Ras Activity Oscillates in the Mouse Suprachiasmatic Nucleus and Modulates Circadian Clock Dynamics

2015 ◽  
Vol 53 (3) ◽  
pp. 1843-1855 ◽  
Author(s):  
Tsvetan Serchov ◽  
Antje Jilg ◽  
Christian T. Wolf ◽  
Ina Radtke ◽  
Jörg H. Stehle ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus

scholarly journals GABA transporters regulate tonic and synaptic GABAA receptor-mediated currents in the suprachiasmatic nucleus neurons

2017 ◽  
Vol 118 (6) ◽  
pp. 3092-3106 ◽  
Author(s):  
Michael Moldavan ◽  
Olga Cravetchi ◽  
Charles N. Allen
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Dependent Manner ◽  
Circadian Period ◽  
Gaba Concentration ◽  
Gaba Transporter ◽  
Concentration Dependent Manner ◽  
Gaba Transport ◽  
Gaba Transporters ◽  
Tonic Current

GABA is a principal neurotransmitter in the hypothalamic suprachiasmatic nucleus (SCN) that contributes to intercellular communication between individual circadian oscillators within the SCN network and the stability and precision of the circadian rhythms. GABA transporters (GAT) regulate the extracellular GABA concentration and modulate GABAA receptor (GABAAR)-mediated currents. GABA transport inhibitors were applied to study how GABAAR-mediated currents depend on the expression and function of GAT. Nipecotic acid inhibits GABA transport and induced an inward tonic current in concentration-dependent manner during whole cell patch-clamp recordings from SCN neurons. Application of either the selective GABA transporter 1 (GAT1) inhibitors NNC-711 or SKF-89976A, or the GABA transporter 3 (GAT3) inhibitor SNAP-5114, produced only small changes of the baseline current. Coapplication of GAT1 and GAT3 inhibitors induced a significant GABAAR-mediated tonic current that was blocked by gabazine. GAT inhibitors decreased the amplitude and decay time constant and increased the rise time of spontaneous GABAAR-mediated postsynaptic currents. However, inhibition of GAT did not alter the expression of either GAT1 or GAT3 in the hypothalamus. Thus GAT1 and GAT3 functionally complement each other to regulate the extracellular GABA concentration and GABAAR-mediated synaptic and tonic currents in the SCN. Coapplication of SKF-89976A and SNAP-5114 (50 µM each) significantly reduced the circadian period of Per1 expression in the SCN by 1.4 h. Our studies demonstrate that GAT are important regulators of GABAAR-mediated currents and the circadian clock in the SCN. NEW & NOTEWORTHY In the suprachiasmatic nucleus (SCN), the GABA transporters GAT1 and GAT3 are expressed in astrocytes. Inhibition of these GABA transporters increased a tonic GABA current and reduced the circadian period of Per1 expression in SCN neurons. GAT1 and GAT3 showed functional cooperativity: inhibition of one GAT increased the activity but not the expression of the other. Our data demonstrate that GABA transporters are important regulators of GABAA receptor-mediated currents and the circadian clock.

4. Shedding light on the clock

2017 ◽  
pp. 45-61
Author(s):  
Russell G. Foster ◽  
Leon Kreitzman
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Physical Exercise ◽  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Human Body ◽  
Circadian Clocks ◽  
Autonomic Nervous ◽  
Over Time ◽  
Daily Patterns

Most circadian clocks make use of a sun-based mechanism as the primary entraining signal to lock the internal day to the astronomical day. For nearly four billion years, dawn and dusk has been the main zeitgeber that allows entrainment. Circadian clocks are not exactly 24 hours. So to prevent daily patterns of activity and rest from freerunning over time, light can reset the clock. ‘Shedding light on the clock’ explains that the main circadian clock has been located in the suprachiasmatic nucleus in the hypothalamus. This also regulates the activity of the autonomic nervous system, but there are clocks in virtually every cell in the human body. Other zeitgebers include food, physical exercise, and temperature.

scholarly journals Regulation of vasoactive intestinal polypeptide release in the suprachiasmatic nucleus circadian clock

Neuroreport ◽  
2010 ◽  
Vol 21 (16) ◽  
pp. 1055-1059 ◽  
Author(s):  
Jessica M. Francl ◽  
Gagandeep Kaur ◽  
John David Glass
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Vasoactive Intestinal Polypeptide ◽  
Intestinal Polypeptide
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