model organisms in neuroscience

Question 1

why do we need models in research

Answer 1

• ethical & practical limitation in human studies
• reduces complexity
• avoid confounding variables

Question 2

what are the three type of models and what do their names mean

Answer 2

ex vivo - patient samples
in vivo - animal models
in vitro - cellular models

Question 3

advantages of post mortem tissue (ex vivo)

Answer 3

closest you can get to the actual disease

Question 4

disadvantages of post mortem tissue (ex vivo)

Answer 4

• post mortem changes
• expression affected by freezing conditions
• cannot detect early changes due to disease
• cell type composition may affect results
• genetic variation confounds results
• difficult to perform functional studies

Question 5

advantages of animal models (in vivo)

Answer 5

• animals share many genes w/ human genome
• allows functional test of hypothesis
• allow behavioural studies in response to pertubation e.g. altering diet or changing gene expression

Question 6

disadvantages of animal models (in vivo)

Answer 6

• some aspects of development, genetics, pathology & disease mechanisms are specific to humans

Question 7

what is the connectome map

Answer 7

• know where each neuron arises & what it connects to
• can understand principles of neuronal circuits and make predictions & manipulate circuits to test them

Question 8

how many neurons in c.elegans

Answer 8

302

Question 9

what are advantages of fruit fly (drosophila melanogaster) as model

Answer 9

• 100,000 neurons
• low to maintenance cost
• characteristic anatomy -> can be used as phenotypes
• highly conserved genetic makeup
• powerful model to understand neural circuits and neurodegeneration

Question 10

advantages of zebrafish (danio rerio) as model organism

Answer 10

• 78,000 neurons in larval zebrafish
• external development
• embryos and larva are transparent
• genome is fully sequenced (60% homology w/ humans)
• low maintenance cost

Question 11

why are rodents good model organisms

Answer 11

• 70 million neurons in mouse
• 85% homology between human & mouse genomes
• ability to perform genetic manipulation
• structural simalarity between mice & human brains

Question 12

what big experiment was mouse used as model

Answer 12

genome editing with CRISPR cas9

Question 13

what experimental studies occured w/ danio rerio

Answer 13

system of blood vessels and development of motor neurons

Question 14

what are advantages of non human primates as model organisms

Answer 14

• 99% homology between human & non human primate genome
• they participate in complex social structures -> important in studying human behavioural or social disorders

Question 15

disadvantages of non human primates as model organisms

Answer 15

• genetic manipulation is difficult
• ethical considerations

Question 16

advantages of in vitro models

Answer 16

• model investigates human cells
• mutant protein expressed at physiological levels
• can be used to model sporadic diseases
• compatible w/ large scale screening

Question 17

disadvantages of in vitro models

Answer 17

• cells are not present in their in vivo architecture
• IPSC derived neurons are largely foetal
• they do not always predict in vivo behaviour
• they cannot capture the inherent complexity of organ systems & human body

Question 18

how do fibroblasts turn into induced pluripotent stem cells (IPSC)?

Answer 18

introducing key transcription factors (OCT4, SOX2, KLF4, MYC)

Question 19

what type of neurons are used in modelling ALS with patient derived iPSC

Answer 19

iPSC derived motor neurons

Question 20

what are brain organoids

Answer 20

when cells aggregate in suspension, self organise & differentiate forming structures that are very similar to those found in early brain development

Question 21

why are organoids not mini brains

Answer 21

• they don’t have precise structure
• they don’t have all the functional regions found in humans brains

Question 22

what are advantages of computational models (in silico) as model organisms

Answer 22

• study diseases in silico
• test lots of parameters in parallel
• rapidly generate hypothesis that can be tested in experiments
• reduce the need for experimentation
• potential to accelerate research & reduce costs

Question 23

what are disadvantages of computational models (in silico) as model organisms

Answer 23

don’t have a complete model of the brain