week 6 - adult hippocampal neurogenesis

Question 1

what is adult neurogeneisis

Answer 1

the process in which neurons are generated from neural stem ells in the adult

Question 2

where do we have neural stem cells?

Answer 2

throughout the brain and the spinal chord

Question 3

What can neural stem cells produce

Answer 3

neuron
oligodendrocyte
astrocyte

Question 4

eevidence for adult neurogeneis:
altman and das (1965)

Answer 4

used autoradiography and histological evidence to suggest adult neurogenesis exists

Question 5

where does adult neurogenesis occur (rodents)?

Answer 5

in the hippocampus. In the subventricular zone of the lateral ventricals and in the subgranular zone of the dentate gyrus

Question 6

what is the pathway of adult hippocampal neurogeneiss in the dentate gyrus (rodents)

Answer 6

the cells proliferate in the dentate gyrus. Then they migrate and differentiate, formign synapses with fibres from the entorinhal cortex.

Question 7

What experiments shows hippocampal neurogenesis in adult humans

Answer 7

spalding et al 2013
- used C14 from nuclear bomb to see if they if there was c14 in neurons which will show if the neurons are new. They only showed c14 in neurons in the dentae gyrus of the hippocampus which is where the rodent models showed adult neurogenesis too

zhou et al 2022

read these papers and summarise what they say

Question 8

where is there evidence of adult neurogenesis in humans?

Answer 8

in the dentate gyrus in the hippocampus

(not in the SVZ in humans)

Question 9

what do quantitative studies say about neurogenesis

Answer 9

We create 700 new neurons per day in the hippocampus in the adult. By the time we turn 50 we will have replaced the entire granule cells

Question 10

What experiments show that the neurogenic niche is important in neurogenesis

Answer 10

Take a neural stem cell from a spinal cord. Grow the neural stemcell in a dish. If you transplate it into the dentate gyrus you get neurons
If you transplant it into a non-neurogenic region you dont get neurons.
This shows that the neurogenic niche is very important here

Question 11

What experiments can tell us about the neurogenic microenvironment

Answer 11

song et al 2002 compaired the amount of astrocytes with whether stem cells become neurons and found that it is the astrocyttes in the hippocampus that are sending this signal. The younger the astrocytes the better.
Read this paper.

Question 12

What are the molecular control of adult neurogenesis?

Answer 12

Lie et al, 2004
- back in 2004 they only knew that there was some repression in the niche of not making astrocytes so much

Mu, lee and gage 2010
- Found hundreds of factors that are key players in modulating neurogenesis

Choose one factor thats listed in the 2010 paper that i recognise from another coourse and read a couple of papers about how they modulate neurogenesis

Question 13

what is one example of a factor that contributes to molecular control of neurogenesis

Answer 13

wnt signalling regulates adult hippocampal neurogenesis (lie et al 2005)

Wnt is found in the granule cells, where neurogenesis happens.

Found that when you add Wnt, you get more new neurons from the stem cells compared to when you don’t add wnt

when wnt signalling was blocked.. check this

astrocytes express wnt

Question 14

What is the functional relevance of adult hippocampal neurogenesis?

Answer 14

• adult hippocampus is reduced in some animal models of depression. Many treatments for depression promote neurogenesis and strudies show that treatment efficacy is dependent on this.

Samuels and hen 2011,
bbc radio 4 discussion
Anacker and hen 2007

new granule neurons:
- increase spatial memory capacity - the more neurogenesis the better performance in mwm . If you block neurogenesis then that eliminates performance in mwm. (thuret et al 2009)
- improve pattern seperation (read paper from clelland et al 2009. Having new neurons can permit the second event to utilize new neurons instead of the same old neurons to encode the event in different contexts)
-Involved in forgetting/clearence of established context memories (infantal amnesia. we don’t remember when we were an infant because at early childhood we have burst of neurogenese which distrubs this. read Frankland et al, 2014. Increasing neurogenesis weakened existing memories in mice but allows the encoding of new conflictin information. Decreasign neurogenesis stablizied existing memories but impeded the encoding of new conflicting information)
- Add information about time to new memories. (aimone et al, 2013 - computational modelling to suggest that the temporal proximity of two events is sufficient to lead to a relationship in their long term episodic memories. in contrast, another event later would not be associated due to time elapsed. Thsi may be because the overlapping young neurons would have a temporal association. But when time has passed, different young neurons creates temporal seperation)

Question 15

what is the relevance of adult hippocampal neurogenesis in neurodegenerative disease

Answer 15

look at these reviews

mu and gage 2011
maruszak 2013
berger et al 2020

conflicting information - some show increase in neurogensis in AD, some show decrease

Question 16

how can we modulate adult hippocampal neurogenesis?

Answer 16

• learning increases neurogenesis
• chronic stress decreases neurogensis
• chronic sleep deprivation decreases neurogenesis
• sex increases neurogenesis
• ageing decrease neurogenesis (villeda et al 2011, fused circulatory system of mice, young old , old old, and young youong. - crazy study , read it)
• excercise increases neurogenesis (praag et al 1990. Thuret et al 2009 - in mice that don’t have neruogenesis, running can rescue it and lead them to get neurogenesis)
• diet (diet has strong impact on neurogeneis - read a review (marx et al 2021)

Question 17

what is the main paper to read that overviews all of this?

Answer 17

adult neurogenesis in the hippocampus: from stem cells to behvaiour
goncalves et al 2016)