TY - JOUR
T1 - β2-adrenergic receptor supports prolonged theta tetanus-induced LTP
AU - Qian, Hai
AU - Matt, Lucas
AU - Zhang, Mingxu
AU - Nguyen, Minh
AU - Patriarchi, Tommaso
AU - Koval, Olha M.
AU - Anderson, Mark E.
AU - He, Kaiwen
AU - Lee, Hey Kyoung
AU - Hell, Johannes W.
PY - 2012/5/15
Y1 - 2012/5/15
N2 - The Widespread noradrenergic innervations in the brain promotes arousal and learning by molecular mechanisms that remain largely undefined. Recent work shows that the β2-adrenergic receptor (β2AR) 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 β2AR 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 β1AR and β 2AR knockout (KO) mice, only β 2AR-selective stimulation with salbutamol supported this PTT-LTP in wild-type (WT) slices, whereas β1AR-selective stimulation with dobutamine (+ prazosin) did not. Furthermore, only the β 2AR-selective antagonist ICI-118551 and not the β1AR-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 2AR-S845 signaling pathway as a prominent regulator of synaptic plasticity.
AB - The Widespread noradrenergic innervations in the brain promotes arousal and learning by molecular mechanisms that remain largely undefined. Recent work shows that the β2-adrenergic receptor (β2AR) 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 β2AR 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 β1AR and β 2AR knockout (KO) mice, only β 2AR-selective stimulation with salbutamol supported this PTT-LTP in wild-type (WT) slices, whereas β1AR-selective stimulation with dobutamine (+ prazosin) did not. Furthermore, only the β 2AR-selective antagonist ICI-118551 and not the β1AR-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 2AR-S845 signaling pathway as a prominent regulator of synaptic plasticity.
KW - Beta-adrenergic signaling
KW - Postsynaptic signaling
KW - Protein kinase A
KW - α3-hy-droxy-5-methylisoxazole propionic acid receptors
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UR - http://www.scopus.com/inward/citedby.url?scp=84861142003&partnerID=8YFLogxK
U2 - 10.1152/jn.00374.2011
DO - 10.1152/jn.00374.2011
M3 - Article
C2 - 22338020
AN - SCOPUS:84861142003
SN - 0022-3077
VL - 107
SP - 2703
EP - 2712
JO - Journal of neurophysiology
JF - Journal of neurophysiology
IS - 10
ER -