Systems Biology


Cellular and Systems Neurobiology

Mara Dierssen
María Martínez de Lagrán, Thomas Gener, Susanna Molas, Belén de Sancristóbal
Júlia Albaigès
Silvina Catuara, Marta Fructuoso, Linus Manubens


The Dierssen’s lab is interested on understanding cognition and behaviour as emergent properties of the neuronal networks and how genetic perturbation in mental disorders modify the way the brain integrates information to produce behaviour. The goal is to understanding how the neuronal architecture and connectivity constrain the mesoscopic network activity and influences the flow and storage of information in neuronal circuits. We aim to address an issue central to the theme of complexity in biological systems and specifically in the nervous system: the inferences that can be made from one level of integration to the next, along bottom-up (from microscopic to macroscopic) or top-down (from macroscopic to microscopic) axes. We have collected data on the mechanisms of information transfer in brain circuits from the single cell and molecular scale to the neuronal population level. A good model, which captures the relevance of this study, is cognitive disorder, because it refers to functional alterations that are accompanied by structural changes. Alterations in the architectural properties of the neurons are observed in most mental disorders and are assumed to be the cause of the cognitive disturbances. We focus mainly on intellectual disability and neuropsychiatric disorders, using a systems neuroscience approach that combines behavioural and neurobiological analyses in mice, with the results from cellular models. This systematic and wide-angled approach with different levels of description, has led us to build an integrated view of how the phenomic profiles correlate with cellular and molecular alterations in the neurons of these mouse models. This is a realistic stepping-stone towards unravelling the biological codes behind mental disorders. The value of our studies lies also in its translational angle. Based on our understanding of the genetic and molecular circuits disturbed in intellectual disability we have initiated a clinical trial in Down syndrome (de la Torre et al., 2013) and fragile X syndrome (FRAXA Foundation). Since our incorporation in the Systems Biology Programme in 2013, we have started to characterize the dynamics of multiple variables, which interact in a highly non-linear manner, as revealed by the richness of the collective behaviour of coupled neurons. The analysis of in silico neural networks captures the complex behaviour of these high-dimensional systems.

Research Projects

  • Brain operation in intellectual disability
    1. Neuronal network architecture and learning plasticity
      María Martínez de Lagrán – postdoctoral researcher (experimental)
      Silvina Catuara – PhD student (experimental)
      Thomas Gener– postdoctoral researcher
    2. Computational modelling of dynamical brain states in intellectual disability
      Belén de Sancristóbal – postdoctoral researcher (computational)
      Linus Manubens – PhD student (computational/experimental)
    3. Molecular constrains/biomarkers
      Laura Xicota – PhD student (experimental)
      Mireia Ortega– PhD student (experimental)
  • Computational tools for longitudinal phenotype recordings
    Jose Antonio Espinosa – PhD student (computational)
    Marcos Quevedo – PhD student (experimental)

Selected Publications

Pujol J, Del Hoyo L, Blanco-Hinojo L, de Sola S, Macià D, Martínez-Vilavella G, Amor M, Deus J, Rodríguez J, Farré M, Dierssen M, de la Torre R.
“Anomalous brain functional connectivity contributing to poor adaptive behavior in Down syndrome.”
Cortex, 64C:148-156. doi: 10.1016/j.cortex.2014.10.012 (2014).

Molas S, Gener T, Güell J, Martín M, Ballesteros-Yáñez I, Sanchez-Vives MV, Dierssen M.
“Hippocampal changes produced by overexpression of the human CHRNA5/A3/B4 gene cluster may underlie cognitive deficits rescued by nicotine in transgenic mice.”
Acta Neuropathol Commun, 2(1):147 (2014).

De la Torre R, De Sola S, Meritxell Pons Espinal, Duchon A, Martínez de Lagrán Cabredo M, Farré M, Fitó M, Benejam B, Langohr K, Rodriguez J, Pujadas M, Bizot JC, Cuenca A, Janel N, Catuara S, Covas MI, Blehaut H, Herault Y, Delabar JM, M. Dierssen.
“Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans.”
Molecular Nutrition & Food Research, 58(2)278-288.doi 10.1002/mnfr.201300325 (2014).

B. Mellström, Sahun I, A. Ruiz-Nuño, P. Murtra, R. Gomez-Villafuertes, M. Savignac, J.C. Oliveros, P. Gonzalez, A. Kastanauskaite, S. Knafo, M. Zhuo, A. Higuera-Matas, M.L. Errington, R. Maldonado, J. DeFelipe, J.G.R. Jefferys, T.V.P. Bliss, M. Dierssen, J.R. Naranjo.
“DREAM controls the on/off switch of specific activity-dependent transcription pathways.”
Molecular and Cellular Biology, 34(5)877-887.doi 10.1128/MCB.00360-13 (2014).

Sahun I, Marechal D, Lopes Pereira P, Nalesso V, Gruart A, Delgado Garcia JM, Antonarakis S, Dierssen M, Herault Y.
“Cognition and Hippocampal Plasticity in the Mouse Is Altered by Monosomy of a Genomic Region Implicated in Down Syndrome.”
Genetics,197(3)899-912. doi 10.1534/genetics.114.16524.1 (2014).