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Discovery and Validation of Biomarkers Based on Computational Models of Normal and Pathological Hippocampal Rhythms

  • Péter ÉrdiEmail author
  • Tibin John
  • Tamás Kiss
  • Colin Lever
Chapter
Part of the Springer Series in Computational Neuroscience book series (NEUROSCI, volume 14)

Abstract

Quantitative systems pharmacology is an emerging field with the goal of offering new methodologies for drug discovery based on concepts that grew out of systems theory. Oscillation is a central topic of dynamical systems theory, and neural oscillations are related to both normal and pathological behavior. The role of abnormal neural oscillation in several dynamical diseases is briefly reviewed. Two special cases were investigated. The possible mechanisms of anxiolytic drugs on hippocampal electric patterns were analyzed by combined physiological and computational methods. A network of neuron populations that generates septo-hippocampal theta rhythm was modeled using a compartmental modeling technique. The effects of cellular and synaptic parameters were studied. Pyramidal hyperpolarization-activated (I h ) conductance and decay time constant of inhibitory post-synaptic current have significant effects on frequency. A biophysically realistic model of the electrical activity of the hippocampus, an early target of Alzheimer’s disease is also manipulated on a synaptic and cellular level to simulate biochemical effects of amyloid-\(\beta \) accumulation. This can help elucidate a mechanism of age-dependent theta oscillation changes in AD mouse models, reflecting changes in synchronous synaptic activity that could mediate oscillation-dependent memory deficiencies and serve as a biomarker for amyloid-\(\beta \) accumulation.

Key words:

Quantitative systems pharmacology Neural oscillation Dynamical diseases Theta rhythm Anxiety Alzheimer’s disease 

Notes

Acknowledgements

PE thanks the Henry Luce Foundation for letting him serve as a Henry R. Luce Professor. TJ thanks the Heyl Science Scholarship Fund and the Barry Goldwater Scholarship Program for their support in attending Kalamazoo College. TK is a full time employee and shareholder of Pfizer Inc and is on sabbatical leave from the Wigner Research Centre for Physics of the Hungarian Academy of Sciences. Some research reported in this paper was supported by a BBSRC New Investigator grant (BB/G01342X/1 and X/2) to CL.

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Péter Érdi
    • 1
    • 2
    Email author
  • Tibin John
    • 1
  • Tamás Kiss
    • 3
    • 2
  • Colin Lever
    • 4
  1. 1.Center for Complex Systems StudiesKalamazoo CollegeKalamazooUSA
  2. 2.Institute for Particle and Nuclear Physics, Wigner Research Centre for PhysicsHungarian Academy of SciencesBudapestHungary
  3. 3.Neuroscience Research Unit, Pfizer Global Research and DevelopmentCambridgeUSA
  4. 4.Department of PsychologyDurham UniversityDurhamUK

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