E-Locus - Institutional Repository of the University of Crete

Home Collections School/Department School of Sciences and Engineering Department of Computer Science Post-graduate theses

Post-graduate theses

Current Record: 91 of 824

[Add to Basket]

Identifier

000438383

Title

Analysis of the activity patterns in focal cortical seizures using the 4-AP model

Alternative Title

Ανάλυση των μοτίβων δραστηριότητας στις εστιακές επιληπτικές κρίσεις χρησιμοποιώντας το 4-ΑΡ μοντέλο

Author

Ασβεστοπούλου, Θωμαΐς Ε.

Thesis advisor

Παπαδοπούλη, Μαρία

Reviewer

Τσαμαρδινός, Ιωάννης
Smirnakis, Stelios

Abstract

Epilepsy affects about 3% of the worldwide population. It is characterized by the repeated occurrence of highly synchronized and unprovoked bursts of neuronal activity, known as seizures. However, our understanding of how neurons interact to generate the abnormal network activity patterns that underlie ictogenesis is limited. It is important to understand what changes in the cortical circuit allow a highly-correlated firing state to emerge, evolve, and recur. To analyse the emergence and spread of focally initiated seizures, we used the 4-aminopyridine (4-AP) model, a well-established, reliable model of acute focal neocortical seizures. Using the calcium indicator GCaMP6s with in vivo two-photon cellular microscopy, we examined the activity profiles of individual neurons in layer 2/3 (L2/3) of the visual cortex during focal seizures induced by 4-AP injections in mice. We identified significant activity epochs in this context using two methodologies: a novel methodology based on the identification of the noise intervals of the fluorescence signal of each neuron, and another one based on the Recurrence Quantification Analysis, a powerful tool based on the topological analysis of the phase space of the underlying dynamics. Their results are consistent in terms of the presence of significant activity epochs and their duration. These approaches enable the identification of the onset of events of significant activity, aiming to dissect the mechanisms of seizure initiation and recruitment of neurons within the field of view. We also characterized the functional network connectivity using graph-theoretical metrics, such as normalized degree of connectivity, clustering coefficient, and weighted clustering coefficient. To capture the contribution and influence of a neuron to the connectivity of the network within a larger region, we introduced the affinity, a belief-propagation-based metric, that integrates the pairwise temporal correlation of the firing events of neurons in a sub-network. The analysis reveals the structure of the functional networks after the 4-AP injection, the significant increase of the temporal correlation of neurons, and the influence of neurons in the region close to the 4-AP injection. It comparatively examines the findings with other network architectures, including the functional network of the control (prior to the injection) as well as random graphs with well-defined structure.

Language

English

Subject

Focal epilepsy

Mouse

Single neuron resolution

Εστιακή επιληψία

Ποντίκι

Σε επίπεδο νεύρωνα

Issue date

2021-03-26

Collection