Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pharmacology and Toxicology

Supervisor

Dr. Michael O. Poulter

Abstract

The integrity and stability of interneurons in a cortical network is essential for proper network function. Loss of interneuron synaptic stability and precise organization can lead to disruptions in the excitation/inhibition balance, a characteristic of epilepsy. This study aimed to identify alterations to the GABAergic interneuron network in the piriform cortex (PC: a cortical area believed to be involved in the development of seizures) after kindling-induced seizures. Immunohistochemistry was used to mark perineuronal nets (PNNs: structures in the extracellular matrix that provide synaptic stability and restrict reorganization of inhibitory interneurons) and interneuron nerve terminals in control and kindled tissue. Results indicated that the expression of fully formed PNNs was significantly decreased in kindled tissue and was correlated with an increased expression of matrix metalloproteinase 9 (MMP9: a protease known to degrade extracellular matrix structures). Inhibition of MMP9 by the anti- inflammatory drug, Doxycycline, provided an antiepileptic effect against amygdala kindling. Additionally, we observed a layer specific increase in interneuron release sites. These data show an important loss of interneuron stability in the PC after seizures. Our data suggests that under pathophysiological conditions interneuron wiring patterns are plastic and their synaptic rearrangement may contribute to the development of epilepsy.


Share

COinS