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Network properties of the mammalian circadian clock

Rohling, J.H.T.

Citation

Rohling, J. H. T. (2009, December 15). Network properties of the mammalian circadian clock. Retrieved from

https://hdl.handle.net/1887/14520

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/14520

Note: To cite this publication please use the final published version (if applicable).

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Network properties of the

mammalian circadian clock

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Network properties of the mammalian circadian clock

Proefschrift ter verkrijging van

de graad van Doctor aan de Universiteit Leiden,

op gezag van de Rector Magnificus Prof.mr. P.F. van der Heijden, volgens besluit van het College voor Promoties

te verdedigen op dinsdag 15 december 2009 klokke 11:15 uur

door

Johannes Hermanus Theodoor Rohling

geboren te Schoonebeek in 1970

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PROMOTIECOMMISSIE

Promotoren Prof. dr. H.A.G. Wijshoff Prof. dr. J.H. Meijer Co-promotor Dr. A.A. Wolters

Leden Prof. dr. G.D. Block (University of California, Los Angeles) Prof. dr. D.G.M. Beersma (Rijksuniversiteit Groningen) Prof. dr. S.M. Verduyn Lunel

Prof. dr. J.N. Kok Prof. dr. F.J. Peters

ISBN/EAN: 978-90-9024776-2

This work was supported by Netherlands Organization for Scientific Research (NWO), program grant nr 805.47.212 ‘From Molecule to Cell’.

This work was carried out in the ASCI graduate school.

ASCI dissertation series number 186.

Advanced School for Computing and Imaging

Printed by Universal Press, Veenendaal

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Table of contents

1 Introduction 1

1.1 The biological clock 1

1.2 Modelling and simulation 5

1.2.1 Mental models 6

1.2.2 Formal models 7

1.2.3 Models 8

1.2.4 Usability of models and simulations 9

1.3 More than the sum of parts 10

2 Mechanisms of the mammalian clock 13

2.1 Intracellular feedback loops 14

2.2 How to measure the rhythm of the clock 16 2.3 Networks of oscillating neurons 17 2.4 Properties of the clock: seasonality 18 2.5 Properties of the clock: jet lag 23 2.6 Properties of the clock: arrhythmicity 25 2.7 Intercellular communication: coupling between neurons 27

2.7.1 GABA 28

2.7.2 VIP 30

2.7.3 Gap junctions 33

2.7.4 Coupling in the SCN 34

2.8 Computer models and computer simulations of the clock 35 2.8.1 Interlude: Limit cycle oscillators 35

2.8.2 Two-oscillator models 39

2.8.3 Molecular models 43

2.8.4 Network models 47

2.9 Conclusions 50

3 Simulation of day length encoding 53

3.1 Introduction 53

3.2 Methods 55

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3.3 Results 59 3.3.1 From single cell to multiunit pattern 59 3.3.2 Mechanisms for photoperiodic encoding 63 3.3.3 Photoperiodic encoding by 2 populations 70

3.4 Discussion 74

3.4.1 Population patterns caused by distribution of neurons 74

3.4.2 Photoperiodic encoding 76

3.4.3 Bimodal distributions 81

4 Phase resetting caused by rapid shifts of small population of ventral SCN

neurons. 83

4.1 Introduction 83

4.2 Methods 84

4.2.1 In vitro electrophysiology 84

4.2.2 Analysis of in vitro electrophysiology 85

4.2.3 Subpopulation studies 86

4.2.4 Peak fitting 86

4.2.5 Simulation studies 87

4.3 Results 88

4.4 Discussion 95

5 Phase shifting of circadian pacemaker determined by SCN neuronal

network organization 99

5.1 Introduction 99

5.2 Methods 100

5.2.1 Ethics statement 100

5.2.2 Behavioral experiments 100

5.2.3 In vitro experiments 101

5.2.4 Data analysis 102

5.2.5 Simulations 103

5.3 Results and discussion 104

6 Asymmetrically coupled two oscillator model of circadian clock in the

SCN 117

6.1 Introduction 117

6.2 Mathematical model 123

6.3 Fitting the model 127

6.4 Results of the numerical simulations 129

6.5 Discussion 134

7 Summary, conclusions and future work 137

8 References 145

Nederlandse samenvatting 163

Glossary 171

List of publications 173

Acknowledgements 175

Curriculum vitae (in Dutch) 177

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