Adult Neurogenesis

Question 1

What is neurogenesis?

Answer 1

Stem cells producing new neurons in development and adulthood.
A proliferative process that lasts 4 weeks, in the 1st week, most cells will die off.
Type 1, 2, 3, newborn neuron, immature neurons and mature granule cell.

Question 2

What can affect maturation of neurons?

Answer 2

Deplete it: cosmic irradiation, drugs of abuse, stress, x radiation, seisures (neonatal).

Increase it: antidepressants, deep brain stimulaion, running (seizures (adult)

Question 3

Where are neurogenic zones in adulthood

Answer 3

In the Hippocammpus, the Subgranular zone (SGZ) of the dentate gyrus.
and
Subventrical zone too (SVZ)

Question 4

What are methods to detect neurogenesis?

Answer 4

Cellular markers that are only present at a certain phase of the life cycle. This is how we quantify the types. (whos maturing/surviving)

i.e. Nestin, GFAP, DCX, Tubulin, Clretinin, NeoN, calbindin.

Question 5

What are the different characteristics for immature and mature neurons?

Answer 5

Immature neurons:
They have a lower threshold for LTP, <4weeks old
Going through synaptic integration, highly excitable and under LOW inhibition

Mature neurons: >4weeks old. Lowered excitability and under high inhibition

Question 6

What are the functions of the hippocampus?

Answer 6

Memory:
- working memory, long term memory, spatial navigation

Emotional Behaviors: Anxiety, depressive behaviors, addiction, impulsivity.

When neurogenesis is altered, you see changes in these behaviors. i.e. increase in neurogen can buffer stress response. and depression shrinks hippo but antidepressants can buffer this effect.

Question 7

What factors effect neurogenesis?

Answer 7

Increase: exercise, injury (regulating growth factors), neurostimulation, learning, enriched environment, antidepressants.

Decrease: stress, aging, disease, disorders (depression), radiation, alcohol, drugs and nicotine.

Question 8

How do we study new cells? (5)

Answer 8

1. Elimnate newborn cells altogether (kill of dividing cells) and look at transgenic models without the neurogen
2. Inhibit/activate cell populations, by using a virus or optogenetics
3. Increase cell proliferation and survival. Use drugs that slow death or manipulate naturally with exercise and enrichment. -assess existing circuitry and learning
4. Use fluorescent virus to visualize them (like quantify of dendritic spines) ****BECCA SEND HELP
5. Use DNA markers at different ages to access proliferation and activity.
   - BrdU is a synthetic DNA analog that is injectable, and encorporates into dividing DNA where thyamine would, and shows cells that timestamp cell birth.

Question 9

What has neurogenesis been linked to performance in?

Answer 9

Spatial memory tasks: Water maze
Object memory
Fear conditioning memory
Pattern separation
Stress response (buffering)

Question 10

What is the functional significance of adult neurogenesis?

Answer 10

1. Turnover hypothesis: replace old and dying ones
2. Provide new connections to faciliate learning and meomry, allow for distinct coding to maintain memory specifics (pattern separation)
3. Cognitive decline and memory performance (lower neurogen in diseases and old age)

Question 11

How does neurogenesis help pattern separation?

Answer 11

Activates totally different populations that are further apart from each other, different populations for different events when new neurons are made to help
**
Sparse coding, not a lot of firing at once to allow for inhibition and distinct memory traces.

Question 12

How does inhibiiton work in the dentate gyrus?

Answer 12

Reducing noise from other cells, feedback causing inhibtion of neurbouring cells, and NEWBORN CLELS INDUCE GREATER INHIBITION

Question 13

How could we inhibit neurons at different ages?

Answer 13

Chemogenetic virus that expresses receptors that hyperpolarize cells, effects channels and allows for inhibition when you apply a drug.
CNO is a ligant that inhibits it.
Activity marker FOS- immediate activity

Using BrdU+ as a cell age marker and Fos+ as an activity marker.

Question 14

What did alyssa find in her research?

Answer 14

Adult born neurons are selecting which neurons are activated during learning and memory by inhibiting neurobouring OLDER neurons. This constrains activity to allow for creation of sparse specific memory trace.

Question 15

Does neurogenesis induce forgetting?

Answer 15

When there is a greater inhibitory tone in DG this could caused reduced encoding/retrieval abilities.
= shown mostly in forgetting recently aquired memories in rats.

maybe why didn’t don’t remmeber things from early childhood

Question 16

Is human neurogenesis a thing?

Answer 16

We can only look at people post mortem, other methods lead to false negatives. Processing tissues limits immunihistochemistry.
difficult to study.
There is a lot of research for it, and at different time points. Doublecortin is a strong indicator of immature neurons.
It also happens at the SAME TIME AS ANIMAL MODELS over the lifespan.
Maybe there aren’t a hwole lot of new cells being added but htey just contribute a lot towards inhibition?
*** last few slides.