W14 - Depression 2/2

Question 1

What are depression-like behaviours that can be modelled in mice?

Answer 1

Motivation, anhedonia, negative affect, circadian and endocrine alterations

Question 2

What behavioural paradigm is widely used to model depression?

Answer 2

Chronic social defeat

Question 3

What behavioural changes can be induced to susceptible mice by chronic social defeat?

Answer 3

Social avoidance and anhedonia (lower score in sucrose preference test)

Question 4

True or false: fMRI studies in depressed subjects have only found changes in activity in networks of brain regions of interest?

Answer 4

False: changes in functional connectivity.

Question 5

What might fMRI not be able to capture in terms of depression signature?

Answer 5

Network level dynamics involving interactions of neural activity between spatially separated brain regions on faster timescales that are not captured by fMRI

Question 6

What are local field potentials (LFP) corresponding to electrophysiologically?

Answer 6

Pooled activity of many different neurons up to 1mm away from electrode tip = measure of electrical activity of a population of neurons.

Question 7

What might be inferred from the oscillations of LFP?

Answer 7

Oscillations patterns (amplitude and frequency) could correspond to different cognitive states

Question 8

Is susceptibility usually assessed before or after stress protocol?

Answer 8

After.

Question 9

In Hultman et al., what is “discriminative cross-spectral factor analysis”?

Answer 9

A machine learning model integrating LFP (recorded from 7 mice brain regions) with depression-related behaviours

Question 10

What are electome factors?

Answer 10

Electrical functional connectome factors/networks based on LFP.

Question 11

What behavioural states is the dCSFA model able to differentiate?

Answer 11

1) all mice that went through CSDS from non-stress exposed mice
2) Susceptible vs resilient mice
3) Activity during different segments of the FIT recordings

Question 12

Could electome factors be identified to differentiate:

1) all mice that went through CSDS from non-stress exposed mice
2) Susceptible vs resilient mice
3) Activity during different segments of the FIT recordings

If yes, which and what?

Answer 12

Electome factor 2:

higher activity in stressed mice
higher activity in stress susceptible mice than in resilient mice

Electome factor 3:

higher activity in stress susceptible mice than in resilient mice

Question 13

How can electome factors be identified to be associated with vulnerability to MDD?

Answer 13

Compare electome scores for each electome factors pre-chronic and post-chronic stress.

Question 14

Were Hultman et al. able to identify putative biomarkers of depression with LFP?

Answer 14

Yes, electome factors 1 and 2.

Question 15

Are the different brain regions integrated in single electomes necessarily anatomically connected?

Answer 15

These are statistical relationships and are not constrained by known physical connectivity

Question 16

how can it be verified that EF1 and EF2 could reflect a stress vulnerability pathway?

Answer 16

Testing scores of EF across different models/manipulations known to increase susceptibility to stress (theoretically, activity in EF should follow along)

Question 17

What are known models that induce susceptibility to stress?

Answer 17

• Manipulating a depression-related gene Sdk1
• Chronic interferon alpha treatment
• Early life stress

Question 18

How can it be tested whether the convergent vulnerability network (e.g., EF1) is distinct from depression-like behavior networks?

Answer 18

IF Electome Factor 1 is distinct from the mechanisms of the full depression-like state, then manipulations that reverse depression-like behavioural abnormalities should not affect activity in this Electome Factor (bc. would be only mediating susceptibility)