Gamma oscillations drive the phase of theta waves in the hippocampus to enhance directed functional connectivity during memory processes

• Autores: Víctor José López Madrona
• Directores de la Tesis: Santiago Canals Gamoneda (dir. tes.)
• Lectura: En la Universidad Miguel Hernández de Elche ( España ) en 2019
• Idioma: inglés
• Tribunal Calificador de la Tesis: Salvador Sala Pla (presid.), Sandra Jurado Sánchez (secret.), Emilio Hernández García (voc.), Vicente Manuel Teruel Marti (voc.), Gertrudis Perea Parrilla (voc.)
• Programa de doctorado: Programa de Doctorado en Neurociencias por la Universidad Miguel Hernández de Elche
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• Resumen

  • One of the main features in brain activity is the presence of oscillations in electric recordings. These rhythms involve a broad range of frequencies, and the interaction between them is believed to play a key role in neuronal communication. In the hippocampus, a region quite related to the acquisition of new memories, theta and gamma waves are present along the whole structure, and its coupling is thought to route information flow. Nevertheless, neither the cellular mechanisms supporting this interaction, nor their behavioral functionality are well understood. Furthermore, it remains unclear how these ideas copes with the co-existence of multiple theta generators in the brain. In the present work, we have investigated the functional connectivity between different pathways converging in the hippocampus, which estimates, not only the intensity and frequency of the interaction, but also its directionality. Furthermore, we have analyzed possible nonlinear relationships that are not limited to oscillatory patterns, finding an increase of this activity in the dentate gyrus during the exploration of novel environments. While these tools offer a better characterization of the system, their interpretation in brain networks is not straightforward. Using computational simulations of neuronal data, we have studied the effect of nearby regions in the hippocampal interconnectivity, revealing that the entorhinal cortex wiring determines the information flow in the hippocampus. Finally, we have investigated the cross-frequency coupling (CFC) between theta and gamma oscillations, with a special attention in its relationship with the synchronization of the different theta generators. We found that CFC is stronger between oscillations within the same pathway and during epochs of high theta coherence among hippocampal layers. Interestingly, analysis of cross-frequency directionality indicated that the amplitude of gamma oscillations sets the phase of theta in all layer-specific theta-gamma pairs. These results suggest, contrary to an extended assumption, that layer- and band-specific gamma-oscillations coordinate theta rhythms. This mechanism may explain how anatomically distributed computations, organized in theta waves, can be bound together.