Neuroplasticity with Michael Merzenich

A friend and fellow PT, Jon Newman, recently sent me a link to a TED video released for public viewing only in April, it seems - Michael Merzenich on rewiring the brain. If you have ever wondered what neuroplasticity is, check this out. It runs about 23 minutes and I guarantee you'll come away with a deeper grasp of what the brain is and does.

Here is an excerpt I thought was particularly interesting:

"Now, one of the characteristics of this change process is that information is always related to other inputs or other information that's occurring in immediate time, in context. And that's because the brain is constructing representations of things that are correlated in little moments of time, and that relate to one another in little moments of successive time. The brain is recording all information and driving all change in temporal context.

Now, overwhelmingly, the most powerful context that occurred in your brain, is "you". Billions of events occurred in history that are related in time to your "self" as the receiver, your "self" as the actor, your "self" as the thinker, your "self" as the mover.

Billions of times, little pieces of sensation have come in from the surface of your body, that are always associated with "you," the receiver, and result in the embodiment of "you". "You" are constructed. Your "self" is constructed from these billions of events; it's constructed, it's created in your brain and it's created in the brain by physical change. This is the marvelously constructed thing that results in individual form, because each one of us has vastly different histories, and vastly different experiences, that drive into us this marvelous differentiation of self, of personhood."

I love this video. It makes me glad I picked the sort of work I did. I quite like the idea that when I put my hands on someone else, I'm helping them learn more about who they are, helping that brain add to its construction of "self" outside of a pain construction (if I'm careful, and I am). I like that I'm adding more "little pieces of sensation" to their temporally correlated process of embodied self, minus nociceptive input, i.e., more "danger" signals. Yeah, I can live with that.

I also like the idea that I learn more about/add to my own self-construct at the same time, as "little pieces of sensation" from my own skin (on my hands) enters my brain and is temporally correlated to what is already in there.

What is already in there? Circuitry routes, billions of neurons, receptor sites on them (lots and lots of receptors that can change to different ones, alter what they are sensitive to, thanks to "synaptic plasticity") and transmitters. There are convergence zones and arborizations, ascending and descending fibers, switchback and feed forward stations, and lots of somatotopic representational areas (brain maps of body parts). There is brain behaviour, and parts or areas that light up for pain as well as for other functions on fMRI, a vastly complex ecosystem, embedded within another outer ecosystem called the "body," with which it is completely integrated, both of which must exist co-mingled and learn to help each other within the greater outer planetary ecosystem, via a construct called "self."


Additional Reading

1. Michael Merzenich's TED bio
2. A page from my website, About Pain


Older blogposts on Neuroplasticity

1. Neuroplasticity (Dec 11, 2007)
2. Learning (Dec 12, 2007)
3. History of Neuroplasticity (Dec 12/2007)
4. Paradigm (Dec 16, 2007)
5. About mirror therapy (Dec 16, 2007)
6. Get your game on, ease your pain (Dec 17, 2007)
7. The devil is in the details (Dec 18, 2007)
8. A few types of Learning (Dec 18, 2007)
9. Cart ruts: More about UN-doing something (Dec 29, 2007)
10. And it's about brain parts: like hippocampus (Dec 30, 2007)
11. Function only (January 15 2008)
12. Smart prosthetics, smart nerves, smart brains (February 10, 2008)
13. Nervous System Basics VIII: PLASTICITY (May 10, 2008)
14. More about neurogenesis (June 7, 2008)
15. "Dialogues in Clinical Neuroscience" online (August 23, 2008)

Synapse Proteomics

Lily Tomlin, in her comedic role as Trudy the bag lady, in the 1991 film Searching for Signs of Intelligent Life in the Universe, mentioned that she thought she likely suffered from a few "lapses in the synapses."

In all seriousness though, both Deric at Mindblog and Mo at Neurophilosophy have referred recently to work being done on synaptic complexity.

1. Deric's post, Increasing complexity of nerve synapses during evolution refers to this Nicholas Wade article in the New York Times, Brain Power May Lie in Complexity of Synapses, which looks at the possibility that the more complex the synapses are, the more brain power there is likely to be.
(Image from the Nicholas Wade NYT article, originally from the journal Nature Neuroscience.)
The NYT article looks at this paper, Evolutionary Expansion and anatomical specialization of synapse proteome complexity by Emes RD, Grant S, et al.

2. Meanwhile, Mo at Neurophilosophy wrote this blogpost: Synapse proteomics & Brain Evolution about the same paper.
.........................................

In the first part of a series of posts here called Nervous System Basics (see Part I), I wanted to draw attention to the fact that there are 100 billion neurons, 1-10 trillion glial cells, and 100 trillion chemical synapses.

This is just so hard to imagine (i.e., form a mental construct about). And those are just the numbers associated with the complexity due to numbers of microscopic-sized physical structures. Now add large numbers of complexities in the synapses themselves, at a molecular (beyond ordinary microscopic-sized) order of magnitude, and you might catch a glimpse of how complex our brains truly are.


HERE ARE SOME TAKE HOME POINTS

1. It's not just about brain size or numbers of neurons:
From the Wade NYT piece:

"A human brain... is three times the volume of a chimpanzee’s... (however) in fact the synapses get considerably more complex going up the evolutionary scale, Dr. Grant and colleagues reported online Sunday in Nature Neuroscience. In worms and flies, the synapses mediate simple forms of learning, but in higher animals they are built from a much richer array of protein components and conduct complex learning and pattern recognition..."

(From Mo's Neurophilosophy post:)

"a new study which used bioinformatics to compare the synapses of distantly related species suggests that size may not be the most important factor in human brain evolution after all. Instead, the new findings, which were published online in Nature Neuroscience on Sunday, suggest that it is an increase in the complexity and number of synapses that was crucial for the emergence of complex behaviours and cognition."

2. Each synapse has a role in adding complexity and therefore brainpower:

"If the synapses are thought of as the chips in a computer, then brainpower is shaped by the sophistication of each chip, as well as by their numbers. “From the evolutionary perspective, the big brains of vertebrates not only have more synapses and neurons, but each of these synapses is more powerful.." (- Wade quoting Dr.Grant)

(From Mo's post:)

"On the receiving end of the synapses of mammals, immediately beneath the membrane, there is a dense network of proteins called the postsynaptic density (PSD). The PSD contains more than 1,000 proteins, which can broadly be divided into 3 different classes: the components of around 12 parallel but converging signaling pathways.."

3. Synapses preceded nervous systems: (Wade again:)

"He included yeast cells in his cross-species survey and found that they contain many proteins equivalent to those in human synapses, even though yeast is a single-celled microbe with no nervous system. The yeast proteins, used for sensing changes in the environment, suggest that the origin of the nervous system, or at least of synapses, began in this way."

4. Synaptic problems ("lapses in the synapses") may be responsible for mental disorders (Wade again:)

"The roots of several mental disorders lie in defects in the synaptic proteins, more than 50 of which have been linked to diseases like schizophrenia, Dr. Grant said."

5. Synapses might "evolve" by 'tweaking' themselves? :

In Mo's post, there is a link to this page, on postsynaptic density or PSD. In it is stated the definition; "The postsynaptic density is a multiprotein complex containing membrane proteins, signaling molecules and core PSD proteins." Mo says,

"The PSD contains more than 1,000 proteins, which can broadly be divided into 3 different classes: the components of around 12 parallel but converging signaling pathways, with the components of each one clustered to form an enormous macromolecular complex; the cytoskeletal and scaffolding proteins which tether the complexes to precise locations at the membrane, in close proximity to the receptors which activate them; and the enzymes which regulate the movements and functions of the complexes and their individual components within the membrane.

The regulatory enzymes act by making minor modifications in the structure of the signaling pathway components. One apparently ubiquitous form of modification involves the addition of a small molecule called a phosphate group to a specific site on the target protein. This process, phosphorylation, is catalyzed by enzymes called a kinases. It is reversible, and acts like a switch - the phosphate groups can be removed by another group of enzymes called phosphatases, and the addition or removal of a phosphate group activates or inhibits a target protein.

These signaling pathways are incredibly complex - the enzymes all act on multiple targets, and differ in their effects on each. Furthermore, they are subject to the same regulatory mechanisms as the proteins they regulate. They too can have phosphate groups or other small molecules added or removed, and in some cases, activate or inhibit themselves by catalyzing modifications of their own structure."

(This is really clear, and I'd like to thank you Mo, for being such a good writer on such a difficult topic that even a regular person like me can catch a glimpse of some immense implications...)

6. Proteomics (i.e., the study of proteins) might help researchers unravel synaptic mysteries and reveal more about how the brain "works": (Mo again:)

"The interactions between these signaling pathways are very poorly understood, largely because researchers were until recently only able to investigate one or two of the components at any one time. This is where proteomics comes into its own, because it allows for simultaneous analysis of hundreds or thousands of molecules, enabling researchers to begin teasing apart the pathways and networks instead of plucking individual components out one at a time."

Additional Links/Reading:
1. Genes to Cognition program headed by Seth Grant
2. Grant S; Organization of brain complexity - synapse proteome form and function (2006, open access)
3. Genes2Cognition
4. Grant S; The synapse proteome and phosphoproteome: a new paradigm for synapse biology (2006, 5-page pdf)
5. Hensch TK, Fagiolini M; Excitatory-Inhibitory Balance: Synapses, Circuits, Systems (2003): Chapter 1, The Organization and Integrative Function of the Post-Synaptic Proteome, is by Grant S et al.
6. Ziff EB; Getting to synaptic complexes through systems biology (2006)
7. Short (5 minute) YouTube video: Neurons and Neuro-transmitters
8. Press release June 2009, from the Sanger Institute where Seth Grant works: Origins of the Brain: Complex Synapses drove brain evolution
9. Emes R and Grant SG et al; Evolutionary expansion and anatomical specialization of synapse proteome complexity, Nature Neuroscience, June 2008, open access 8-page pdf