Major: Neuroscienc
