BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: optogenetics

Environmental Cues Can Trigger Planned Movement and Advance Studies of Motor Disorders

A group of scientists from different universities, including Dr. Hidehiko Inagaki, Dr. Susu Chen, and Dr. Karel Svoboda, came together to understand how cues in our environment can trigger planned movement. Neurons in the human brain are active with diverse patterns and timing. The Motor cortex is responsible for the control of movement. The patterns of the motor cortex differ in the phases of movement. The transitions between these phases is a critical part of movement. The brain areas controlling these transitions were a mystery.

To identify the parts of the brain controlling these transitions the group of scientists performed their research on mice.They recorded the activity of neurons in a mouse’s brain when doing a triggered movement task. Researchers found brain activity taking place directly after the go cue and between the stages of movement. This brain activity came from a circuit of neurons in the midbrain, thalamus, and cortex. To determine whether this circuit was a conductor or not the scientists used optogenetics. Through the use of optogenetics Dr. Inagaki and his colleagues were able to identify a neural circuit critical for triggering movement in response to environmental cues. Dr Inagaki says that “We have found a circuit that can change the activity of the motor cortex from motor planning to execution at the appropriate time. This gives us insight into how the brain orchestrates neuronal activity to produce complex behavior.

Figure-1

Not only is this important for the use of knowing more about the brain but it also helps to advance studies of motor disorders, such as Parkinson’s disease. By adding environmental cues to trigger movements it could drastically change the mobility of patients.

In Ap Biology class we learned about cell communication. Neurons communicate with each other by releasing specific molecules in the gap between them, called the synapses. The sending neuron passes on messages through neurotransmitters that are picked up by the receptors of the receiving neuron.

Could A Simple Plant Principle Help Us Better Manipulate The Brain?

The researchers and scientists at Weill Cornell Medicine are working on a family of light-sensing molecules with great haste. This research can advance the very complicated field of optogenetics. There are light-sensitive proteins that play a very important role in the field of biology as a whole. This has to do with topics ranging from its use in photosynthesis to even our own vision. In photosynthesis these proteins are how plants are able to absorb the photons given off from the sunlight and react by using it as an energy source. Most of the information on these types of proteins are from the specific protein bacteriorhodopsin, which is seen in these photosynthetic reactions. However we can only study this protein to a certain point given the technology we have which has lead researchers to a road block. This new study which is being called; line-scanning high-speed atomic force microscopy, will help pass this block. 

Rat primary cortical neuron culture, deconvolved z-stack overlay (30614937102)

 

The problem that was occurring when studying this field was that the tracking of activity of individual molecules was too slow to see the protein actually change, for example how bacteriorhodopsin reacts to light. The new approach involves sacrificing the image detail of the altering molecules for a much faster frame rate. It is as if one was taking blurrier pictures of a horse in order to capture its entire journey. According to Dr. Perez Perrino they are tracking the protein every 1.6 milliseconds in order to speed of bacteriorhodopsin in its natural, wild-style habitat. As a result of light it will switch between open and closed states. With this new method of imaging they have concluded that the transition to the open state and the its duration always happen at the same speed. However the molecule remains in the closed state for a longer period of time as the light increases.

Optogenetics begins to play a role because researchers in this field insert genes for light-sensing molecules in neurons or other cells, causing them to alter the cell’s activity. This work could potentially help us control the brain in ways we could never imagine. This could lead to eventually treating neurological diseases in the near future.

While studying the brain there arises the need to activate or inhibit certain cells. The most common process for doing this in the past was optogenetics. Optogenetics is the use of light to activate or inhibit cells. While optogenetics is very precise, it has some drawbacks and limitations. Light is scattered in the brain and to reach deep in the brain scientists usually insert a fiber optic cable which is highly invasive. This practice is still used today, but there has been a new development: sonogenetics. Researchers at the Salk lab have been working on this new technique. Sonogenetics use sound waves, low-frequency ultrasound waves to be more specific, to activate the neurons. This new method allows scientists to reach neurons deep in the subject’s brain without having to perform a surgery to implement a fiber optic cable. It also has the potential to have no effect on the surrounding neurons. In the Salk laboratory, the scientist used worms to study the use of sonogenetics. Worms would normally be impossible to work with as performing surgery to implement a fiber optic cable is nearly impossible, but with the use of sonogenetics the scientist were able to activate certain neurons. The sound waves were aided by microbubbles outside the worm that oscillated in size in conjunction with the wave. The scientist then discovered TRP-4, an ion channel which can be affected by the sound waves. They found that the sounds waves along with the microbubbles can open these channels and activate the cell. Though this process they activated cells that would normally not have been activated by ultrasound. Although it all sounds very promising, sonogenetics has only been used on Caenorhabditis elegans neurons.

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A picture of Caenorhabditis elegans

 

https://en.wikipedia.org/wiki/Caenorhabditis_elegans#/media/File:CelegansGoldsteinLabUNC.jpg

The next step in the research would be to get the sonogenetics to work in a mammal’s brain. This could potentially lead to therapies that are non-invasive for humans. However, how comfortable would you feel with doctors using sound waves to control neurons in your brain? Sonogenetics sounds very promising and contains a lot of upside, however, the research is not far enough along yet to completely tell.

 

Original Article: http://www.salk.edu/news/pressrelease_details.php?press_id=2110

 

For More Information: http://dujs.dartmouth.edu/news/sonogenetics-the-latest-in-mind-control#.VhMJimRViko

 

Editing the Brain Using Epigenetic Tools

Epigenetics is a huge part of our life and influences us in ways we may not be aware of. Did you know that it is impossible to create and save new memories without epigenetic tags? The brain is heavily reliant on Epigenetics to do its functions, and this makes it a huge topic of research to figure out the ways in which the epigenetics of the brain could affect certain diseases or memory. Recently special epigenetic molecular tools have been created that can erase specific epigenetic markers throughout the genome. The possible effects these tools could have on the curing of diseases of the brain or psychological ailments are tremendous.

These “epigenetic editing” procedure use either CRISPR (clustered, regularly interspaced, short, palindromic repeats) or TALE (Transcription activator-like effector) systems of modification. These systems can carry an Epigenome modifying enzyme and deliver it a specific site they are programmed to go to. This allows researchers to target very specific epigenetic changes and either shut them down or turn them on and possibly determine their correlation with certain ailments of the brain. “We’re going from simply being able to observe changes to being able to manipulate and recapitulate those changes in a controlled way,” Day said. This quote from Day, one of the researchers of this project, shows that we advance from only being able to observe epigenetic influences on the brain, to being able to manipulate and control them to potential aid us in combating diseases.

Researchers can catalog all of the epigenetic changes involved in forming and preserving a new memory. If we are able to track these epigenetic changes, then could we implant memories in to a person’s mind, by copying similar epigenetic changes? These researchers where also able to trigger not only the place where epigenetic change happens, but also the exact time using optogenetics. This form of using light to control neurons allows researchers to use the TALE system and a light switch apply epigenetic change to very specific brain regions or cell types.

One of the final goals of this research is to eventually be able to use epigenetic as a form of therapy to benefit PTSD, depression, schizophrenia, and cognitive function using the ability to alter epigenetic marks. This can also be used in a similar way to silence mutated genes that are damaging the cells or the body as whole. This form of using TALE and CRISPR to alter epigenetic tags creates a lot of hope for PTSD, depression, schizophrenia, Alzheimer’s, Parkinson’s, Huntington’s and other similar disease treatment options.

Sensing neuronal activity with light

neurons

Researches have recently developed a tool that may help in mapping the neural networks of living organisms using light. Observing these electrical signals of neurons can lead to numerous advancements in our understanding of neural circuitry.

In a collaborative study between Viviana Gradinaru, Frances Arnold and Barbara Dickinson, they developed a method to sense neuronal activity with light. These researchers used a protein named Archaerhodopsin (Arch) and exploited its light responsive qualities. They were able to optimize Arch through a process known as directed evolution. Using this method they created a variant of the Arch protein, called archer1 that acted as a voltage sensor under a red light and an inhibitor under a green light, while generating a light intensive enough to detect. When this protein acts as a voltage sensor it can show which neurons are active and synaptically connected and which aren’t under certain stimuli.

These researchers were able to test Archer1 in the worm C. elegans, which was chosen for its near transparent tissue that made it ideal for observing the luminescent protein. This was the first place they were able to observe the circuits of the neurons light up if they were expressed and dim down if they were repressed. For future studies they hope to make Archer1 bright enough to be detected through opaque tissue and accurate enough to detect voltage changed in more complex, behaving mammals. This study can prove to help us in our understanding of neural networks.

Original papers:

http://www.pnas.org/content/111/36/13034

http://www.nature.com/ncomms/2014/140915/ncomms5894/full/ncomms5894.html  (You can only read abstracts; you have to pay to read the full text)

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