Incredible drug breakthrough for children with fatal muscle disease

This week, while reading the New Scientist I came across this exciting article. For many children born with genetic disorders such as spinal muscular atrophy or Huntington’s disease, the prognosis is never too good. With spinal muscular atrophy, children rarely survive past the age of two. This particular disease is caused by the progressive degeneration […]

How does the immune system know how to raise the body’s temperature in response to an infection?

Answer by Tirumalai Kamala: Fever results not from the immune system alone but from immune system plus hypothalamus. Infections typically target specific cells, tissues and organs. This is called Tissue tropism. Some pathogens have a broad range, others narrow. Since infections can target every organ from skin, GI tract and lungs to heart and brain, […]

Bending your brain: What is neuroplasticity?

Your brain is a muscle. Likewise with all other muscles in your body, if you don’t use it, you’ll lose it. Neuroplasticity is the idea that your brain is flexible, which can adapt as a response to experience: It changes constantly to meet the demands of the body. It continuously reorganizes itself.

For example, after a stroke the brain is capable of transferring the cognitive abilities from one lobe to another! Functions that are usually associated with the damaged area are relocated to healthy areas!

Another example- if the corpus callosum (the link between the two hemispheres) is cut, and one hemisphere is removed, the functions of the removed half may be transferred to the remaining hemisphere.

One common example of neuroplasticity is, of course, learning and developing memories. Neural pathways are surreptitiously being revamped and re-organised, accounting for new experiences, information and memories.

I am sure we can all concur that learning is far easier for children than it is for adults. At a young age, we learnt to walk, talk, comprehend hand gestures, begin learning simple skills at school etc. Why is this? In children, the memory making process occurs much more profoundly than in adults. At birth, an infant will have around 86 billion neurons, and the brain will increase in size by a factor of up to 5 by adulthood.

By the age of 3, a child will have around 15,000 synapses per neuron. However, contrary to what you may believe, an adult will have around half this value of synapses per neuron. This seems bizarre, but it is all due to a process called synaptic pruningThis is the process of synapse (the connection between neurons) elimination, leaving your brain with less junctions. Why does this happen? During the transition into adulthood, some connections are strengthened (those which are used profusely) and the unnecessary neuronal structures are eliminated. This makes some sense, as why would you keep pathways which are not used? Maintaining these connections would waste crucial energy. Alternatively, this energy could be used to strengthen those pathways which are vital in everyday life. In addition, as you will know, young children are incapable of understanding complex structures. Try explaining differentiation to a 5 year old. Therefore, the brain must adapt and reconfigure itself to be able to understand these more complex and demanding systems. The simple associations formed during childhood (the tooth fairy, santa…) are thought to be replaced by other more ‘mature’ forms. Thus, as you grow your brain is essentially adapting and changing to your environment, fine-tuning its connections. So, use it or lose it! The main methods of synaptic pruning are apoptosis (cell death) and pruning. In apoptosis,  the neuron is killed along with all its associated connections. In pruning, the axon retracts from the inessential synaptic connections.

So how do you ‘use’ it? What is the mechanism behind learning? The answer would be Long Term Potentiation (LTP). This is the hypothesised theory of memory storage.

Long Term Potentiation (LTP)

On a normal post-synaptic cell, you have receptors called AMPA and NMDA. These receptors are activated after the binding of the neurotransmitter glutamate, which is released on the arrival of an action potential. AMPA receptor is permeable to Na+. NMDA is also permeable to the ion Na+, but has a higher permeability to Ca2+. In addition, this channel is blocked by the chunky Mg2+ ion. When the channel is blocked by magnesium, no calcium can diffuse through.

Lets pretend that we are studying for a test.  Since this is the first time we have picked up our book, low frequency action potentials will be generated. Glutamate is released as the neurotransmitter from the pre-synaptic neuron, which binds to receptors on the post-synaptic neuron. This opens the AMPA receptors, causing a slight depolarization of the membrane as sodium ions enter. The NMDA receptors are also opened, but no sodium can diffuse through due to the magnesium blocking its path.

Lets pretend we pick up our book again the next day to revisit what we’ve learnt. Now, a higher frequency action potential is generated. The AMPA receptors are kept open for longer, so more sodium enters the cell. This causes a large depolarisation, as the sodium accumulates and the neuron grows more and more positive. Now that the post synaptic cell is depolarised, the positive magnesium is no longer repelled into the channel by the positive extracellular environment. Rather, it is repelled out of the channel. This allows the influx of calcium, depolarising the cell even more. Accordingly, NMDA receptors are known as coincidence receptors, since they require a pre-synaptic and post-synaptic event to open their channels.

Once this second stage is reached, the memories begin to assemble. The calcium inside the neuron binds to respective proteins. This causes a cascade of events, resulting in new AMPA receptors being inserted into the neuron cell membrane. Now there are extra AMPA receptors to allow further LTP. However, this early stage only last for a few hours and requires brief calcium increase.This is why recalling information is easy after an hour, but you will almost certainly forget it the next day.

How to get those facts to stick 

Once you pick up the book again, the magic beings to unravel. Prolonged depolarisation allows a larger influx of calcium ions. These bind to the proteins, which are involved in transcribing genes which code for the production of AMPA receptors. If there is more transcription, there is more gene expression, so more synthesis of the AMPA proteins, resulting in more receptors present on the plasma membrane. In addition to this, there is an increase in growth factor proteins. This creates further synapses for that neuron, leading to much stronger connections between neighbouring neurons.

This process allows you to recall and remember all those facts weeks after you have revised. No matter how much we hate it, revision is important!

So, as you have seen the brain is forever evolving and adapting to our environment. Whether this is building and reinforcing connections, or obliterating useless ones, our brains are active and unstoppable machines chugging relentlessly through all the information we give it.

Finally, here are a few key points to note about neuroplasticity:

  1. It can vary by age;while plasticity occurs throughout the lifetime, certain types of changes are more predominant during specific life ages.
  2. It involves a variety of processes;plasticity is ongoing throughout life and involves brain cells other than neurons, including glial and vascular cells.
  3. It can happen for two different reasons;as a result of learning, experience and memory formation, or as a result of damage to the brain.
  4. Environment plays an essential role in the process, but genetics can also have an influence. – This is a fantastic site about the brain