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Cited by 94Neuroscience and Neuropharmacology ResearchStress Responses and CortisolMemory and Neural Mechanisms

Noradrenaline is a stress-associated metaplastic signal at GABA synapses

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Inoue, Wataru, Baimoukhametova, Dinara V, Füzesi, Tamás, Cusulin, Jaclyn I Wamsteeker, Koblinger, Kathrin, Whelan, Patrick J, Pittman, Quentin J, Bains, Jaideep S·2013·Nature Neuroscience
DOI 10.1038/nn.3373PMC PMC3984240
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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.

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  • This effect is necessary for attenuation of inhibiting GABA action and disinhibition of HPA axis.

    “This effect is necessary for the attenuation of the inhibiting GABA action and the disinhibition of the HPA axis [113].”

    From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [113]

    The Discussion (page unavailable) describes a shift from inhibitory to conditionally excitatory GABA action after stress and suggests that this may contribute to HPA-axis sensitization. It does not establish that the effect is necessary for HPA-axis disinhibition; that necessity claim overstates the paper. (LLM, conf=0.84)

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  • The GABAergic synapse on CRH neurons becomes excitatory immediately after onset of stress, due to disruption of chloride gradient induced by norepinephrine action.

    “For example, immediately after the onset of stress the GABA synapse on CRH neurons becomes excitatory, due to the disruption of the chloride gradient induced by norepinephrine action.”

    From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [113]

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Authors
Inoue, W., Baimoukhametova, D. V., Füzesi, T., Cusulin, J. I. W., Koblinger, K., Whelan, P. J., Pittman, Q. J., & Bains, J. S.
Affiliations
  • Hotchkiss Brain Institute (CA)
  • University of Calgary (CA)
Corresponding author
Bains, Jaideep S
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2013-04-07
Volume
16
Issue
5
Pages
605-612
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/nn.3373
PMC
PMC3984240
OpenAlex
W2066183427
Cited by
94
References
4
Citations by year
2025: 4 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 2 · 2020: 8 · 2019: 6 · 2018: 10 · 2017: 7 · 2016: 10 · 2015: 10 · 2014: 17 · 2013: 7
FWCI
5.93
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
Canadian Institutes of Health Research (86501_2)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
norepinephrine, metaplasticity, GABAergic synapses, paraventricular nucleus, metabotropic glutamate receptor 1, long-term potentiation, beta-adrenergic receptors, stress, hypothalamic-pituitary-adrenal axis, synaptic plasticity
MeSH terms
Channelrhodopsins, Animals, Animals, Newborn, Chelating Agents, Disease Models, Animal, Enzyme Inhibitors, gamma-Aminobutyric Acid, Hypothalamus, Light, Luminescent Proteins, Male, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity, Norepinephrine, Stress, Psychological, Synapses, Signal Transduction, Rats, Sprague-Dawley, Cyclic AMP-Dependent Protein Kinases, Receptors, Corticotropin-Releasing Hormone, Receptors, Metabotropic Glutamate, Neurotransmitter Agents, Mice, Rats, Inhibitory Postsynaptic Potentials, In Vitro Techniques

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