University of Western Ontario - Electronic Thesis and Dissertation Repository

Location of Thesis Examination

Room 212A Medical Science Building

Degree

Doctor of Philosophy

Program

Physiology

Supervisor

Dr. Michael O. Poulter

Delay of Publication

1

Abstract

The piriform cortex (PC) is involved in olfactory sensory processing, associative learning tasks and is highly seizurogenic. Understanding how interneurons participate in these behaviours, especially their contribution in epileptogenic mechanisms, is hampered by an incomplete understanding of their functional and morphological diversity. The hypothesis in this work is that kindling-induced epilepsy alters the firing properties of PC interneuronal populations. Altered/impaired interneuronal firing could lead to abnormal processing in the PC and epileptogenesis. Therefore it was important to first identify and describe interneuronal morpho-functional properties in the unkindled brain and then to assess the electrophysiological parameters following kindling.

Based on interneuronal calcium-binding protein content, immunohistochemical analysis of PC showed that the four distinct interneuronal populations (calretinin, calbindin, parvalbumin, and parvalbumin/calbindin containing interneurons) had distinct layer localizations, preferred dendritic arborization patterns and specific innervations onto interneurons and pyramidal cells.

Whole cell patch-clamp recordings of PC interneuronal populations indicated a large heterogeneity of firing patterns that could be classified into five main patterns ranging from non-adapting very high frequency (NAvHF) to various degrees of spiking adaptation: adapting high frequency (AHF), adapting low frequency (ALF), strongly adapting low frequency (sALF), and weakly adapting low frequency (wALF). This high firing variability in the PC suggests that different interneuronal populations might have distinct functional means to control and regulate the olfactory network processing, memory coding and/or generation of oscillatory activities. However, after kindling, NAvHF and wALF firing patterns were absent. These changes were correlated to an increased K+ current in multipolar cells. This result was confirmed by quantitative real time polymerase chain reaction (QPCR) and immunohistochemistry studies indicating an increased expression of a voltage-gated potassium channel Kv1.6 after kindling. Thus, kindling-induced alteration of interneuronal firing properties, especially the absence of NAvHF firing behaviour, might reduce the efficacy of inhibition on the pyramidal cells leading to increased disinhibition and/or altered oscillatory activities in the PC.

Overall, this work provides a morpho-functional analysis of PC interneuronal populations indicating a high complexity of innervation and firing behaviours. It also shows for the first time that kindling induces alterations of interneuronal firing patterns that might be responsible for epileptogenesis in this area.