Unit:
Κατεύθυνση ΒιοπληροφορικήΠληροφορική
Author:
Sakavelis Athanasios
Supervisors info:
Ηλίας Μανωλάκος, Καθηγητής, Τμήμα Πληροφορικής & Τηλεπικοινωνιών, ΕΚΠΑ
Original Title:
Ανασκόπηση της Βιβλιογραφίας και Προσομοίωση Μοντέλων Νευρωνικών Κυκλωμάτων Σχετικών με τη Σχιζοφρένεια
Translated title:
Bibliographic Review and Simulation of Neuronal Circuit Models Relevant to Schizophrenia
Summary:
Schizophrenia is a very complex mental disorder of the central nervous system that affects almost 1% of the world’s population. It is characterized by an array of diverse symptoms, categorized as positive (such as hallucinations, delusions), negative (such as flat emotions, social withdrawal) and cognitive symptoms (such as learning and attention difficulties). The causes of the disease are believed to be a combination of genetic and environmental effects, but no causal genes have been identified so far. Although it has attracted the interest of the global research community, we are still lacking effective treatments for the disease. The molecular mechanisms underlying schizophrenia are still only partially understood and thus current antipsychotic drugs may present serious side effects and substantial response variability among patients. It is currently widely accepted that combination therapies targeting multiple receptors may be the answer to a more effective treatment of the various symptoms of the disease.
Over the last decade, the complexity of the disease and the availability of computational power has spurred a lot of interest in its mathematical modeling for the purpose of in silico investigations. There are several attempts to use systems of differential equations to capture the dynamical behavior and analyze the stability properties of closed-loop neuronal circuits involving different types of excitatory and inhibitory neurons, whose dysregulation is believed to be related to the disease symptoms.
This graduate diploma thesis first attempts a review of the contemporary literature regarding the main biological mechanisms involved in the pathogenesis of the disease. Then it focuses on presenting an overview of dynamical systems modeling approaches of neuronal circuits related to schizophrenia. Finally, it focuses on implementing in Matlab a specific neural circuit model of the prefrontal cortex related to the disease (developed by Dr.Tanaka) and explores its dynamical behavior when varying the model parameters. The main objective of this implementation was to develop insights and form the basis for a future multiscale modeling approach that will integrate neuronal circuit models of the underlying molecular level synaptic phenomena for a more complete study of schizophrenia-related mechanisms in silico.
Main subject category:
Technology - Computer science
Keywords:
Neural Circuits, Schizophrenia, Dynamical Systems, Mathematical Modeling, Biological Systems
