This paper summarizes a series of studies aimed at characterizing the effects of stress-related changes in synaptic inputs to the hypothalamic paraventricular nucleus (PVN). This structure generates an integrated physiological stress response by activating the hypothalamus-pituitary-adrenal (HPA) axis. Corticotropin-releasing hormone (CRH)-synthesizing parvocellular neuroendocrine neurons of the PVN play a key role in this process. They receive extensive excitatory and inhibitory innervation

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... veying information about interoceptive and exteroceptive stressful stimuli from a variety of sources within the brain. These synaptic inputs modulate the activity of PVN neurons, which regulates the amount of CRH released into the portal circulation of the anterior pituitary. It has been demonstrated that with either single or repeated stress sessions, the efficacy of excitatory and inhibitory synapses on parvocellular neuroendocrine neurons changes considerably, which may be related to repeated stress-induced sensitization of the HPA axis. The nature of these changes depends on the type of stress and its duration. Changes in synaptic inputs and the excitability of parvocellular neuroendocrine neurons are thought to be responsible for dysfunctions of the HPA axis observed in affective disorders. Assessing how this controlling function of PVN neurons is modulated in response to stress is crucial to our understanding of the pathophysiology of affective disorders.