Somatodendritic Vasopressin Release Couples Intrinsic Excitability To Population-Level Activity

The transition from single-neuron excitability to organized population firing is a fundamental feature of neural circuits, yet the mechanisms that govern this transition remain poorly understood. Magnocellular vasopressin (VP) and oxytocin neurons are intermingled within the hypothalamus, yet display strikingly different population dynamics, with VP output sustained by a distributed, largely asynchronous activity. Here, we identify a local mechanism by which somatodendritically released VP acts as a diffusible signal that converts an intrinsic excitability mechanism into spatially and temporally organized feedback across the VP population. Activity-dependent somatodendritic VP release recruited a rapid autocrine feedback that transiently potentiated the slow afterhyperpolarization (sAHP) through V1aR signaling which in turn strengthened spike-frequency adaptation and restrained firing. The same signal also acted in a diffusible, paracrine manner on neighboring VP neurons, producing distance- and time-dependent sAHP modulation, with rapid potentiation at short range and delayed inhibition at greater distances. Focal VP uncaging further revealed preferential engagement of somatic over dendritic signaling. Together, these findings show how a diffusible neuropeptide can convert an intrinsic excitability mechanism into spatially structured intercellular feedback, providing a candidate mechanism for sustaining distributed, asynchronous VP population output during prolonged homeostatic demand.