Researcher creates neurons that light up as they fire

[sourced from PhysOrg.com]

In a scientific first that potentially could shed new light on how signals travel in the brain, how learning alters neural pathways, and might lead to speedier drug development, scientists at Harvard have created genetically-altered neurons that light up as they fire.

The work, led by John L. Loeb Associate Professor of the Adam Cohen, and described in  on Nov. 28, involved using a gene from a Dead Sea microorganism to produce a  that, when exposed to the electrical signal in a neuron, fluoresces, allowing researchers to trace the of signals through the cell.

“It’s very exciting,” Cohen said of the research. “In terms of basic biology, there are a number of things we can now do which we’ve never been able to do. We can see how these signals spread through the . We can study the speed at which the signal spreads, and if it changes as the  undergo changes. We may someday even be able to study how these signals move in living animals.”

To create the light-up , Cohen and his team infected  that had been cultured in the lab with a genetically-altered virus that contained the protein-producing gene. Once infected, the cells began manufacturing the protein, allowing them to light up.

“The way a neuron works is it has a membrane around the whole cell, sort of like a wire and insulation, except in a neuron the membrane is an active substance,” Cohen said. “Normally, the inside of the cell is negatively-charged relative to the outside.

“When a neuron fires, the voltage reverses for a very short time, about 1/1,000th of a second,” he continued. “This brief spike in voltage travels down the neuron and then activates other neurons downstream. Our protein is sitting in the membrane of the neurons, so as that pulse washes over the proteins, they light up, giving us an image of the neurons as they fire.”

The research has the potential to revolutionize our understanding of how  move through the brain, as well as other tissues, Cohen said.

“Before, the best way to make a measurement of the electrical activity in a cell was to stick a little electrode into it and record the results on a volt meter,” he said. “The issue, however, was that you were only measuring the voltage at one point, you weren’t seeing a spatial map of how signals propagate. Now, we will be able to study how the signal spreads, whether it moves through all neurons at the same speed, and even how signals change if the cells are undergoing something akin to learning.”

Another limitation of using electrodes, Cohen said, is that the process tends to kill the cells relatively quickly, making it impossible to study processes that take place over time. His new process, however, opens the door to studying the effects of growth and development on neurons, or to monitor how stem cells develop.

Being able to track the electrical pathways in cells also holds practical applications, Cohen said, particularly when it comes to the development of new drugs or other therapies.

“Many, many drugs target ion channels, which are important proteins in governing the activity of the heart and brain,” he said. “Right now, if you want to test a compound designed to activate or inactivate a particular ion channel, you have to culture the cell, test it with an electrode, then add the drug and see what happens. This is an extremely slow process – it typically takes an hour or two for each data point.

“Now that we can do it optically in the microscope, we can test the efficacy of a drug on a cell in a few seconds. Instead of testing one compound or ten compounds, we can try to test thousands or even hundreds of thousands. We can test different conditions, different mixtures – it will increase the throughput for testing new drugs.”

The process may even open new research avenues for those studying genetic conditions ranging from depression to heart disease.

Using stem cells, researchers can culture cells in the lab that are genetically identical to a patient known to carry a genetic predisposition to a particular condition, then study how signals move through those cells.

Provided by Harvard University (news : web)

Advertisements

12 comments

  1. Truly amazing research. Light is Fantastic! There is a very active research in use of light phenomena to study and illuminate never before considered vantage points. It truly reveals all of the physical world to us whether at the cosmological scale or atto-scale!

    1. Can I take this as an official quote from you for the careers forum…? It will help me convert those medics, economists, biologists, and every other non-physicists into the awe-inspiring “physics student collective”… resistance is futile! :)

      Can you tell me how and where the memory is store in the brain… please? I started reading Eric Kendel’s book but always get side tracked into reading something else. The brain is supposed to have almost infinite long term memory is that right?

      1. Lol, yes you can take this as an official quote from me but I must warn you that equilibrium unbalance between physics and biology can occur at any time. At present, the equilibrium has shifted towards physics but equilibrium can tilt its direction at any point in time. Beware!!!

        Short term memory is formed in an area of the brain called the hippocampus (sea horse shaped), its a subcortical structure meaning that you have to remove the overlying cortical tissue called the operculum to view this region found deep in the brain. Memory formation occurs through a process called Long term potentiation (LTP). Once these memories are consolidated into long term memory, they are stored elsewhere, in the cortex.

        Alot of the stuff we know about the brain comes from pathological and lesion studies. For instance, in the case of Broca’s area (area involved in speech formation) and Wernicke’s area (area involved in speech understanding) were discovered in patients who had degenerated these areas and they were unable to understand or form speech. Then it was worked out that due to the degeneration of these specific areas, speech functionality is impaired. In the case of Alzheimer’s disease, hippocampus is one of the regions affected very early in the disease process, hence Alzheimer’s disease patients cannot form new memories. But their long term memory still remains intact, which suggests that the memory is stored elsewhere other than the hippocampus, at least bulk of it. Its in the mid-late stages of the disease that they begin to lose information of their past life. However, memories with emotional links are remembered for longer since they are quite strong. Brain is very powerful and it can store alot of information. You also have cognitive reserves which are expanded depending on your diet, healthy lifestyle and education etc. Brain has alot of capacity, hope I answered your question

      2. Hehe. Perhaps.

        Jazaak’Allah for the answer. But i am still not clear,how the memory is stored? How is information stored in a neuron or a collection of neurons? Because your description tells us that its localised to certain portions, but not how it is achieved by the brain. Also memory is formed with sensory input but also non-sensory input. How is the interaction of such inputs used to create a memory at the neuron level? For example, the smell of pancakes and maple syrup might remind me of a time when i was young, but the information of relating to the smell… how is it stored? furthermore, attached to that memory is an image that was created from no doubt neurons coming from my eyes, how was this stored? Then include other sensory inputs to this whole memory of me eating a maple syrup on pancake.

      3. I am not sure as to how information is stored in a neuron or collection of neurons, Naveed Sb or Anas might be able to help. Sensory integration of smell, taste etc occurs in the parietal association cortices but I dont know how inputs are used to create memory at a neuronal level, unfortunately. A very good question, can someone please answer the question as I have now become a little restless to know the answer.

        For long term potention, NMDA receptors (a type of ionotropic glutamate receptors) and other receptors are activated. Acetylcholine also is responsible for enhancing learning and memory. I know that the neuron probably undergoes electrical and chemical changes to store memory, thats how much I know unfortunately. I can tell you about the different kind of memories that we form, implicit and explicit etc.

  2. Neurons communicate with each other at gap junctions called synapses, and I think it is here that the memory is stored. Synaptic connections are formed and modified in response to learning of new stuff etc.

    1. I am speculating but, let me ask another questions. What do we mean by memory? Wikipedia’s answer is that it is the system’s ability to store, retain and recall information or data. Now what is the brain storing, retaining and/or recalling? A series of neural pathways, electrical/chemical signal or something else? lets say upon smelling a familiar smell electrical/chemical signals are generated from the nerves in the nostril (not sure but lets assume this is what happens, which through the nervous system are sent through a specific pathway. Lets call this path A. Now if i smell this smell again will the electrical signal travel the same path A? resulting in the “familiarity sensation” of the smell?

      What about the end point of this neural pathway A? I am uncertain but would not the gap junctions, which your suggesting may store information, would be chemically governed? This causes a lot of problems.

      Alternatively, could the memory storage be dynamic. Lets say we have a memory call it x, made up of myriad of electrical n|e> and chemical signals m|c> where n,m are any integer describing the relative strength of the signal. So as an example,

      x = 1|e> + 5|c>

      So to reiterate, in this model, for memory x to be recalled an electrical signal of strength 1 and a chemical signal of strength 5 need to be generated otherwise that memory will not be recalled. This way once a memory pathway is made, it can be recalled anytime, as long as the right electrical /chemical signals are generated.

      Consequently, could it be that electrical/chemical signals are moving from one neuron to another. As more memories are created more neurons are formed or more precisely the key is not in the neurons itself but the neural pathways that are created.

      But this brings up even more questions… Naveed Sahib (our theoretical neuroscientist) can you please help. I too, like Azhaar, can’t stop thinking about it…Need to know!

      1. I am quite sure that electrical/chemical signals are moving from one neuron to another all the time and use synapse as a means to communicate with each other. Synaptic connections and the neural pathways are key here for me but I do understand your point about chemical reactions as well.

        There isnt just one kind of memory, these memories have to be divided into implicit and explicit memory. These have further classifications. Implicit memory can be recalled without conscious thought whilst explicit memory is something that requires a conscious mind to be recalled – ‘Memory is the process by which knowledge is encoded, stored and later retrieved’. The problem is that I am a biologist, my main focus is on the functionality of neural systems but I am very interested in these kind of discussions.

        Synaptic connections are formed once a memory of something is formed. Upon re-encounter of the same memory, our synaptic connections are strengthened which increases our ability to recall stuff that we have revised. In other words, the neural pathways are further consolidated. The good thing about our neurons is that they undergo plasticity, highly adaptable and one’s neurogenesis (production of neurons) is based on the extent of learning he/she is exposed to and this increases the neuronal connectivity of the brain. In cases of dementia, some reports suggest that neurogenesis is inhibited, therefore the neuronal connectivity is on the decline, hence the memory and other cognitive functions.

        I think I am going off the topic now, so I will let others intervene at this stage!!!

      2. Fascinating… this is starting to make sense, well sort of. So let me get this straight…

        By themselves the neurons and the various electrical/chemical signals mean nothing. Nor do they store any information of any sort. Correct?

        But in conjunction they can store, retain and recall information whether explicit or implicit. Which is achieved through the plethora of neural pathways that are present in our brain. Like a polymer chain, neurons are connected to each other through a synaptic connection (i think its chemical diffusion through a gap junction, right?), they do not store information, right?

        Information is retrieved when the same neural pathways through the same synaptic connections are made. The more these connections are visited by the electrical/chemical signals the stronger and everlasting the connection becomes.

        So memory in the brain is not a thing we can pin point, but is latent in these neural pathways and connections! Sounds plausible enough, we should have some experimental evidence to back this…

        Next Question: How can our minds have the ability to recall a specific memory? How does it do that? How can it access a specific memory? How do these neural pathways are fired without even us thinking about it?… i have an idea, but for now its too long to explain and i gotta go…

Discuss

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s