Neurology Central

Understanding the brain with sonogenetics: Interview with Sreekanth Chalasani

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Emerging technologies for basic neurological research have had – and will continue to have – a significant impact on the progression of the field, from understanding the complex neuronal circuits of the brain to identifying new opportunities and approaches to treatment. Most influential of these has perhaps been the birth of optogenetics, utilizing light waves to manipulate neurons. However, new approaches to this mechanism are currently developing, which could provide even more flexibility. We talked to Sreekanth Chalasani from the Salk Insitute of Biological Studies (CA, USA) to find out more about their early work into the use of ultrasound for nerve manipulation, a technique they have termed ‘sonogenetics’.

What are the current research focuses in your lab?

The research in our lab is focused on understanding how animals generate behaviors. We know that specialized sensory neurons gather relevant information from the environment, which is then integrated with signals from internal tissues and prior experiences. Animals combine all of this information to generate an appropriate behavioral response, enabling them to maximize their survival.

To understand how this works, you need a model where you can identify all of the neurons that participate in generating the behavior; that is, all the neurons that are required for detecting the sensory input, integrating the internal state signals, the prior experience and generating the appropriate behavioral output. This level of information is currently only available for simple invertebrate systems. For example, the nematode C. elegans has only 302 neurons in its nervous system, which are connected by known electrical and chemical connections. Here, you can trace a complete connectivity map all the way from input sensory neurons to the output muscles– this opportunity does not exist in other animals yet.

Are there currently efforts to create these connectome maps for any other organisms?

There is a lot of emphasis on creating the connectome map for mice and humans. The blue brain and human brain project directed by Henry Markram (Ecole Polytechnic Federale de Lausanne, Switzerland) aims to develop a map of the mouse and then the human brain. Researchers at Janelia Research Campus near Virginia (USA) are also trying to map the brain of the fruit fly Drosophila. But C. elegans is so far the only animal model that has a complete connectome map.

What are the advantages of utilizing such simple model organisms for neurological research?

C. elegans research has a number of advantages: they have a similar number of genes as humans, it is much easier to manipulate them and their generation time is just 3 days. We can identify all of the 302 neurons simply by position and manipulate them individually. Also, we find that neurons in C. elegans that are similarly connected have similar functions. For example, we found that a connectivity motif of three similarly connected neurons is used to enhance contrast in both C. elegans and humans. Evidence of neural circuit functions being conserved such as this justifies using simpler systems to study brain function.

Of course, we are also finding other things that are conserved, for example we know that genes that are required or associated with neurological conditions in humans have similar functions in simpler systems. Neurexin and neuroligin are two proteins that are found at the junction between two neurons and mutations in these proteins are associated with autism in humans. A common trait among all patients who are diagnosed with autism is that they are unable to integrate multiple sensory inputs and also have difficulty with social interactions. C. elegans mutants carrying the human disease-associated gene are also unable to integrate multiple sensory inputs and will not join social aggregates. That means that some aspects of this condition are conserved at the molecular level. I’m not saying that we have autism in C. elegans, as autism is a very complex disorder with lots of different factors, but some of the behaviors seem to be conserved. This result enables us to use the simple C. elegans model to find drugs or gene pathways that might help in alleviating the condition.

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