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Lights, Camera, Brain!

Sudhi Oberoi

Karl Deisseroth at the JN Tata Auditorium in IISc
Karl Deisseroth at the JN Tata Auditorium in IISc   (Photo: Cell Press-TNQ)

On 18th January 2016, the JN Tata Auditorium, Indian Institute of Science’s (IISc) biggest auditorium — both the main and ancillary halls — saw a packed audience. Professors, students and journalists flocked to reserve their seats in advance for the annual Cell-Press TNQ lecture: Illuminating the Brain” by Karl Deisseroth, D.H. Chen Professor of Bioengineering and of Psychiatry and Behavioral Sciences at Stanford University. He serves as an attending physician at Stanford Hospital and clinics and has been affiliated with Howard Hughes Medical Institute since 2009. Deisseroth is best known for developing techniques of optogenetics and CLARITY that have revolutionised the field of neuroscience.

Deisseroth says that his big moment of epiphany came during interactions with suffering psychiatric patients, when he realised how little is known about the brain circuits and connections underlying these debilitating disorders. Back in his lab he looked around for a method to investigate specific circuits of the brain while probing behaviour, only to realise that none existed. In his quest to tackle this problem, he stumbled upon bacteria and algae that contain special light-responsive proteins called opsins’ that convert light into electric charge across the cell’s membrane. He recognised that these proteins could be inserted in brain cells, or neurons, to switch them on or off. This realisation marked the beginning of the field he christened Optogenetics”, which he developed with his early students Feng Zhang and Edward Boyden (both now Professors at the Massachusetts Institute of Technology). As the name suggests optogenetics uses a combination of optics and genetics to make neurons behave like genetically encoded optical sensors — it enables manipulation of the neuronal activity with spatial and temporal precision. Optogenetics has been a water-shed moment in neuroscience providing, for the first time, the ability to not simply observe but disrupt and modify specific neural circuits and observe associated changes in behaviour. It is now being used extensively to address questions that could not be addressed earlier and fetched Deisseroth the prestigious 2015 Breakthrough Prize in Life Sciences.

Deisseroth quickly moved to his next big contribution to neuroscience. Imaging any biological tissue and especially the brain has proved to be very hard simply because the tissue contains lipids that are opaque, not allowing light to travel through. In order to visualise the brain, scientists earlier sectioned it into very thin slices and then re-aligned them: a process that was both imprecise and extremely painstaking. Deisseroth’s lab has recently developed a chemical process — with an apt acronym, CLARITY — which renders the brain transparent. In this method, neurons can be tagged specifically and then trapped in a web of hydrogel. All other light-scattering components of the brain are then treated with detergent and removed using small and constant electric charge (electrophoresis), leaving the field clear to image neurons.

True to his nickname, The Method Man”, this neuroscientist-psychiatrist-bioengineer believes that science is often driven by technologies rather concepts. Ajit Ray, a student at IISc who was at the talk said, It was an excellent talk. It provided great insight into how light can be used to illuminate brain structure and function.”

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