Role of intralaminar thalamic neurons during spike and wave discharges in a genetic rat model of absence epilepsy [Elektronische Ressource] / vorgelegt von Christoph Mittag

Christoph Mittag

Sujets

• Biologie

Informations

• Publié par: westfalische_wilhelms-universitat_munster
• Publié le: 01 janvier 2010
• Nombre de lectures: 5
• Langue: English
• Poids de l'ouvrage: 6 Mo

Extrait

Christoph Mittag



Role of intralaminar thalamic neurons during spike and wave
discharges in a genetic rat model of absence epilepsy


2010
Biologie




Dissertationsthema
Role of intralaminar thalamic neurons during spike and wave
discharges in a genetic rat model of absence epilepsy








Inaugural-Dissertation
zur Erlangung des Doktorgrades
der Naturwissenschaften im Fachbereich Biologie
der Mathematisch-Naturwissenschaftlichen Fakultät
der Westfälischen Wilhelms-Universität Münster












vorgelegt von
Christoph Mittag
aus Wiesbaden
-2010-






































____________________________________

Dekanin/Dekan: Prof. Dr. C. Klämbt

Erste Gutachterin/
Erster Gutachter: Prof. Dr. H.-C. Pape
Zweite Gutachterin/
Zweiter Gutachter: Prof. Dr. N. Sachser


Tag der mündlichen Prüfung(en): 27.09.2010....……………………......

Tag der Promotion: 22.10.2010.…………………………..

Contents


Table of contents

1. Introduction .................................................................................................. 5
1.1 Physiological properties of the thalamus .......................................................................5
1.2 The thalamocortical loop ...............................................................................................7
1.3 Absence epilepsy ..........................................................................................................9
1.3.1 The WAG/Rij model of absence epilepsy ...............................................................9
1.3.2 The putative role of thalamic networks to absence epilepsy .................................. 10
1.4 Objectives of the dissertation ...................................................................................... 11
2. Material and Methods ................................................................................ 13
2.1 Experimental setup ..................................................................................................... 13
2.2 Preparation and monitoring of animals ........................................................................ 14
2.3 Electrophysiological measurements ............................................................................ 16
2.3.1 Recording of ECoG .............................................................................................. 16
2.3.2 Unit recordings .................................................................................................... 16
2.3.3 Microiontophoresis .............................................................................................. 17
2.3.3.1 Fabrication of the electrode ........................................................................... 17
2.3.3.2 Microiontophoretic application ...................................................................... 19
2.3.4 Microstimulation .................................................................................................. 19
2.4 Data analysis ............................................................................................................... 21
2.4.1 Unit recordings .................................................................................................... 21
2.4.2 Microiontophoresis .............................................................................................. 22
2.4.3 Microstimulation .................................................................................................. 23
2.4.4 Statistics ............................................................................................................... 23
2.4.5 Histology ............................................................................................................. 24
3. Results ......................................................................................................... 26
3.1 Spike and Wave discharges ......................................................................................... 26
3.2 Unit recordings in the paracentral and centrolateral nucleus ........................................ 26
3.3 Microiontophoresis ..................................................................................................... 29
3.3.1 Effects of bicuculline on SWD-related firing ........................................................ 29
3.3.2 Effects of CGP on SWD-related firing ................................................................. 32
3.4 Microstimulation......................................................................................................... 35
3.4.1 Microstimulation in the paracentral nucleus ......................................................... 35
3.4.1.1 Stimulation at 7 Hz ........................................................................................ 35
3.4.1.2 Stimulation at 40 Hz ...................................................................................... 36
3.4.2 Microstimulation in the centrolateral nucleus ....................................................... 38
3.4.2.1 Stimulation at 7 Hz ........................................................................................ 38
3.4.2.2 Stimulation at 40 Hz ...................................................................................... 38 Contents

4. Discussion ................................................................................................... 40
4.1 Significance and limitation of WAG/Rij as a genetic model of human absence
epilepsy ..................................................................................................................... 40
4.2 Historical role of the intralaminar thalamic nuclei for absence epilepsy ..................... 41
4.2.1 Anatomical connection of the intralaminar thalamus ............................................ 42
4.3 Recent results shading new lights onto the role of intralaminar thalamic nuclei ......... 43
4.3.1 Unit recordings demonstrate a delayed recruitment of CL and PC during SWDs 44
4.3.2 Microiontophoretic experiments indicate a role of GABAergic inhibition ........... 47
4.3.3 Microstimulation experiments suggest a frequency-dependent recruitment ......... 51
4.4 Concluding remarks and outlook ................................................................................. 52
5. References ................................................................................................... 54
6. Zusammenfassung ...................................................................................... 60
7. Abbreviations ............................................................................................. 62
8. Danksagung ................................................................................................ 64
9. Tabellarischer Lebenslauf ......................................................................... 65


Introduction
1. Introduction

Rhythms are one central element of life. A well known example is the rhythm given by sleep
and wakefulness. For both states, the thalamus is of overall importance. It is a structure in the
diencephalon and consists of several nuclei. Each nucleus gets input from specific afferent
signal (e.g. visual or auditory sensory information) and transmits them to specific areas of the
cortex. In such a way, nearly all information we are aware of have to pass the thalamus (an
exception being olfactory information). Thus, the thalamus is in an ideal position to act as a
gateway, where incoming signals are either transferred to the cortex, or blocked. During
wakefulness the thalamus transfers incoming sensory signals, whereas during sleep, the flow
of information from the periphery to the cortex is interrupted within the thalamus (Jones,
1985; Sherman and Guillery, 2006). Because of its ability to control the flow of information
in dependence of sleep and wakefulness, the thalamus is often viewed as “the gate to
consciousness” (Pape et al., 2005).


1.1 Physiological properties of the thalamus

Early electrophysiological studies, using sharp intracellular microelectrodes, showed that
thalamic neurons fire in two different modes, depending on their membrane potential
(Jahnsen and Llinas, 1984a, b, c). During membrane potentials negative to -60 mV,
representing the hyperpolarized state, neurons generated a single burst of spikes, whereas
tonic repetitive firing was produced from membrane potentials positive to -60 mV,
representing the depolarized state (Fig. 1.1).

A B C



Fig. 1.1: Firing properties of a thalamic neuron. A) During hyperpolarization, the current pulse triggers an
all-or-none burst of spikes. B) The same current pulse causes a subthreshold depolarization when the membrane
potential was slightly depolarized. C) After further depolarization, the current