Lecture 3 Clock circuits in the mammalian brain Flashcards

1
Q

PVN

A

paraventricular nucleus

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2
Q

AHA

A

Anterior hypothalamic area

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3
Q

sPVNz

A

subparaventricular zone

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4
Q

SCN

A

suprachiasmatic nucleus.

light entrainable circadian pacemaker.

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5
Q

OX

A

optic chiasm

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6
Q

anatomy of hypothalamus?

A

2x SCN, seperated by the third ventricle.

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7
Q

SCN neurons properties?

A

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

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8
Q

where does SCN recieve monosynaptic input from?

A

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.

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9
Q

what is the main RHT neurotransmitter?

A

glutamate, augmented by PACAP

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10
Q

what is PACAP?

A

pituitary adenylate cyclase activating polypeptide.

located heavily in the ventral SCN (found via immunostaining).

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11
Q

What comprises the GHT?

A

Neurons in the intergeniculate leaflet (IGL) of the visual thalamus project to the SCN, forming the geniculohypothalamic tract (GHT)

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12
Q

What neurotransmitters does the GHT use?

A

GHT input uses both GABA and Neuropeptide Y (NPY); these are inhibitory; this input hyperpolarises and suppresses SCN neurons.

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13
Q

How does the MR innervate the SCN?

A

Neurons in the Median Raphe (MR) innervate the SCN; they contain serotonin (5-Hydroxytryptophan or 5-HT); this input suppresses SCN neuronal activity.

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14
Q

How does the DR innervate the IGL?

A

Neurons in the Dorsal Raphe (DR) innervate the IGL; they contain 5-HT

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15
Q

describe non photic inputs to the circadian system

A

IGL - GHT
MR
DR

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16
Q

describe photic inputs to the SCN

A

RHT

17
Q

what happens if a glutamate antagonist is given before a light pulse?

A

reduces phase shift, therefore glutamate is the NT.

18
Q

What happens if arousal promoting occurs during the day/night?

A

day- phase advance

night - no change

19
Q

phase response curves for photic and non photic?

A

photic (light pulse yada yada)

non photic - advances during inactive phase, small effect of delay in active phase.

20
Q

neurochemicals of RHT?

A

glutamate and PACAP

21
Q

neurochemicals of GHT?

A

Neuropeptide Y and GABA

22
Q

neurochemicals of brain stem?

A

5-HT

23
Q

neuropeptides made by SCN neurons?

ventral

ventral/dorsal

dorsal

A

intrinsic, following are ventral:
Vasoactive Intestinal Polypeptide (VIP) ,Gastin-releasing peptide (GRP), Substance P (SP)

Ventral/dorsal:
Vasopressin (AVP)

Dorsal:
Somatostatin (SOM)

24
Q

what is the core and shell model?

A

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.

25
Q

Evidence that the SCN contains the main circadian clock?

A

When SCN lesioned arrythmic in DD, transplant restores.

26
Q

SCN activity throughout day?

A

neuronal and molecular rhythms high in day low at night

BEHAVIOURAL RHYTHMS OPPOSITE

27
Q

In vitro single unit recordings of cultured SCN neurons?

A

rhythmically express electrical activity -24 hr.

higher at one point of the day.

therefore clock acitivty is a product of individual cells.

28
Q

how are clock genes expressed in the SCN in vivo.

A

rhythmically with peak activity in the day (Per1, Per2, Cry1, Bmal1, AVP)

29
Q

Per1::luc study of individual SCN cells

A

SCN stays rhythmic for weeks, individual SCN neurons function as autonomous clocks.

30
Q

SCN neuron metabolism?

A

higher during day than night.

31
Q

when does PER gene expression peak?

A

during day.

32
Q

outputs of SCN?

A

Hypothalamus:
aPVN to influence corticotrophin releasing hormone and melatonin frmo pineal gland.

sPVNz
DMH
MPN

Thamalus:
PVN
paratenial nucleus
LGN

33
Q

PK2?

A

Prokineticin 2.
Suppresses locomotor activity.
High during day

34
Q

relationship between clock gene expression and electrical activity

A

Peak spontaneous firing rate and ZT 7 followed by peak GFP (per1) expression at ZT9