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Neuroscience IV > all 1-2 weeks > Flashcards

all 1-2 weeks Flashcards

1
Q
A
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2
Q

Structural and functional. Structural used for brain anatomy, functional for living, functioning, dynamic brain imaging.

A

Two types of neuroimaging?Used for?

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3
Q

seconds or fraction of a second High temporal resolution Low spatial resolution

A

structural imaging high/low

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4
Q

minutes Low temporal resolution. High spatial resolution.

A

functional imaging high/low

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5
Q

Lesional study

A

Phileas Cage

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6
Q

Lack of contarast inside the scull.

A

Wilhelm Röntgen

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7
Q

radiography of the ventricles of the brain with the cerebral fluid replaced by air or radiopaque material or labelled with a radionuclide.

Used until 1970s

Risky!!

A

Walter Dandy

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8
Q

EEG

Electroencephalogrphy

Hans Berger (DE)

1924

A

EEG

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9
Q

1934 Epileptic spikes

1953 different stages of sleep

Combined with fMRI to be able to identify whole networks and brain regions involved.

A

Milestones of EEG

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10
Q

CT - computer tomography

[tomos: slice, section]

A

CT

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11
Q

CAT - computer axial tomography

X-ray CT

X-rays from many directions to reconstruct the volume of interest in slices

A

CAT, x-ray CT

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12
Q

Positron Emission Tomography PET

GAMMA rays.

Needs a cyclotron close by making the radioactive molecules. (Radioactivity lasts only for ~30 sec.)

A

PET

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13
Q

Magnetic Resonance Imaging MRI

DTI type of MRI, looking at microstructural changes

A

MRI

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14
Q

functional MRI

resting state fMRI / task-based fMRI

A

MRI

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15
Q

Multimodulling imaging

Often includes several MRI and a few fMRI

A

multimoduling imaging

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16
Q

EEG

Activity measured on a millisecond scale on the surface of the scalp.

Non-invasive

multiple electrodes

Portable and cheap (hat&gel&computer)

A

EEG

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17
Q

MEG - Magnetoencephalography

Measures magnetic fields

Head in a MEG helmet

Low spatial resolution-doesn’t reach to deep brain areas

High temporal, millisecond-level

tolerance, sticking ones head to a massive helmet-like machine, don’t move

A

MEG

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18
Q

PET - Positron Emission Tomography

Measures glucose metabolism

Glucose tagged using radiopharmaceuticals (tolerance highest)

fluorine - 18 (F-18)

fluorodeoxyglucose (FDG)

10-20 sec, mid temporal

whole brain mm scan good spatial

A

PET

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19
Q

functional near-infrared spectoscopy

BOLD

Difference between oxy-deoxyhaemoglobin (in colour)

Measures both oxygenation level and blood volume (excess of oxygenated blood after use/brain activity)

Spatial resolution: 2/4 low (surface 5 cm, small amount of sensors)

Temporal resolution: 3/4 high

Tolerance needed: low, suitable for babys

Works well for babies with their thin scull

A

fNIRS

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20
Q

Blood

Level

Oxygenation

A

BLOOD?Used in which techniques?Based on what?

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21
Q

fMRI - functional magnetic resonance image

Difference between oxy-deoxyhaemoglobin (in colour)

Measures both oxygenation level and blood volume (excess of oxygenated blood after use/brain activity)

Gives very detailed image

every few seconds, low temporal

tolerance needed medium, noisy

A

fMRI

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22
Q

Indirect:

fMRI - based on BOLD, magnetic differences between oxy-deoxyhaemoglobin. Oxygenated blood flooding after use.

fNIRS - also based on BOLD colour difference

Direct:

EEG

A

indirect-direct imaging

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23
Q

strong magnetic field:

deoxyhaemoglobin (Hhb) - paramagnetic

close to nothing magnetic field:

oxyhaemoglobin (O2Hb) - diamagnetic

A

magnetic

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24
Q

fMRI

30 000 (strong enough to lift up a car)

A

What technique:1.5 or 3 Tesla [machine]

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25
Q

MR - magnetic resonance

Wearing no metal in clothing or body.

Magnetic used in MRI scan is 30 000 stronger than earth’s magnetic field.

A

To check that someone is MR compatible?Why is this important

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26
Q

Comparing different stimuli -> activation in different brain areas.

Based on BOLD.

A

What is typically tested using fMRI?

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27
Q

Darker.

Brain activity sips first oxygen in from the nearby environment -> lots of deoxyhaemoglobing, more magnetic perturbation -> initial dip (dark picture)

Followed by overflow of diamagnetic oxyhaemoglobin –> less deoxyhaemoglobin than at rest -> less magnetic perturbation than at rest –> bright colour than t rest

A

BOLD

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28
Q

raw data

preprocessing

(‘clean up’: remove head movements, breathing, cardiac pulsation etc. increase the signal to noise to ratio)

single subject analysis

(general linear model GLM, fix head size etc to the template, where is the individual brain activity compared to experiment model)

group-level analysis

(compare groups, patients/healthy controls)

A

processing data

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29
Q
  • A gene and its encoded protein (and different isoforms)
  • how specific genes and proteins interact
  • the signalling pathway and how it works
  • the formation/ specification of cell types, tissues and organs
  • the circuits and networks in the nervous system
  • the above in relation to disease
A

What is studied with animal models? (

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30
Q

CHORDATA: animals in this category have notochords (not always a vertebrate). Frogs etc. also humans

ARTHROPODA: insects

HUMAN:

Kingdom: Animalia

Phylum: Chordata

Class: Mammalia

Order: Primates

Suborder: Haplorhini

Infraorder: Simiiformes

Family: Hominidae

Subfamily: Homininae

Tribe: Hominini

Genus: Homo
Linnaeus, 1758

A

Chordata?Arthropoda?

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31
Q

500 million years

A

500 milj

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32
Q

Main reason:

understand causes, mechanisms, pathways from molecule to mind

A

Why study animals?

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33
Q

Homology

A

Homology

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34
Q

Homologous genes/proteins

Sequence identity between orthologous genes/proteins from different species

A

Genes homology

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35
Q
  • mutating, inactivating or overexpressing a gene/protein
  • finding interacting/ binding partners
  • screening for enhancers/ suppressors
    of ‘disease gene/protein’
  • epistasis tests and manipulation of a signalling pathway
  • targeted activation/ inactivation of neural circuits
  • the regulation and function of behaviour
A

Methods

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36
Q

Genetic similarities between fly and mouse (and human)

Hirth & Reichert 1999

A

genetic similarities

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37
Q

Baker’s yeast has been used to discover genes and their function in the regulation of the cell cycle/cell division.

A

bakers/brewers yeast

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38
Q

eukaryotic cell

A

eukaryotic cell

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39
Q

cell division of bakers yeast

A

cell division yeast

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40
Q

TDP-43 and FUS genes has been discovered to be involved in the formation of motor neuron disease.

TDP-43 and FUS inhibit the growth of yeast cultures, they build aggregates = they are toxic.

Glucose = gene has been turned off

Galactose = gene has been turned on

A

TDP-43 and FUS

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41
Q

Form aggregates, means they are toxic.

Couthouis et al. (2011)

In human postmortem samples it is visible that human homolog of TAF 15 also forms aggregates in ALS cases, which stands for amyotrophic lateral sclerosis.

Couthouis et al. (2011)

A

TAF-15 and ALS

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42
Q

C. elegans

A

C. elegans

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43
Q

John Sulton 2002

A

Nobel Prize, C. Elegance

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44
Q

L1 - L4

a stage where larva can survive for 4 months, doesn’t mature into an adult.

A

larva, Dauer

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45
Q

daf-2 and daf-16 define lifespan in C. elegans

Kenyon et al. (1993)

High levels of daf-2 causes the suppression of daf-16, which therefore are low, which leads to a normal lifespan, around 25 days.

daf-2 is low, it leads to the derepression of daf-16, which then leads to high levels of this protein, and that extends the lifespan. See image!!

A

daf-2 and daf-16 define …. in C. elegans

46
Q

daf-2 /IGF1 is insulin receptor in humans!

(Affects life span)

Gems & Partridge (2013)

A

daf-2 / IGF1, insulin receptor

47
Q

Drosophila melanogaster

A

Drosophila melanogaster

48
Q

Fruit fly, drosophila melanogaster

A

fully mapped genome

49
Q

1912

Thomas Hunt Morgan

Columbia University

A

Hunt Morgan

50
Q

10-12 days

egg - larva - adult

A

Drosophila melanogaster life cycle?

51
Q

Enhancer in generating transgenic flies.

For example, as an enhancer that is specific for all the dopaminergic neurons.

When all the dopaminergic neurons are active, enhancer is transcriptionally active. It recognises the abstract activating sequence of a second set. That could for example be a green fluorescent protein.

Muqit & Feany (2002)

A

GAL4/UAS system

52
Q

Dopaminergic pathway

Voluntary movement.

Hirth (2010); Strausfeld & Hirth (2013)

A

dopaminergic pathway

53
Q

Forward genetics:

Starting with a mutant phenotype, then identify the protein and the gene (Thomas Hunt Morgan)

Reverse genetics:

Knowing the (human) gene, then going to Drosophila, looked whether it has a human homolog, or a fly homolog in this case, and then we started to manipulate that gene, and then, we could look, how does that relate to the disease.

(picture on the slide wrong?)

A

genetic string

54
Q

Parkinson’s disease, introduced mitochondrial dysfunction in cholinergic, dopaminergic; and serotonergic neurons.

55
Q

Only affected dopaminergic.

A

Parkinsons, dopamin

56
Q

All cells derive from one.

J. Sutton was able to trace this tree in C. Elegance, got a Nobel Price for it.

A

cell lineage

57
Q

It’s vertebrate!

Behaviour

A

The zebrafish: Danio rerio, vertebrate

58
Q

Orger & de Polavieja (2017)

A

Advantages:

59
Q

Transparent embryo

A

transparent embryo

60
Q

72h

3 months

A

72h, 3 months

61
Q

yes

A

live brain imaging

62
Q

Autism

Hyperactivity (night time activity)

Hoffman et al. 2016

A

cntnap2a - autism

63
Q

Estrogenic phenotypic suppressors were able to suppress hyperactivity.

A

Biran & Levkowitz (2016)

64
Q

Mouse

Is a mammal with social behaviour.

90%

A

Mus musculus

65
Q

loss of nigrostriatal pathway

degenerative loss of dopaminergic neurons in the SNpc

(substantia nigra pars compacta)

A

Parkinson’s

66
Q

D1 and D2 affected, Gpi/SNr not inhibited, messages don’t get to thalamus

A

What condition typically follows:

67
Q

Modified with channelrhopsin ChR2-YFP

Channelropsin is a protein that can be activated by light pulse –> over activation of a neuron.

A

Kreitzer’s lab San Francisco

68
Q

Switching neurons on/off by light (for example D1 or D2 neurons in striatum)

A

optogenic activation

69
Q

Enzyme leading to dopamine production

A

tyrosine hydrolaxe

70
Q

It is antagonist of dopamine.

Used to create Parkinson’s model in mice.

71
Q

6-OHDA (dopamin antagonist) blocked the effect of dopamin –> PD model

ChR2 possible to activate with laser (light pulse). When D1 activated mice ran.

When D2 activated mice stopped.

Shows that D1 activation can overcome Parkinsonian phenotype.

Friend&Kravits 2014

A

D1, D2 Parkinson’s, Kreitzer

72
Q

Voltage difference across the membrane of a neuron when it is at rest (non-signalling)

Intracellular -70 mVs, (compared to extracellular 0mV)

A

Resting membrane potential

73
Q

Positive or negative ions is higher/lower in one area than another.

A

Concentration gradient:

74
Q

A change in a neurons membrane potential that makes it more positive (less negative).

A

Depolarisation:

75
Q

A change in a neurons membrane potential that makes it more negative. It is the opposite of depolarization.

A

Hyperplarisation:

76
Q

Transmembrane proteins that form a channel allowing ions to travel in/out of a cell.

These channels are opened when the receptor binds a ligand, like a neurotransmitter.

Glutamate receptors and GABA A receptors are examples of ionotropic receptors.

A

Ionotropic receptors:

77
Q

Transmembrane proteins that form ion channels whose opening and closing is regulated by the membrane potential near the channel.

A

Voltage-gated ion channels:

78
Q

Large voltages generated by animals

(electric eels or rays: electroplaque)

Negative resting membrane potential

(most neurons)

Postsynaptic potentials

(small variable changes in membrane potential)

Action potentials

(large, fast, all or none fashion)

A

types of electric activity

79
Q

An electroplaque has Na/K pump maintaining membrane potential, operates on ATP.

When acetylcholine binds (ionotropic ligand gated) to nicotinic Ach receptor nAchR, sodium (Na+) flows in. depolarisation 120 mV.
Has electroplaques piled up, can create a shock up to 700V (volts)

A

Electroplaque

80
Q

EPSPs are generated by activation of ion channels that let positive ions into the cell –> depolarise neurons.

IPSPs are generated by activation of ion channels that let negative ions into the cell –> hyperpolarise neurons.

81
Q

concentration and length of time the neurotransmitter is in the synaptic cleft

amplitude

A

EPSPs and IPSPs are:• graded in amplitude due to the ….. o

82
Q

Nav and Kv

a) closed, closed
b) open, closed
c) closed inactive, starts open
d) closed inactive, open
e) closed, closed

A

action potential

83
Q

Electric potential in the extracellular space around neurons.

A

field potential

84
Q

Nerve: a bundle of axons.

85
Q

Compound axon potential: the sum of the activity in a number of nerve fibers [axons].

A

Compound axon potential:

86
Q
  • field potentials
  • whole nerve activity
  • multi-unit activity
  • single unit activity
  • multi-electrode arrays (MEAs)
A

Extracellular recording (ER)

87
Q
  • activity within single cells
  • sharp electrodes
  • patch suction electrodes
A

Intracellular recording (IR):

88
Q
  • recording activity of single ion channels
  • patch clamp-type electrode
A

Single channel recording (SCR):

89
Q
  • the electrode is outside but close to the neurons
  • the electrodes pick up only field potentials and low frequency filtered action potentials
  • it is not possible to record Vm rest or post-synaptic potentials
A

Extracellular recording (ER)

90
Q

Stimulating electrode in tissue, Schaffer collaterals.

When stimulus given, activates Sch collaterals –> release of NT onto purkinje neurons in the area of CA1.

One electrode records the fEPSP and another sum of many AP of CA1 neurons = somatic population spike.

O’keefe & Nadel (1978); The Scripps Research Institute (2008)

A

Field potential

91
Q

Whole nerve recording

Frog sciatic nerve

Maximum capacity can be recording, adding voltage over hat won’t change the curve of an AP.

Mark CNS end, place on a dish over stimulating an recording electrodes. Apply olive oil at the ends, ringer in the middle (ions). Silicon grease between containers [conductance all the way through]

Lilley & Robbins (1998)

A

Give an example of whole nerve activity

92
Q

Rattus rattus has been used to separate different axons in the vagus nerve by measuring the intensity of the stimulus and their conducting velocity.

A

separating axons

93
Q

yes

Electrode in rat brain, lateral geniculate nucleus.

Flash of light

Measures the neuron closest by but a neuron further away. Simultaneously measuring two neurons.

A

Multi-unit extracellular recording

94
Q

A human (with DBS electrode) gave consent to a single-unit recording.

Was shown pictures of Halle Berny, neuron showed activity. A picture of Michelle Pfeiffer didn’t cause a reaction.

Association neurons

Quiroga et al. 2009

A

Human single unit recording-

95
Q

64

yes, it doesn’t bug them. Cells can happily grow on it. non invasive

Extracellular activity [outside the axons]

A

Multi-electrode arrays MEA

96
Q

current clamps

voltage clamps

sharp electrodes

patch clamps electrodes

A

Intracellular recording

97
Q

potential difference between two points

98
Q
  1. sharp electrode current clamp
  2. Sharp electrode voltage clamp

Perezoso, 2007

A

Ciona intestinalis

99
Q

- cell-attached patch recording:

pipette forms gigasel on the cell membrane, measures single-cell activity.

- whole cell patch:

inside the cell records all ion channels

- inside out patch, outside out patch:

possible to record single ion channel activity

- perforated patch:

using antibiotics to pore wholes

A

Patch clamp electrode

100
Q

Whole cell patch clamp in current mode.

calcium

A

intracellular calcium

101
Q

Yes, by using patch clamp electrode

[remember pipette, air pressure etc.]

A

Can a single ion channel be recorded?

102
Q

yes (as a part of treatment like DBS) / yes (implanted,anaesthetic) / yes

no / yes (anaesthetic=kept still) / yes

no / yes (anaesthetic=kept still) / yes

A

used in human/animal/in vitro?

103
Q

A

Records activity of the cell in ‘physiological conditions’ Detailed and high resolution recordings of voltages

D

Can’t control voltage

A

advantages / disadvantages current clamp?

104
Q

A

Can control the voltage
Detailed and high resolution recordings of currents

D

unstable

A

advantages / disadvantages voltage clamp?

105
Q

A

reusable, simple electrode solution

D

High resistance

Can be difficult to make

Some damage to the cell

A

advantages / disadvantages sharp electrode?

106
Q

A

Low resistance

Relatively easy to make

Less damage to cell

Dialysis of cell contents

D

Not reusable
Dialysis of cell contents

Complex electrode solution

A

advantages / disadvantages patch electrode?

107
Q

A

Allows the recording in real time of the functional activity of a single protein
Elucidates drug action at molecular level

D

Complex and lengthy analysis

A

advantages / disadvantages single channel?

108
Q

Electrophysiology can record the electrical activity of whole brain tissue, a single neuron or a single ion channel.

A

Electrophysiology can record the electrical activity of wholElectrophysiology can

109
Q

temporal

A

Electrophysiology is..

110
Q

vivo

A

Many electrophysiological approaches can be used in xxxx.

111
Q

Electrophysiology can be used simultaneously or in conjunction with optical, molecular, biochemical and pharmacological techniques.

A

Electrophysiology can be used simultaneously

Neuroscience IV (9 decks)

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