Beta-adrenergic receptor activation during distinct patterns of stimulation critically modulates the PKA-dependence of LTP in the mouse hippocampus.
Activation of beta-adrenergic receptors (beta-ARs) enhances hippocampal memory consolidation and long-term potentiation (LTP), a likely mechanism for memory storage. One signaling pathway linked to beta-AR activation is the cAMP-PKA pathway. PKA is critical for the consolidation of hippocampal long-term memory and for the expression of some forms of long-lasting hippocampal LTP. How does beta-AR activation affect the PKA-dependence, and persistence, of LTP elicited by distinct stimulation frequencies? Here, we use in vitro electrophysiology to show that patterns of stimulation determine the temporal phase of LTP affected by beta-AR activation. In addition, only specific patterns of stimulation recruit PKA-dependent LTP following beta-AR activation. Impairments of PKA-dependent LTP maintenance generated by pharmacologic or genetic deficiency of PKA activity are also abolished by concurrent activation of beta-ARs. Taken together, our data show that, depending on patterns of synaptic stimulation, activation of beta-ARs can gate the PKA-dependence and persistence of synaptic plasticity. We suggest that this may allow neuromodulatory receptors to fine-tune neural information processing to meet the demands imposed by numerous synaptic activity profiles. This is a form of "metaplasticity" that could control the efficacy of consolidation of hippocampal long-term memories.
Gelinas
Jennifer N
JN
Department of Physiology, University of Alberta School of Medicine, Edmonton, Alberta T6G 2H7, Canada.
Tenorio
Gustavo
G
Lemon
Neal
N
Abel
Ted
T
Nguyen
Peter V
PV
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects*; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009415:Nerve Net / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D020710:RGS Proteins / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D002227:Carbazoles; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011758:Pyrroles; D020710:RGS Proteins; D011943:Receptors, Adrenergic, beta; C015482:protein kinase modulator; C057416:KT 5720; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol