Photoperiodic encoding by the neuronal network of the suprachiasmatic nucleus Leest, H.T. van der

Photoperiodic encoding by the neuronal network of the suprachiasmatic nucleus

Leest, H.T. van der

Citation

Leest, H. T. van der. (2010, November 3). Photoperiodic encoding by the

https://hdl.handle.net/1887/16100

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P HOTOPERIODIC E NCODING BY THE

N ^EURONAL N ETWORK OF THE

S UPRACHIASMATIC N ^UCLEUS

Henk Tjebbe van der Leest

P HOTOPERIODIC E NCODING BY THE

N ^EURONAL N ETWORK OF THE

S UPRACHIASMATIC N ^UCLEUS

Proefschrift ter verkrijging van

de graad van Doctor aan de Universiteit Leiden

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

te verdedigen op woensdag 3 november 2010 klokke 13.45 uur

door

Henk Tjebbe van der Leest geboren te Rotterdam

in 1979

Promotiecommissie Promotor:

Prof. dr. J.H. Meijer Overige leden:

Prof. H.D. Piggins (University of Manchester)

Prof. dr. B van der Horst (Erasmus Medical Center) Dr. R. Hut (University of Groningen)

The research presented in this thesis was performed at the Leiden University Medical Center, group Neurophysiology, department of Molecular Cell Biology.

This work was supported by program grant "From Molecule to Cell"

by the Netherlands Organization for Scientific Research (NWO), grant number 805.47.212 and by "Entrainment of the circadian clock"

EUCLOCK program of the European Union.

T ^{ABLE OF} C ^ONTENTS

C

1 2

Introduction

Circadian Rhythms ... 2

Discovery of the suprachiasmatic nucleus ... 4

SCN rhythms are autonomous ... 6

Circadian rhythms are generated by a molecular clock ... 7

The SCN is a pacemaker... 10

SCN drives rhythms through electrical activity ... 11

Output of the SCN is electrical and humoral ... 13

Anatomy of the circadian visual system ... 14

Photo receptors in the retina ... 14

Innervation of the SCN ... 16

Retinohypothalamic tract ... 17

Neurotransmitters of the RHT ... 17

Geniculohypothalamic tract ... 19

Anatomy of the suprachiasmatic nucleus ... 20

Entrainment by light ... 21

The SCN as a Neuronal Network ... 23

Introduction to research questions ... 26

C

2 30

Introduction ... 32

Methods ... 34

Results ... 38

Discussion ... 40

Supplemental Data ... 47

C

3 48

Introduction ... 50

Methods ... 52

Electrophysiological Recording ... 52

Data Analysis ... 52

Results ... 54

Phase Differences between SCN Regions ... 54

Phase and Shape Differences within SCN Regions ... 55

Neuronal Activity Patterns of Single Units ... 57

Simulations of Neuronal Discharge Patterns ... 58

Phase Differences Contribute to Photoperiod Adaptation ... 59

Discussion ... 61

Single Unit Discharge Pattern ... 63

Phase Differences Contribute to Day Length Adaptation ... 66

C

4 70

Results and Discussion ... 72

In vivo Multiunit Recordings ... 72

In vitro Multiunit and Subpopulation Recordings ... 74

Circadian Single-Unit Activity Patterns ... 78

Experimental Procedures ... 83

C

5 90

Introduction ... 92

Results and Discussion ... 94

Materials and Methods ... 104

Supplemental Data - Simulations ... 107

C

6 110

Time of preparation does not influence MUA in vitro ... 111

Phase heterogeneity of SCN neurons ... 112

Photoperiodic Encoding ... 114

Molecular versus Electrical oscillations in the SCN ... 116

Phase shifting responses in long and short photoperiod ... 117

Limit cycle oscillators ... 119

Perspectives ... 121

Mechanisms for Synchronization ... 121

Role of synchronization in the aging SCN ... 124

SCN network rescues molecular clock deficits ... 126

R

128

S

156

N

S

162

G

170

L

P

172

A

174

C

V

176