Role of Central Vasopressin in the Generation of Multimodal Homeostatic Responses

Maintenance of bodily homeostasis involves orchestrated activities between hypothalamic autonomic and neuroendocrine neuronal networks. Importantly, an imbalanced interaction between these networks results in maladaptive responses characteristic of disease conditions, including stress, hypertension, and diabetes. Still, the precise signaling mechanisms underlying interpopulation crosstalk in the hypothalamus remain controversial. Neuropeptides are increasingly recognized as unique signals involved in information processing in the brain. Differently from classical fast-acting neurotransmitters, neuropeptides are abundantly found in dendrites, their release is not targeted at synaptic postsynaptic sites, and given their relatively long half-lives, they can diffuse in the extracellular space (ECS) to act on distant targets. The advent of recent technological approaches that allow for precise spatial and temporal activation of identified neuronal populations has enabled the study of precise signaling mechanisms that mediate interpopulation crosstalk. The multidisciplinary use of such approaches demonstrated that dendritic release of vasopressin mediates crosstalk between magnocellular neurosecretory and presympathetic neurons in the PVN. This crosstalk ranges from the cell-to-cell to the entire interpopulation level, playing in turn a critical role in the generation of orchestrated neurosecretory and sympathetic homeostatic responses.