Things I Forget Flashcards
(31 cards)
PK2
Prokineticin 2
Major output of the SCN.
Rhythmic expression (peaks at L/D transition)
Used as a reporter for SCN output (mostly –> hypothalamus).
Output from shell suppresses locomotor activity.
Photic and Non-Photic Input to SCN
Photic = excitatory (from retina via RHT - uses glutamate and PACAP)
Non-photic = inhibitory (from IGL via GHT - uses GABA and neuropeptide Y; from median raphe - uses serotonin). Dorsal raphe neurons also innervate IGL (serotonin).
When do Per/Cry levels peak in SCN?
Build up during day and peak at transition from day –> night
What compensates for Clock KO?
Npas2 (means Clock KO is still rhythmic)
What does Casein Kinase 1 (CK1) do?
Sets speed of the clock by binding PER (promotes degradation)
Major Neuropeptides of the SCN? Receptors and what they do.
AVP (Rs = V1a & V1b) & VIP (R = VPAC2)
Used for intercellular signalling within the SCN –> coordinated, high amplitude output.
AVP important for resistance to SCN network perturbation.
AVP receptor KOs are resistant to jetlag because amplitude is lower (so easier to reset).
VIP involved in photic entrainment of SCN.
Insect equivalent of VIP
Pigment Dispersing Factor (PDF)
Extra-SCN brain clocks
Case studies: limbic system (BNSTov & CeA), epithalamus (habenula), mediobasal hypothalamus
[Oscillations found in olfactory bulb, ventrolateral preoptic nucleus, arcuate nucleus, pituitary and pineal gland.
None in piriform cortex, substantia nigra
Found using slices (isolated from SCN) and per1::luc]
BNSTov and CeA
oval nucleus of the bed nucleus of stria terminalis, central amygdala - both involved in limbic system
SIRT1
An HDAC (NAD+-dependent histone deacetylase). Regulator of epigenetic control. Binds Bmal1 promoter, activates transcription
Cell type in cartilage
Chondrocytes
3 Neural Systems Controlling Sleep
Forebrain system (independently supports SWS) Brainstem system (activates forebrain --> wake) Pons system (triggers REM)
Wake Promoting Areas of the Brain
TMN (tuberomammillary nucleus) in hypothalamus, uses GABA & histamine
Dorsal raphe in the brainstem (serotonin)
LC in the brainstem (NA)
LDT/PPT in the brainstem (ACh)
Make up ARAS system
Cells that generate REM
ACh cells in the brainstem (can be active during wake and REM, unlike other cells. Not active in SWS).
How are EEG sleep states generated?
Activity in the brainstem (DR, LC, LDT/PPT) –> inputs to thalamocortical cells –> DECREASES thalamic rhythmic bursting & related synchrony of cortical targets.
Asynchronous activity is associated with WAKE.
How does light regulate sleep?
Light drives sleep cycles EVEN WITHOUT SCN.
Occurs via melanopsin photoreception.
mRGCs project to the VLPO as well as the SCN (the VLPO regulates SWS).
Inhibitory (GABAergic) neurons of the VLPO are activated –> switches off the ARAS
2 Types of Immune Response & cell types
Inate (1st line of defence, non-specific) or Adaptive (acquired immunity, pathogen specific)
Inate involves macrophages and mast cells. Adaptive involves B cells and T cells.
Shift work associated with…
Increased risk of cancer, metabolic disease, obesity, cardiovascular disease, chronic inflammatory disease
CAPRA-1
circadian administration of Prednisone in rheumatoid arthiritis
Where is the FEO?
Hypothalamus and brainstem have many areas that sense energy-related cues from the periphery (liver, muscle etc).
Hypothalamic nuclei = strong candidates
E.g. Arcuate nucleus (dictates food and energy expenditure, contains orexigenic and anorexigenic cells, coupled to areas involved in neuroendocrine function (PVN, DMN).
Clock genes essential for food entrainment?
Can KO most clock genes and FAA is normal (even though they might be arrhythmic) - including Bmal1, Per1, Clock…
Mutations in Per2 (still have the protein but can’t interact) do not have FAA.
Reverbalpha KO have no FAA or counter regulatory decrease
Why have such robust food entrainment system?
1) energy = essential to survive
2) food may appear at variable times relative to other cues (such as light)
How does the clock respond to energy status/metabolism?
Reverbalpha binds to RORE and RevDR2 sites.
It brings with it repressive complexes such as HDAC3 and NcoR1.
Binding of Reverbalpha to DNA occurs rhythmically.
Taking out Reverbalpha –> lose rhythmicity AND ability to repress gene.
PPAR
Peroxisome Proliferator-Activated Receptors (nuclear hormone receptors). Many actions across body, generally positive metabolic outcome.
Ligands are primarily fatty acids (nutrient cue).Rhythmic, driven by the clock but also directly regulate clock gene expression by binding PPREs (response elements).
