Communication between pairs of neurons in the central nervous system typically involves classical “hard-wired” synaptic transmission, characterized by high temporal and spatial precision. Over the last two decades however, the repertoire of communication modalities in the brain has expanded, to include less-conventional forms characterized by a more diffuse, and less temporally precise transfer of information. These forms are best suited to mediate communication among entire neuronal populations, recognized now to be a fundamental process in the generation of complex behaviors. In response to an osmotic stressor, the hypothalamic paraventricular nucleus (PVN) generates a multimodal homeostatic response that involves an orchestrated neuroendocrine (systemic release of vasopressin) and autonomic (sympathetic outflow to the kidneys) components. The precise mechanisms that underlie inter-population crosstalk between these two distinct neuronal populations during an osmotic stressor, however, remain largely unknown. We identified a novel inter-population signaling modality that involves dendritic release of neuropeptides. We found that activity-dependent dendritic release of vasopressin from neurosecretory neurons in the PVN acted in a diffusible manner to increase the activity of distant (~100 µm) presympathetic neurons, resulting in turn in an integrated sympathoexcitatory population response (Son et al., Neuron 2013). This crosstalk was engaged by an NMDA-mediated increase in dendritic Ca2+, was influenced by vasopressin’s ability to diffuse in the extracellular space, and involved Ca2+-dependent activation of TRPM4/5 channels at the target neurons. Finally, using an in vivo hyperosmotic challenge, we provide direct evidence supporting a critical role for this inter-population crosstalk in the generation of a proper systemic sympathoexcitatory homeostatic response to a hyper osmotic challenge.