Lecture 2 Clock circuits in the mammalian brain Flashcards
PVN
paraventricular nucleus
AHA
Anterior hypothalamic area
sPVNz
subparaventricular zone
SCN
suprachiasmatic nucleus.
light entrainable circadian pacemaker.
OX
optic chiasm
anatomy of hypothalamus?
2x SCN, seperated by the third ventricle.
SCN neurons properties?
v small 8-12um.
densely packed.
neurochemically heterogeneous - most contain GABA, but also contain a variety of different neuropeptides, spatially segregated to different subregions of the SCN
where does SCN recieve monosynaptic input from?
retina via the retinohypothalamic tract (RHT).
RHT inputs are primarily to ventral parts of the SCN.
RHT synapses are excitatory (gray type I, therefore the depolarise and activate SCN neurons.
what is the main RHT neurotransmitter?
glutamate, augmented by PACAP
what is PACAP?
pituitary adenylate cyclase activating polypeptide.
located heavily in the ventral SCN (found via immunostaining).
How is the GHT formed?
Neurons in the intergeniculate leaflet (IGL) of the visual thalamus project to the SCN, forming the geniculohypothalamic tract (GHT)
What neurotransmitters does the GHT use?
GHT input uses both GABA and Neuropeptide Y (NPY); these are inhibitory; this input hyperpolarises and suppresses SCN neurons.
How does the MR innervate the SCN?
Neurons in the Median Raphe (MR) innervate the SCN; they contain serotonin (5-Hydroxytryptophan or 5-HT); this input suppresses SCN neuronal activity.
How does the DR innervate the IGL?
Neurons in the Dorsal Raphe (DR) innervate the IGL; they contain 5-HT
describe non photic inputs to the circadian system
IGL - GHT
MR
DR
describe photic inputs to the SCN
RHT
what happens if a glutamate antagonist is given before a light pulse?
reduces phase shift, therefore glutamate is the NT.
What happens if arousal promoting stimulit is exposed during the day/night?
phase advance
night - no change
phase response curves for photic and non photic?
photic what described before.
non photic - advances during inactive phase, small effect of delay in active phase.
neurochemicals of RHT?
glutamate and PACAP
neurochemicals of GHT?
Neuropeptide Y & GABA
neurochemicals of brain stem?
5-HT
neuropeptides made by SCN neurons?
intrinsic, following are ventral:
Vasoactive Intestinal Polypeptide (VIP) ,Gastin-releasing peptide (GRP), Substance P (SP)
Ventral/dorsal:
Vasopressin (AVP)
Dorsal:
Somatostatin (SOM)
what is the core and shell model?
Shell - AVP cells located.
Core - VIP/GRP cells located.
Core recieves input from the RHT.
Core weak clock cells.
Core projects to shell, AVP cells are strong clock cells.
Evidence that the SCN contains the main circadian clock?
When SCN lesioned arythmic, transplant restores.
SCN activity throughout day?
high when inactive, low during active, GABA so probably inhibit. Rats.
In vitro single unit recordings of cultured SCN neurons?
rhythmically express electrical activity -24 hr.
higher at one point of the day.
therefore clock acitivty is a product of individual cells.
how are clock genes rhymically expressed in the SCN in vivo.
nice rhythms, mPer2, 1
mBmal1, mCry1, AVP
Per1 luceferin
luceferin comes from firefly - glow.
per1 also makes luceferin.
SCN stays rhythmic for weeks, individual SCN neurons function as autonomous clocks.
SCN neuron metabolism?
higher during day than night.
when does PER gene expression peak?
during day.
outputs of SCN?
Hypothalamus:
aPVN to influence corticotrophin releasing hormone and melatonin frmo pineal gland.
sPVNz
DMH
MPN
Thamalus:
PVT
paratenial nucleus
LGN
how does SCN molecule and cellular rhythm change during the day in relation to behavioural activity?
SCN molecular and cellular rhythms peak in the day,
behavioural Activity low in day, high at night
PK2?
Prokineticin 2.
Suppresses locomotor activity.
High during day (for what?)
