Dendritic Peptide Release Mediates Interpopulation Crosstalk between Neurosecretory and Preautonomic Networks

•Proof of a signaling modality mediating interpopulation crosstalk in the brain•Dendritic VP release from neurosecretory neurons stimulates autonomic neurons•Crosstalk involves Ca2+-mediated activation of a CAN channel in autonomic neurons•This crosstalk is involved in the generation of polymodal homeostatic responses

SummaryAlthough communication between neurons is considered a function of the synapse, neurons also release neurotransmitter from their dendrites. We found that dendritic transmitter release coordinates activity across distinct neuronal populations to generate integrative homeostatic responses. We show that activity-dependent vasopressin release from hypothalamic neuroendocrine neurons in the paraventricular nucleus stimulates neighboring (∼100 μm soma-to-soma) presympathetic neurons, resulting in a sympathoexcitatory population response. This interpopulation crosstalk was engaged by an NMDA-mediated increase in dendritic Ca2+, influenced by vasopressin’s ability to diffuse in the extracellular space, and involved activation of CAN channels at the target neurons. Furthermore, we demonstrate that this interpopulation crosstalk plays a pivotal role in the generation of a systemic, polymodal neurohumoral response to a hyperosmotic challenge. Because dendritic release is emerging as a widespread process, our results suggest that a similar mechanism could mediate interpopulation crosstalk in other brain systems, particularly those involved in generating complex behaviors.Video Abstract To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowHelp with MP4 filesOptionsDownload video (65247 K)