Noradrenaline is a stress-associated metaplastic signal at GABA synapses

Exposure to a stressor sensitizes behavioral and hormonal responses to future stressors. Stress-associated release of noradrenaline enhances the capacity of central synapses to exhibit plasticity (metaplasticity). We report noradrenaline-dependent metaplasticity at GABA synapses in the paraventricular nucleus of the hypothalamus in rat and mouse that control the hypothalamic-pituitary-adrenal axis. Previously, work indicates these GABA synapses become excitatory following acute stress. The current study finds that in vivo stress exposure is also required for these synapses to undergo activity-dependent long-term potentiation (LTP(GABA)). The activation of β-adrenergic receptors (β-ARs) during stress functionally upregulates metabotropic (mGluR1) glutamate receptors allowing for mGluR1-dependent LTP(GABA) during afferent bursts. LTP(GABA) is expressed postsynaptically and manifests as the emergence of new functional synapses. Our findings provide the first demonstration that noradrenaline release during an in vivo challenge alters information storage capacity at GABA synapses. These changes may contribute to neuroendocrine sensitization to stress.