title: Activation of β2-adrenoceptor enhances synaptic potentiation and behavioral memory via cAMP-PKA signaling in the medial prefrontal cortex of rats.
abstract: The prefrontal cortex (PFC) plays a critical role in cognitive functions, including working memory, attention regulation, behavioral inhibition, as well as memory storage. The functions of PFC are very sensitive to norepinephrine (NE), and even low levels of endogenously released NE exert a dramatic influence on the functioning of the PFC. Activation of β-adrenoceptors (β-ARs) facilitates synaptic potentiation and enhances memory in the hippocampus. However, little is known regarding these processes in the PFC. In the present study, we investigate the role of β2-AR in synaptic plasticity and behavioral memory. Our results show that β2-AR selective agonist clenbuterol facilitates spike-timing-dependent long-term potentiation (tLTP) under the physiological conditions with intact GABAergic inhibition, and such facilitation is prevented by co-application with the cAMP inhibitor Rp-cAMPS. Loading postsynaptic pyramidal cells with Rp-cAMPS, the PKA inhibitor PKI(5-24), or the G protein inhibitor GDP-β-S significantly decreases, but does not eliminate, the effect of clenbuterol. Clenbuterol suppresses the GABAergic transmission, while blocking GABAergic transmission by the GABA(A) receptor blocker partially mimics the effect of clenbuterol. In behavioral tests, a post-training infusion of clenbuterol into mPFC enhances 24-h trace fear memory. In summary, we observed that prefrontal cortical β2-AR activation by clenbuterol facilitates tLTP and enhances trace fear memory. The mechanism underlying tLTP facilitation involves stimulating postsynaptic cAMP-PKA signaling cascades and suppressing GABAergic circuit activities.
authors.affiliation: Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Hou-Cheng
authors.initials: HC
authors.lastname: Zhou
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: He
authors.forename: Feng
authors.initials: F
authors.lastname: Yi
authors.forename: Bao-Ming
authors.initials: BM
authors.lastname: Li
authors.forename: Xue-Han
authors.initials: XH
authors.lastname: Zhang
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D002976:Clenbuterol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D002976:Clenbuterol