Lines of investigation
How are memories encoded, stored and retrieved in our brains?
Experience-dependent modulations of synaptic strength shape the functional structure of the brain, recruiting relevant networks in a particular context and supporting behavioural adaptation. Little is known, however, about how synapse dynamics are transformed into network dynamics. The work of our lab has demonstrated that brain circuits involved in learning and memory are functionally reorganized after local potentiation of synaptic transmission in the hippocampus. We are currently investigating the mechanisms underlying this network reorganization, focusing on short- and long-term synaptic plasticity and the excitatory/inhibitory balance in specific brain regions. In doing so, we study the mechanism that govern information routing in the complex network of parallel and highly distributed connections implemented in the brain. We use different animal models and combine functional magnetic resonance imaging (fMRI) with electrophysiological recordings, electric or optogenetic stimulations of targeted regions, and behavioural testing.
The same cellular mechanisms that mediate experience-dependent neuroplasticity and allow learning from, and react to, changes in the environment can also be activated by drugs of abuse. Human and animal studies indicate that the refractory nature of addiction results from drug-induced stimulation of reward-related learning networks. As a consequence, drug seeking behaviour becomes hard-wired in the addict’s brain. By applying the same multidisciplinary approach, we are investigating the functional reorganization of brain networks supporting addiction and relapse.
Representative Publications
- Mapping microglia and astrocyte activation in vivo using diffusion MRI Raquel Garcia-Hernandez, Antonio Cerdán Cerdá, Alejandro Trouve Carpena , Mark Drakesmith2, Kristin Koller, Derek K Jones , Santiago Canals , Silvia De Santis Sci Adv. 2022 8(21):eabq2923 https://doi.org/10.1126/sciadv.abq2923
- Different theta frameworks coexist in the rat hippocampus and are coordinated during memory-guided and novelty tasks López-Madrona VJ, Pérez-Montoyo E, Álvarez-Salvado E, Moratal D, Herreras O, Pereda E, Mirasso CR, Canals S eLife 2020 9:e57313 https://doi.org/10.7554/eLife.57313
- KAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain Lipinski M, Muñoz-Viana R, Del Blanco B, Marquez-Galera A, Medrano-Relinque J, Caramés JM, Szczepankiewicz AA, Fernandez-Albert J, Navarrón CM, Olivares R, Wilczyński GM, Canals S, Lopez-Atalaya JP, Barco A Nat Commun 2020 11(1):2588 https://doi.org/10.1038/s41467-020-16246-0
- Multishell diffusion imaging reveals sex-specific trajectories of early white matter degeneration in normal aging Toschi N, Gisbert RA, Passamonti L, Canals S, De Santis S Neurobiol Aging 2020 86:191 https://doi.org/10.1016/j.neurobiolaging.2019.11.014
- Microstructural White Matter Alterations in Men With Alcohol Use Disorder and Rats With Excessive Alcohol Consumption During Early Abstinence De Santis S, Bach P, Pérez-Cervera L, Cosa-Linan A, Weil G, Vollstädt-Klein S, Hermann D, Kiefer F, Kirsch P, Ciccocioppo R, Sommer WH, Canals S JAMA Psychiatry 2019 76(7):749 https://doi.org/10.1001/jamapsychiatry.2019.0318
- Finding influential nodes for integration in brain networks using optimal percolation theory Del Ferraro G, Moreno A, Min B, Morone F, Perez-Ramirez U, Peérez-Cervera L, Parra LC, Holodny A, Canals S, Makse HA Nat Commun 2018 9(1):2274 https://doi.org/10.1038/s41467-018-04718
- Increased Dosage of High-Affinity Kainate Receptor Gene grik4 Alters Synaptic Transmission and Reproduces Autism Spectrum Disorders Features Aller MI, Pecoraro V, Paternain AV, Canals S, Lerma J J Neurosci 2015 35(40):13619 https://doi.org/10.1523/JNEUROSCI.2217-15.2015
- Functional MRI of long-term potentiation: imaging network plasticity Alvarez-Salvado E, Pallares V, Moreno A, Canals S Philos Trans R Soc B-Biol Sci 2014 369 (1633) https://doi.org/10.1098/rstb.2013.0152