Mechanisms of local synaptic effects of intracortical microstimulation in somatosensory cortex of mice and rats [Elektronische Ressource] / vorgelegt von Sergejus Butovas

Sergejus Butovas

Description

MECHANISMS OF LOCAL SYNAPTICEFFECTS OF INTRACORTICALMICROSTIMULATION INSOMATOSENSORY CORTEX OF MICE ANDRATSDissertationzur Erlangung des Grades eines Doktorsder Naturwissenschaften der Fakultät für Biologieundder Medizinischen Fakultätder Eberhard-Karls-Universität Tübingenvorgelegt vonSergejus Butovasaus Vilnius, LitauenTübingen, December 2006c Copyright 2006Date of defense: 22 May, 2007Dean Faculty of Biology: Prof. Dr. rer. nat. Friedrich SchöfflDean Faculty of Medicine: Prof. Dr. Ingo B. AutenriethFirst Reviewer: PD Dr. rer. nat. Cornelius SchwarzSecond Reviewer: Prof. Dr. rer. nat. Hanspeter MallotExamination Committee: PD Dr. rer. nat. Cornelius SchwarzProf. Dr. rer. nat. Peter ThierProf. Dr. rer. nat. Hanspeter MallotProf. Dr. rer. nat. Bernd AntkowiakPD Dr. Dipl.-Psych. Marina PavlovaiiI hereby declare that I have produced the work entitled: “Mechanisms oflocal synaptic effects of intracortical microstimulation in somatosensory cortexof mice and rats”, submitted for the award of a doctorate, on my own (withoutexternal help), have used only the sources and aids indicated and have markedpassages included from other works, whether verbatim or in content, as such. Iswear upon oath that these statements are true and that I have not concealedanything. I am aware that making a false declaration under oath is punishableby a term of imprisonment of up to three years or by a fine.

Sujets

• Gesundheit

Informations

• Publié par: eberhard_karls_universitat_tubingen
• Publié le: 01 janvier 2007
• Nombre de lectures: 23
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

MECHANISMS OF LOCAL SYNAPTIC EFFECTS OF INTRACORTICAL MICROSTIMULATION IN SOMATOSENSORY CORTEX OF MICE AND RATS

Dissertation zur Erlangung des Grades eines Doktors der Naturwissenschaften der Fakultät für Biologie und der Medizinischen Fakultät der Eberhard-Karls-Universität Tübingen vorgelegt von

Sergejus Butovas

aus Vilnius, Litauen

Tübingen, December 2006 c Copyright 2006

Date of defense: 22 May, 2007

Dean Faculty of Biology: Dean Faculty of Medicine:

First Reviewer: Second Reviewer:

Examination Committee:

Prof. Dr. rer. nat. Friedrich Schöffl Prof. Dr. Ingo B. Autenrieth

PD Dr. rer. nat. Cornelius Schwarz Prof. Dr. rer. nat. Hanspeter Mallot

PD Dr. rer. nat. Cornelius Schwarz Prof. Dr. rer. nat. Peter Thier Prof. Dr. rer. nat. Hanspeter Mallot Prof. Dr. rer. nat. Bernd Antkowiak PD Dr. Dipl.-Psych. Marina Pavlova

ii

I hereby declare that I have produced the work entitled: “Mechanisms of local synaptic effects of intracortical microstimulation in somatosensory cortex of mice and rats”, submitted for the award of a doctorate, on my own (without external help), have used only the sources and aids indicated and have marked passages included from other works, whether verbatim or in content, as such. I swear upon oath that these statements are true and that I have not concealed anything. I am aware that making a false declaration under oath is punishable by a term of imprisonment of up to three years or by a fine. I also declare that this version of the work does not differ in form or contents from the one submitted to the evaluation committee for review purposes.

Sergejus Butovas

Tübingen, December 2006.

iii

Dedicatory

This work is dedicated to

my mother, Svetlana Butova, who has been infinite source of love for me, to my family, wife Natalie and son Patrick, who have been always with me, and who have been supporting me over these years.

iv

Contents

Foreword 1. Introduction 2. Local synaptic effects of microstimulation in rat barrel cortex 3. Responses to microstimulation are determined by electrical synapses 4. Intrapontine communication mediated by the cerebellum 5. Intracortical microstimulation of barrel cortex in awake, head-restraint rats: assessment of detection threshold 6. Summary and conclusions References Appendices: A.1. Animal care statement A.2. Authorship contribution statement A.3. Acknowledgements

v

Page viii 1 4 6 9 12 16 18

24 25 26

List of

Figure 1:

Figure 2:

Figure 3:

Figure 4:

Figure 5:

Figure 6:

Figure 7:

Figures

Position of the multielectrode array in barrel cortex of rat.

Electrical gap junction

Diagram of basic neocortical circuitry

Compartmental map of pontine nuclei

Spatial distribution of labeled terminals in pontine nuclei

Schematic of experimental design

Neurometric and psychometric functions

vi

“The most exciting phrase to hear in science, the one that heralds new discoveries, is not ’Eureka!’ but ’That is funny’...”

Isaac Asimov, writer

“The important thing in science is not so much to obtain new facts as to discover new ways of thinking about them.”

vii

William Bragg, scientist

Foreword

The idea to stimulate neural tissue to restore impaired sensory functions origi- nates from inspiring studies of Brindley and Lewin, who have found that electri- cal stimulation of human occipital cortex produces simple visual percept (Brind- ley and Lewin, 1968). Today’s most successful application of electrical stimu- lation is the cochlear implant, a device that stimulates auditory nerve to treat deafness. However patients with lesions at higher stations of central nervous sys- tem cannot benefit from stimulation of peripheral nerves, leaving only opportu- nity to use neocortex for sensory signal introduction. As a result, the feasibility to use direct cortical stimulation to overcome injured pathways has acquired much of scientific attention. The main difficulty in this approach is to encode relevant percepts by using electrically induced neocortical activity. Despite re- cent evidence that cortical microstimulation is able to provide the substrate for a sensory percept, lack of knowledge about neuronal mechanisms underlying the “artificial” percepts delays clinical application of intracortical stimulation in neurologic patients. In this light, studies introduced in present thesis are focused on characterizing the neuronal and perceptual effects of intracortical stimulation. They are an attempt to relate percept to detailed spatio-temporal features of electrically evoked activity.

viii