Caracterització de les neurones glutamatèrgiques vestibulars en les respostes autònomes i aversives induïdes pel moviment

• Autores: Pablo Machuca Márquez
• Directores de la Tesis: Elisenda Sanz Iglesias (dir. tes.), Albert Quintana Romero (codir. tes.)
• Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2020
• Idioma: español
• ISBN: 9788449098642
• Tribunal Calificador de la Tesis: Marc Claret Carles (presid.), Raul Andero Galí (secret.), Sergi Simó Olivar (voc.)
• Programa de doctorado: Programa de Doctorado en Neurociencias por la Universidad Autónoma de Barcelona
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • Motion sickness (MS) is an autonomic physiological alteration occurring in individuals undergoing passive movement. It is currently believed that MS is encoded in the brain as a “toxic shock”, mirroring key aspects of toxic-induced nausea. Consistently, MS is characterized as an unpleasant feeling, accompanied by reduction in spontaneous ambulatory activity, appetite suppression, hypothermia and the establishment of conditioned taste aversion (CTA) –an association between a novel flavor and nausea-related gastrointestinal malaise–. It is widely accepted that MS develops with the occurrence of neural mismatches between the integrated input of motion-related sensory information and correlated past memory. In the brainstem, vestibular nuclei (VN) are classically associated with MS. Provocative motion activates VN neurons, recapitulating MS-related signs. However, the genetic identity of VN neurons mediating MS-related autonomic regulation and aversive learning, and their MS-relevant downstream projections remain largely unknown. In this PhD Thesis, we find that targeted inhibition of glutamatergic vestibular (VGLUT2VN) neurons during provocative motion prevents MS-like autonomic alterations and CTA response, revealing that VGLUT2VN neurons are necessary for MS establishment. Moreover, through cell type-specific neuronal tracing and optogenetic approaches, we identify a cholecystokinin-expressing, glutamatergic VN (CCKVN) subpopulation that projects to the parabrachial nucleus (PBN), dissecting a functionally-relevant circuit selectively controlling MS-related CTA. Together, these findings provide ground-breaking insights into MS neurobiological regulation, untangling key genetically-defined neural substrates and a vestibulo-parabrachial circuit.