title: Activation of {beta}-adrenergic receptors facilitates heterosynaptic translation-dependent long-term potentiation.
abstract: Noradrenaline critically modulates the ability of synapses to undergo long-term plasticity on time scales extending well beyond fast synaptic transmission. Noradrenergic signalling through β-adrenergic receptors (β-ARs) enhances memory consolidation and can boost the longevity of long-term potentiation (LTP). Previous research has shown that stimulation of one synaptic pathway with a protocol that induces persistent, translation-dependent LTP can enable the induction of LTP by subthreshold stimulation at a second, independent synaptic pathway. This heterosynaptic facilitation depends on the regulation and synthesis of proteins. Recordings taken from area CA1 in mouse hippocampal slices showed that induction of β-AR-dependent LTP at one synaptic pathway (S1) can facilitate LTP at a second, independent pathway (S2) when low-frequency, subthreshold stimulation is applied after a 30 min delay. β-AR-dependent heterosynaptic facilitation requires protein synthesis as inhibition of mammalian target of rapamycin (mTOR), extracellular signal-regulated kinase (ERK), or translation, prevented homo- and heterosynaptic LTP. Shifting application of a translational repressor, emetine, to coincide with S2 stimulation did not block LTP. Heterosynaptic LTP was prevented in the presence of the cell-permeable cAMP-dependent protein kinase inhibitor, PKI. Conversely, the time window for inter-pathway transfer of heterosynaptic LTP was extended through inhibition of GluR2 endocytosis. Our data show that activation of β-ARs boosts the heterosynaptic expression of translation-dependent LTP. These results suggest that engagement of the noradrenergic system may extend the associative capacity of hippocampal synapses through facilitation of intersynaptic crosstalk.
authors: Centre for Neuroscience, University of Alberta School of Medicine, Medical Sciences Building, Edmonton, Canada.
authors: Steven A
authors: SA
authors: Connor
authors: Yu Tian
authors: YT
authors: Wang
authors: Peter V
authors: PV
authors: Nguyen
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D006624:Hippocampus; D017774:Long-Term Potentiation; D008810:Mice, Inbred C57BL; D011943:Receptors, Adrenergic, beta
chemical_list: D011943:Receptors, Adrenergic, beta