The plastic brain

[En español]

We are born with roughly 100 billion neurons, more neurons than we’ll ever have again. It’s still a ton of neurons; they could wrap around the earth 3-4 times. Plus, each of these 100 billion neurons has a couple hundred to thousand connections with other neurons. But as we age, our brains also change. Regions of the brain key for memory and cognition shrink, neurons get worse at communicating with each other, and blood flow decreases (5).  Does this mean it’s all downhill from birth?HippoCount

Neuroscientists thought that neurogenesis, or the birth of new neurons, only happened while the brain was developing and creating those 100 billion neurons we are born with. This assumption made sense for two reasons: First off, stem cells weren’t thought to exist in the adult brain, and neurons are too complex to multiply and create new cells. This was solved when stem cells were found. There is a second, more philosophical concern – if new cells are always being born, how do we retain a sense of self? Let’s come back to this one after we go over the basics of brain development.

The developing brain

Turns out, our 100 billion neurons come from a tube of tissue that forms on an embryo around week four of development. The cells that comprise this tissue (radial glial cells and IPC for intermediate progenitor cell in the picture below) divide and become the cells that make up our brains, like including neurons and glia (another incredibly important type of brain cell). Then, these young neurons migrate to specific brain regions in a variety of ways, including actually sliding along those glia. Neural migration is treacherous; only a third actually make it to the right place, and many neurons die along the way (1)!  Once the select few reach their final destination, they extend axons and dendrites, the connections that allow them to communicate with other neurons.

neuwrite_development

 

Eureka! Adult neurogenesis in the human

Until the 1990s, neuroscientists though the human brain stopped creating cells and the major connections between groups of cells after this initial developmental stage. Then, in 1998 Fred “Rusty” Gage published a paper showing that 72 year old human brains were still making new neurons (6).  Today, his finding that neurogenesis happens in the hippocampus, and specifically dentate gyrus, of the adult human brain has been well-replicated. This is pretty cool, because the dentate gyrus plays a key role in memory consolidation and recall!

Gage2002_GFPneurogen

So about 800 new neurons are being made every day in the dentate gyrus, but according to Rusty Gage, just being born isn’t enough. During our interview, Rusty asserted that new neurons “have to have input early on, or they die”. Until neurons mature their survival is activity dependent. If you block activity, new neurons don’t integrate into the existing network and subsequently die. One way neurons connect with each other is by firing at the same time; you may have heard the concept “fire together wire together”. So these new neurons are constantly firing action potentials early on as they make connections, and slowly become quieter as they are fully integrated into the existing network.

Turns out, these new neurons play a specific role in the dentate gyrus. Neurons in the dentate gyrus are generally quiet and inactive, and only respond to really specific things. But, as we learned, new neurons are firing all the time. So, these new neurons may help us distinguish between really similar events that are only separated in time, something we do all the time. For example, you can distinguish between yesterday when you sat under a tree in your backyard vs. when you sat under it a few months ago – even if it was sunny and you were eating an apple both times. Those neurons born a few months ago probably help us do this!

Neuwrite_ENGRAM

 

Can we influence neurogenesis?

Interestingly, neurogenesis isn’t constant. Exercise increases  proliferation, or the sheer number of new neurons, about 150% over control levels. However, only 56% are still alive after 4 weeks. On the flip side, you can also put animals in an enriched environment, or a cage with lots of other animals and toys. This doesn’t increase proliferation, but instead helps neurons integrate – 85% of the new neurons end up surviving!  Furthermore the figure on the right below shows how exercise can help combat the decreased neurogenesis that accompanies aging (7,8).

 

GageReplot

 

We can use this to our advantage. Our memories are notoriously malleable; whenever we recall a memory we incorporate stuff that’s going on in the present, slowly changing the memory over time. Turns out, this isn’t always a bad thing (like it is for eyewitness testimonies)! People with PTSD don’t have this ability when recalling the traumatic event, when they recall it it’s as crystal clear as the first time. Turns out, PTSD may suppress neurogenesis , as stress is well known to do (3,4,5). Luckily, the findings outlined above suggest a treatment regime for dealing with traumatic memories. Perhaps people with PTSD could consider exercise and an antidepressant regime to get neurogenesis going again. Then, in a safe setting, a clinician could ask them to recall the stressful event. Then, the next time they bring up the memory its layered with the context of the very safe environment, slowly but surely making that memory less traumatic.

Hen_Stress

So, back to that question of how we retain a sense of self if there are all these new neurons being born. Adult neurogenesis hasn’t been found in many areas of the brain. In the dentate gyrus, it probably has a really specific role in helping us tell memories apart. However, this theory rests on adult human neurogenesis happening only in only a few specific regions – if it’s discovered in more parts of the brain, we will have to revisit this question of how we retain a sense of self in a future post.

Citations

  1. http://www.ninds.nih.gov/disorders/brain_basics/ninds_neuron.htm
  2. http://umaine.edu/publications/4356e/
  3. http://newsroom.cumc.columbia.edu/blog/2013/01/18/neurogenesis-and-anxiety-disorders/
  4. Snyder, J. S., Soumier, A., Brewer, M., Pickel, J., & Cameron, H. A. (2011). Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature, 476(7361), 458-461.
  5. https://www.nia.nih.gov/alzheimers/publication/part-1-basics-healthy-brain/changing-brain-healthy-aging
  6. Eriksson, P. S., Perfilieva, E., Björk-Eriksson, T., Alborn, A. M., Nordborg, C., Peterson, D. A., & Gage, F. H. (1998). Neurogenesis in the adult human hippocampus. Nature medicine, 4(11), 1313-1317.
  7. Van Praag, H., Kempermann, G., & Gage, F. H. (1999). Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nature neuroscience, 2(3), 266-270.
  8. Van Praag, H., Shubert, T., Zhao, C., & Gage, F. H. (2005). Exercise enhances learning and hippocampal neurogenesis in aged mice. The Journal of Neuroscience, 25(38), 8680-8685.

 

Featured image from: http://www.franklandlab.com/?page_id=302

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