circadian clock in mammals
DESCRIPTION
AACIMP 2011 Summer School. Neuroscience Stream. Lecture by Nikolai Kononenko.TRANSCRIPT
![Page 1: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/1.jpg)
From 25 1
Circadian Clock in Mammals
Nikolai I. Kononenko
Department of General Physiology of Nervous System, Bogomoletz Institute of Physiology,
Kiev, Ukraine
![Page 2: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/2.jpg)
From 25 2
INTRODUCTION
As a consequence of the Earth’s rotation about its axis approximately every 24 hours, most organisms on our planet are subjected to fluctuations of light and temperature. A diverse range of species, from cyanobacteria to humans, developed endogenous biological clocks that allow for the anticipation of these daily variations. Thus, our internal physiology and function are fundamentally intertwined with this geophysical cycle.
![Page 3: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/3.jpg)
From 25 3
The mammalian circadian timing system
Hypothalamus
The paired suprachiasmatic nuclei (SCN) of the hypothalamus is the primary biological clock regulating circadian rhythms in mammals.
It has been show by lesion of these nuclei, destroying circadian behavior, with subsequent its restoration by implantation of SCN
from donor animal.
Retino-hypothalamictract
![Page 4: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/4.jpg)
From 25 4
Coronal and horizontal slices of suprachiasmatic nuclei
Retino-hypothalamicglutamate tract
~ 700
![Page 5: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/5.jpg)
From 25 5
Suprachiasmatic nuclei of the mouse
1 mm
![Page 6: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/6.jpg)
From 25 6
SCN neurons of the mouse at infrared differential interference contrast microscopy
100 m
![Page 7: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/7.jpg)
From 25 7
Multiple-unit activity (MUA) from the rat SCN in vitro.
from ~100 SCN neurons
![Page 8: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/8.jpg)
From 25 8
1. The paired suprachiasmatic nuclei (SCN) of the hypothalamus is the primary biological clock regulating
circadian rhythms in mammals
![Page 9: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/9.jpg)
From 25 9
Multielectrode array dish (MED)
0
6
Hz
0 1 2 3 4 5(Days)
1 min
1 mm
![Page 10: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/10.jpg)
From 25 10
Activity of dispersed SCN neurons in MED and MUA of SCN in slice preparation
Firi
ng r
ate
(Hz)
![Page 11: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/11.jpg)
From 25 11
Individual SCN neurons express self-sustained circadian oscillations. As a result of internal coupling, the SCN generates a coherent output signal
![Page 12: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/12.jpg)
From 25 12
Three main components of clock:a) oscillator, b) gear, and c) hands or digitals
![Page 13: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/13.jpg)
From 25 13
Circadian-clockcore
Messenger
Membrane target
0
6
Hz
![Page 14: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/14.jpg)
From 25 14
Minimal mammalian circadian clockwork model (circadian oscillator)
From Scheper et al., J Neurosci 1999
The delay and nonlinearity in the protein production and the cooperativity in the negative feedback were found to be necessary
and sufficient to generate robust circadian oscillations
Period
Period
Period*
![Page 15: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/15.jpg)
From 25 15
Temperature compensation
The effect of changes in temperature on the rate of most biochemical reactions is measured by a Q10 value, which is defined as the ratio of the rate of a given process at one temperature to the rate at a temperature 10°C lower.
Q10 = Vt/Vt-10o
C
for known biochemical reaction 2 < Q10 < 3,
for period of circadian rhythms Q10~1
0
6
![Page 16: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/16.jpg)
From 25 16
Light production in fireflies is due to a type of chemical reaction called bioluminescence. This process occurs in specialised light-emitting organs, usually on a firefly's lower abdomen. The enzyme luciferase acts on the luciferin, in the presence of magnesium ions, ATP, and oxygen to produce light. Genes coding for these substances have been inserted into many different organisms
Firefly
![Page 17: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/17.jpg)
From 25 17
Circadian rhythms of PER2::LUCbioluminescence recorded from knock-in mouse SCN neurons in dispersed culture
From D.K.Welsh et al., Annu. Rev. Physiol., 2010
![Page 18: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/18.jpg)
From 25 18
Activity of dispersed SCN neurons in MED and MUA of SCN in slice preparation
Firi
ng r
ate
(Hz)
![Page 19: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/19.jpg)
From 25 19
Circadian rhythms of PER2::LUC bioluminescence recorded from mouse SCN neurons in slice preparation
![Page 20: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/20.jpg)
From 25 20
1. Nothing is known about messenger(s) between circadian-clockcore and membrane target(s) responsible for circadian peaks of
firing rate
2. Nature of membrane target(s) responsible for circadian peaks of firing rate enigmatic and contradictory
![Page 21: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/21.jpg)
From 25 21
Nature, 2002, 16, 286-290
![Page 22: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/22.jpg)
From 25 22
![Page 23: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/23.jpg)
From 25 23
Nature Neuroscience, 2005, 8, 650-656
![Page 24: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/24.jpg)
From 25 24
Nature Neuroscience, 2006, 9, 1041-1049
![Page 25: Circadian clock in mammals](https://reader035.vdocuments.us/reader035/viewer/2022062405/5560e552d8b42a3d768b4e03/html5/thumbnails/25.jpg)
From 25 25
There are two common features for presented above hypotheses:
1. All experiments were done employing whole cell recordings
2. Spike-associated currents are key targets for circadian modulation of firing rate
Our approach was based on on-cell (i.e. cell-attached) recordings of electrical events in SCN neurons