SNAP-47 mediates somatic oxytocin dynamics in hypothalamic neurons

The neuropeptide oxytocin (OT) plays a crucial role in regulating homeostatic responses and complex behaviors, including social interaction. OT can be released from somatodendritic regions, enabling communication through retrograde, autocrine, and volume transmission. However, the mechanisms governing somatodendritic OT dynamics and their impact on neuronal function and behavior are not yet fully understood. Our study identifies SNAP-47, a member of the SNAP-25 protein family highly expressed in the soma of peptidergic neurons in the mouse hypothalamus, where it exhibits a close interaction with OT-containing compartments localized at the plasma membrane. Knocking down SNAP-47 diminishes the recruitment of OT to the plasma membrane in the cell body under both basal conditions and following neuronal stimulation. Reducing endogenous SNAP-47 expression in vivo results in altered spontaneous synaptic transmission in oxytocinergic neurons of the paraventricular nucleus (PVN) and decreases sociability, likely due to disrupted somatic trafficking. These findings provide new insights into the molecular mechanisms governing somatic OT dynamics, its influence on hypothalamic neuromodulation, and its role in OT-dependent behaviors such as social interaction.