Functional interactions of Infralimbic-Cerebellum pathways in cocaine-induced preference memory
- Autores: Julian Guarque Chabrera
- Directores de la Tesis: Marta Miquel Salgado-Araujo (dir. tes.), Kamran Khodakhah (codir. tes.)
- Lectura: En la Universitat Jaume I ( España ) en 2023
- Idioma: inglés
- Número de páginas: 287
- Tribunal Calificador de la Tesis: Juan Nacher (presid.), Fernando Martínez García (secret.), Barbara Sorg Ingermann (voc.), Alejandro Higuera Matas (voc.), Chris de Zeeuw de Zeeuw (voc.)
- Programa de doctorado: Programa de Doctorado en Ciencias Biomédicas y Salud por la Universidad Jaume I de Castellón
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
Reciprocal cerebellum-medial prefrontal cortex (mPFC) pathways provide a biological and functional substrate of their codependency on cognitive and motivational functions. Their dysfunction underlies the phenotypes of several neuropsychiatric disorders and may operate as a drug-addiction risk factor. Miquel's lab reported that infralimbic cortex (IL) and cerebellum exhibit drug-induced memory hallmark signatures. Moreover, a lesion in the vermal lobule LVIII (LVIII) of the cerebellum or an IL deactivation facilitated preference for cocaine-related cues, but simultaneous deactivations abolished it. Therefore, cerebellum-IL functional relationships might be compensatory. The VTA could be a relay on cerebellum-mPFC functions. Indeed, Khodakhah's lab could modulate reward-related behaviors by optogenetic manipulation of the cerebellar outputs targeting the VTA.
The present thesis investigates the cerebellum-IL hallmark signatures of drug-induced memories and their anatomical pathways.
To do so, we 1) assessed activity and perineuronal nets (PNNs) expression in the posterior cerebellum of IL-inactivated rats, 2) digested PNNs in LVIII at different time points of the learning process, and 3) created an anatomical map of the ascending and descending cerebellum-IL reciprocal pathways using tracing agents.
First, IL inactivation promoted cocaine-induced memory acquisition and upregulated cFos and vGluT2 activity around neurogranin+ Golgi interneurons and PNN expression in the posterior cerebellum. Second, LVIII PNNs enzymatic digestion disrupted short-term cocaine memory and facilitated reinstatement of the original cocaine memory by preventing the consolidation of extinction. Third, our anatomical maps show that LVIII via the interposed DCN might contact VTA and then contact IL, and IL might send projections to both interposed DCN and inferior olive and these areas that reach LVIII.
