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Stress-related synaptic plasticity in the hypothalamus

Nature Reviews Neuroscience volume 16, pages 377–388 (2015)Cite this article

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Key Points

  • Glutamate and GABAergic synapses on stress-responsive neuroendocrine cells in the paraventricular nucleus of the hypothalamus (PVN) exhibit different forms of plasticity in response to acute stress.

  • Following acute stress, glutamatergic synapses switch to a multivesicular release mode in response to bursts of presynaptic activity.

  • GABAergic synapses become conditionally excitatory following stress. This is due to a collapse of transmembrane chloride gradients.

  • GABAergic synapses can exhibit potentiation or depression after stress. The polarity is dictated by the amount of time that has elapsed since the stress.

  • Endocannabinoid signalling is highly labile in the PVN. It is enhanced by acute stress, collapses in response to repeated homotypic stress, and is reset by a novel experience after the repeated stress.

Abstract

Stress necessitates an immediate engagement of multiple neural and endocrine systems. However, exposure to a single stressor causes adaptive changes that modify responses to subsequent stressors. Recent studies examining synapses onto neuroendocrine cells in the paraventricular nucleus of the hypothalamus demonstrate that stressful experiences leave indelible marks that alter the ability of these synapses to undergo plasticity. These adaptations include a unique form of metaplasticity at glutamatergic synapses, bidirectional changes in endocannabinoid signalling and bidirectional changes in strength at GABAergic synapses that rely on distinct temporal windows following stress. This rich repertoire of plasticity is likely to represent an important building block for dynamic, experience-dependent modulation of neuroendocrine stress adaptation.

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Figure 1: Stress and functional connectivity.
Figure 2: Major direct and indirect CNS connections to the PVN.
Figure 3: Glutamatergic synapses — function and plasticity.
Figure 4: GABAergic synapses — function and plasticity.

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Acknowledgements

Research by the authors is supported by the Canadian Institutes for Health Research.

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Author notes

  1. Jaclyn I. Wamsteeker Cusulin

    Present address: Present address: Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland.,

  2. Wataru Inoue

    Present address: Present address: Robarts Research Institute, Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, 1151 Richmond Street North, London, Ontario N6A 5B7, Canada.,

Authors and Affiliations

  1. Hotchkiss Brain Institute and the Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, T2N 4N1, Alberta, Canada

    Jaideep S. Bains, Jaclyn I. Wamsteeker Cusulin & Wataru Inoue

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  1. Jaideep S. Bains
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Correspondence to Jaideep S. Bains.

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PowerPoint slides

Glossary

Metaplasticity

A change in synapses that alters their ability to express plasticity.

Kairoplasticity

Derived from the Greek 'kairos', meaning the opportune or correct moment, it refers to observations that different forms of metaplasticity following stress that can be induced only during specific and distinct temporal windows.

Spillover

When a neurotransmitter from one synapse acts at a neighbouring synapse; for example, when glutamate escapes the synaptic cleft and acts on nearby synapses.

Heterosynaptic modulation

When one transmitter system (for example, glutamate) affects a neighbouring but different system (for example, GABA).

Homotypic stress

Repeated administration of the same stressor to an animal.

K-Cl co-transporter 2

(KCC2). A transmembrane potassium–chloride co-transporter that extrudes chloride and maintains the driving force for chloride influx into cells upon the opening of GABAA receptors.

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Bains, J., Cusulin, J. & Inoue, W. Stress-related synaptic plasticity in the hypothalamus. Nat Rev Neurosci 16, 377–388 (2015). https://doi.org/10.1038/nrn3881

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