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.
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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Research by the authors is supported by the Canadian Institutes for Health Research.
The authors declare no competing financial interests.
A change in synapses that alters their ability to express plasticity.
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.
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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