Somatodendritic oxytocin release: dynamics and molecular machinery

• Autores: Beatriz Aznar Escolano
• Directores de la Tesis: Sandra Jurado Sánchez (dir. tes.)
• Lectura: En la Universidad Miguel Hernández de Elche ( España ) en 2025
• Idioma: español
• Tribunal Calificador de la Tesis: Amparo Gil Gómez (presid.), Luis Miguel Gutiérrez Pérez (secret.), Virginia González Velez (voc.)
• Programa de doctorado: Programa de Doctorado en Neurociencias por la Universidad Miguel Hernández de Elche
• Materias:
  • Ciencias de la vida
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• Resumen

  • Oxytocin (OT) is a neuropeptide hormone that plays a key role in the regulation of social behaviors. Primarily synthesized in the hypothalamus, OT production is centered in the paraventricular (PVN) and supraoptic (SON) nuclei. From there, OT is released into the bloodstream, where it supports functions like childbirth and the milk ejection reflex, and into the brain, where it influences social behaviors, including attachment, maternal care, and aggression. Dysregulation of the oxytocinergic system has been associated with impairments in social behaviors, as seen in autism spectrum disorder (ASD).

    OT is stored within Dense Core Vesicles (DCVs), whose release properties remain less understood compared to Synaptic Vesicles (SVs). To address this knowledge gap, the primary aims of this thesis were to characterize the dynamic properties of OT release and to identify the molecular machinery involved.

    To achieve these objectives, we used live-cell microscopy and secretion assays in primary hypothalamic cultures to analyze OT-containing compartments' dynamics under both basal and stimulated conditions, with and without extracellular calcium.

    A detailed analysis of SNARE protein expression in hypothalamic slices and cultures identified SNAP-47 as a key somatodendritic SNARE protein. This non-canonical SNARE was closely associated with OT-membrane patches, positioning it to play a significant role in OT dynamics and release during both basal and stimulated states. Furthermore, the elimination of SNAP-47 in the PVN reduced sociability in mice, suggesting that alterations in somatodendritic OT dynamics may affect basic aspects of social behavior.

    In summary, our findings reveal that OT vesicles represent a heterogeneous population regulated by a unique SNARE complex involving SNAP-47, which contributes to both basal and activity-dependent mobilization of OT in hypothalamic neurons, potentially impacting social behavior.