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Dr. Michelle Freund, NIMH Project Officer on the significance of CLARITY

Project officer Michelle Freund, Ph.D., of the NIMH Division of Neuroscience and Basic Behavioral Science, explains the significance of CLARITY, a breakthrough method for analyzing the brain.


Michelle Freund, Ph.D.: The brain initiative recently announced by the White House is really designed to facilitate innovative strategies to better understand the brain. And in order to do that we need new technologies. CLARITY is a great example of the type of new technologies that will enable future brain studies.

So prior to this technology, scientists used methods where they would take thin slices of the brain. They would put these on glass slides, process them with antibodies, which illuminate what chemicals are there. And then they would have to use a microscope to study which transmitters are in which locations. Unfortunately, you can’t see the structure of a neuron in a brain slice.

So with this technology, they’re able to look at the entire neuron in a three dimensional volume. And with this three dimensional structure intact, you can see where the neuron starts and what brain region it projects to. In slices, you can only see what’s in the position where you started. And what this technology will allow is to do is not only study what molecular or single elements of a cell are located in a neuron, but how those communicate with other elements in the brain.

So in the recent publication by Deisseroth and colleagues, they describe not only the ability to look at animal models – or whole brains of animals – but also the ability to look in human brain. So in a post-mortem brain from a child suffering from autism, they were able to trace neuronal projections from a significant volume of tissue. They’re also able to use the technology to stain for neurochemicals located in that brain region. And the potential for this type of research is great for understanding how disruptions in neural circuitry are involved in disorders. It has really transformative potential.

The technology shows us in the video an area of the brain that’s involved in memory, the hippocampus. And this video shows the neurons that are involved in processing memory, where they project, and what neurotransmitters, or chemicals are contained in those neurons. And it shows this in three dimensions, so you see not only where they start and where they project and how they might interact to form memories.

The video through an entire mouse brain shows us how neurons are connected. So the neural circuitry – which neurons project to which areas in the brain, how they might be involved in giving commands to execute certain functions that we know about from physiology studies, but we don’t actually know how they connect to each other. This technology allows you to bring those together.