Advertisement

Altered Functional Connectivity in a Mouse Model of Fragile X Syndrome

  • Miguel Dasilva
  • Alvaro Navarro-Guzman
  • Luca Maiolo
  • Andres Ozaita
  • Maria V. Sanchez-Vives
Conference paper
Part of the Advances in Cognitive Neurodynamics book series (ICCN)

Abstract

We evaluated the integrity of the cortical network in the Fmr1 knockout mouse model of fragile X syndrome (FXS) by recording micro-electrocorticogram (ECoG) activity and measuring functional connectivity, alongside the degree of clustering (modularity) and integration capacity (path length). We found that functional connectivity is increased at both the short- and long-range levels, especially in prefrontal areas in the FXS model. This correlates with a decrement in the degree of cortical network clustering, together with an anomalously high information exchange capacity at high-frequency oscillatory bands. We conclude that the cognitive deficits manifested in FXS could be associated with the state of over-synchronization of the cortical network, which is more evident at high-frequency oscillatory bands and at frontal areas of the brain.

Keywords

Cortex Fragile X syndrome Functional connectivity Integration Segregation 

Notes

Acknowledgments

Funded by EU H2020 Research and Innovation Programme, Grant 720270 (HBP SGA1), BFU2014-52467-R (MINECO), BFU2015-68568-P (MINECO/FEDER, UE), FLAGERA-PCIN-2015-162-C02-01, FRAXA Research Foundation, and CERCA (Generalitat de Catalunya). We thank Ernesto Pereda de Pablo (Universidad de La Laguna) for his valuable suggestions for the analysis. We also thank Guglielmo Fortunato (CNR) for the collaboration on the design and fabrication of the electrodes.

References

  1. 1.
    Penagarikano, O., Mulle, J.G., Warren, S.T.: The pathophysiology of fragile x syndrome. Annu. Rev. Genomics Hum. Genet. 8, 109–129 (2007)CrossRefPubMedGoogle Scholar
  2. 2.
    Lozano, R., Rosero, C.A., Hagerman, R.J.: Fragile X spectrum disorders. Intractable Rare Dis. Res. 3, 134–146 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Gibson, J.R., Bartley, A.F., Hays, S.A., Huber, K.M.: Imbalance of neocortical excitation and inhibition and altered UP states reflect network hyperexcitability in the mouse model of fragile X syndrome. J. Neurophysiol. 5, 2615–2626 (2008)CrossRefGoogle Scholar
  4. 4.
    Compte, A., Reig, R., Descalzo, V.F., Harvey, M.A., Puccini, G.D., Sanchez-Vives, M.V.: Spontaneous high-frequency (10–80 Hz) oscillations during up states in the cerebral cortex in vitro. J. Neurosci. 28, 13828–13844 (2008)CrossRefPubMedGoogle Scholar
  5. 5.
    Wang, X.J.: Neurophysiological and computational principles of cortical rhythms in cognition. Physiol. Rev. 90, 1195–1268 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Sporns, O.: Structure and function of complex brain networks. Dialogues Clin. Neurosci. 15, 247–262 (2013)PubMedPubMedCentralGoogle Scholar
  7. 7.
    Gomis-Gonzalez, M., Busquets-Garcia, A., Matute, C., Maldonado, R., Mato, S., Ozaita, A.: Possible therapeutic doses of cannabinoid type 1 receptor antagonist reverses key alterations in fragile X syndrome mouse model. Genes (Basel). 7, 56 (2016)CrossRefGoogle Scholar
  8. 8.
    Bettinardi, R.G., Tort-Colet, N., Ruiz-Mejias, M., Sanchez-Vives, M.V., Deco, G.: Gradual emergence of spontaneous correlated brain activity during fading of general anesthesia in rats. NeuroImage. 114, 185–198 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Rubinov, M., Sporns, O.: Complex network measures of brain connectivity: uses and interpretations. NeuroImage. 52, 1059–1069 (2010)CrossRefPubMedGoogle Scholar
  10. 10.
    Ruiz-Mejias, M., Ciria-Suarez, L., Mattia, M., Sanchez-Vives, M.V.: Slow and fast rhythms generated in the cerebral cortex of the anesthetized mouse. J. Neurophysiol. 106, 2910–2921 (2011)CrossRefPubMedGoogle Scholar
  11. 11.
    Zhao, M., Zhou, C., Chen, Y., Hu, B., Wang, W.H.: Complexity versus modularity and heterogeneity in oscillatory networks: combining segregation and integration in neural systems. Phys. Rev. 82, 046225 (2010)Google Scholar
  12. 12.
    Van der Molen, M., Stam, C., Van der Molen, M.: Resting-state EEG oscillatory dynamics in fragile X syndrome: abnormal functional connectivity and brain network organization. PLoS One. 9, e88451 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Wang, J., Ethridge, L.E., Mosconi, M.W., White, S.P., Binder, D.K., Pedapati, E.V., Erickson, C.A., Byerly, M.J., Sweeney, J.A.: A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome. J. Neurodev. Disord. 9, 11 (2017)CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Testa-Silva, G., Loebel, A., Giugliano, M., de Kock, C.P., Mansvelder, H.D., Meredith, R.M.: Hyperconnectivity and slow synapses during early development of medial prefrontal cortex in a mouse model for mental retardation and autism. Cereb. Cortex. 22, 1333–1342 (2012)CrossRefPubMedGoogle Scholar
  15. 15.
    Bruno, J.L., Hosseini, S.M.H., Saggar, M., Quintin, E.M., Raman, M.M., Reiss, A.L.: Altered brain network segregation in fragile X syndrome revealed by structural connectomics. Cereb. Cortex. 27, 2249–2259 (2017)PubMedGoogle Scholar
  16. 16.
    Cea-Del Rio, C.A., Huntsman, M.M.: The contribution of inhibitory interneurons to circuit dysfunction in fragile X syndrome. Front. Cell. Neurosci. 8, 1–7 (2014)CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Miguel Dasilva
    • 1
  • Alvaro Navarro-Guzman
    • 1
  • Luca Maiolo
    • 2
  • Andres Ozaita
    • 3
  • Maria V. Sanchez-Vives
    • 1
    • 4
  1. 1.Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)BarcelonaSpain
  2. 2.Istituto per la Microelettronica e Microsistemi (CNR)RomeItaly
  3. 3.Universitat Pompeu Fabra (UPF)BarcelonaSpain
  4. 4.ICREABarcelonaSpain

Personalised recommendations