title: Noradrenaline is a stress-associated metaplastic signal at GABA synapses.
abstract: Exposure to a stressor sensitizes behavioral and hormonal responses to future stressors. Stress-associated release of noradrenaline enhances the capacity of central synapses to show plasticity (metaplasticity). We found noradrenaline-dependent metaplasticity at GABA synapses in the paraventricular nucleus of the hypothalamus in rat and mouse that controls the hypothalamic-pituitary-adrenal axis. In vivo stress exposure was required for these synapses to undergo activity-dependent long-term potentiation (LTPGABA). The activation of β-adrenergic receptors during stress functionally upregulated metabotropic glutamate receptor 1 (mGluR1), allowing for mGluR1-dependent LTPGABA during afferent bursts. LTPGABA was expressed postsynaptically and manifested as the emergence of new functional synapses. Our findings provide, to the best of our knowledge, the first demonstration that noradrenaline release during an in vivo challenge alters information storage capacity at GABA synapses. Because these GABA synapses become excitatory following acute stress, this metaplasticity may contribute to neuroendocrine sensitization to stress.
authors.affiliation: Hotchkiss Brain Institute, Calgary, Alberta, Canada.
authors.forename: Wataru
authors.initials: W
authors.lastname: Inoue
authors.forename: Dinara V
authors.initials: DV
authors.lastname: Baimoukhametova
authors.forename: Tamás
authors.initials: T
authors.lastname: Füzesi
authors.forename: Jaclyn I
authors.initials: JI
authors.lastname: Wamsteeker Cusulin
authors.forename: Kathrin
authors.initials: K
authors.lastname: Koblinger
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Whelan
authors.forename: Quentin J
authors.initials: QJ
authors.lastname: Pittman
authors.forename: Jaideep S
authors.initials: JS
authors.lastname: Bains
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000075402:Channelrhodopsins; D002614:Chelating Agents / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D008027:Light; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013315:Stress, Psychological / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000075402:Channelrhodopsins; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D008164:Luminescent Proteins; D018377:Neurotransmitter Agents; D018019:Receptors, Corticotropin-Releasing Hormone; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D005680:gamma-Aminobutyric Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D009638:Norepinephrine
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