title: β2-Adrenergic receptor supports prolonged theta tetanus-induced LTP.
abstract: The widespread noradrenergic innervation in the brain promotes arousal and learning by molecular mechanisms that remain largely undefined. Recent work shows that the β(2)-adrenergic receptor (β(2)AR) is linked to the AMPA-type glutamate receptor subunit GluA1 via stargazin and PSD-95 (Joiner ML, Lise MF, Yuen EY, Kam AY, Zhang M, Hall DD, Malik ZA, Qian H, Chen Y, Ulrich JD, Burette AC, Weinberg RJ, Law PY, El-Husseini A, Yan Z, Hell JW. EMBO J 29: 482-495, 2010). We now demonstrate that the β(2)AR plays a prominent role in long-term potentiation (LTP) induced by a train of 900 stimuli at 5 Hz (prolonged theta-tetanus-LTP, or PTT-LTP) in the hippocampal CA1 region in mice, which requires simultaneous β-adrenergic stimulation. Although PTT-LTP was impaired in hippocampal slices from β(1)AR and β(2)AR knockout (KO) mice, only β(2)AR-selective stimulation with salbutamol supported this PTT-LTP in wild-type (WT) slices, whereas β(1)AR-selective stimulation with dobutamine (+ prazosin) did not. Furthermore, only the β(2)AR-selective antagonist ICI-118551 and not the β(1)AR-selective antagonist CGP-20712 inhibited PTT-LTP and phosphorylation of GluA1 on its PKA site S845 in WT slices. Our analysis of S845A knockin (KI) mice indicates that this phosphorylation is relevant for PTT-LTP. These results identify the β(2)AR-S845 signaling pathway as a prominent regulator of synaptic plasticity.
authors.affiliation: Dept. of Pharmacology, University of Iowa, Iowa City, IA, USA.
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.forename: Lucas
authors.initials: L
authors.lastname: Matt
authors.forename: Mingxu
authors.initials: M
authors.lastname: Zhang
authors.forename: Minh
authors.initials: M
authors.lastname: Nguyen
authors.forename: Tommaso
authors.initials: T
authors.lastname: Patriarchi
authors.forename: Olha M
authors.initials: OM
authors.lastname: Koval
authors.forename: Mark E
authors.initials: ME
authors.lastname: Anderson
authors.forename: Kaiwen
authors.initials: K
authors.lastname: He
authors.forename: Hey-Kyoung
authors.initials: HK
authors.lastname: Lee
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Hell
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D004280:Dobutamine / Q000494:pharmacology; D004558:Electric Stimulation; D007093:Imidazoles / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; C026777:ICI 118551; C049763:CGP 20712A