title: Activation of α7 nicotinic acetylcholine receptors facilitates long-term potentiation at the hippocampal-prefrontal cortex synapses in vivo.
abstract: Activation of α7 nAChRs has been shown to improve performance in a variety of nonclinical assays of cognitive function. The role of α7 nAChRs in cognitive processes is likely related to their role in modulating synaptic transmission and plasticity that have been reported in cell culture, brain slices, and intact animals. Here we report the effects of the α7 nAChR agonist FRM-17874 on synaptic plasticity within the hippocampal-medial prefrontal cortex pathway. Long-term potentiation (LTP) was generated by tetanic stimulation of CA1/subiculum region in urethane anesthetized male rats. Compared to saline controls, FRM-17874 significantly increased LTP (F(3,16)=10.39, p=0.0005) at doses of 0.3 and 1.0mg/kg but not with 3.0mg/kg, injected subcutaneously. Considering the physiological role of hippocampal LTP in mnemonic functions and memory formation, and the role of the hippocampal - prefrontal cortex pathway in working memory, the described neurophysiological effects could be a contributing mechanism underlying the cognitive effects of α7 nAChRs activation.
authors.affiliation: Translational Neuropharmacology, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Milan
authors.initials: M
authors.lastname: Stoiljkovic
authors.affiliation: Translational Neuropharmacology, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Kelley
authors.affiliation: Translational Neuropharmacology, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Dávid
authors.initials: D
authors.lastname: Nagy
authors.affiliation: FORUM Pharmaceuticals Inc., Waltham, MA 02451, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Hurst
authors.affiliation: Translational Neuropharmacology, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: mihaly.hajos@yale.edu.
authors.forename: Mihály
authors.initials: M
authors.lastname: Hajós
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018722:Nicotinic Agonists / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000502:physiology*; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013876:Thiophenes / Q000494:pharmacology*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists*
chemical_list: C000604696:7-fluoro-N-quinuclidin-3-yl)benzo(b)thiophene-2-carboxamide; D018722:Nicotinic Agonists; D011812:Quinuclidines; D013876:Thiophenes; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: Hippocampus; Long-term potentiation; Prefrontal cortex; α7 nACh receptors