Work done in the lab of Rishikesh Narayanan at Cellular Neurophysiology Laboratory, Molecular Biophysics Unit, Indian Institute of Science.
About author
Harshith Nagaraj completed his Bachelor of Science (Research) and Master of Science from the Indian Institute of Science, Bangalore. A neuroscience enthusiast, he worked in the lab of Prof. Rishikesh Narayanan at MBU, IISc for his Bachelors’ as well as Masters’ theses, for which he was awarded the Institute Gold medal in Biology. He is currently a graduate student at McGill University where he studies the neural circuitry of spatial navigation and orientation. He is fascinated by all things related to neuroscience, and loves to discuss ideas about how the brain works. He is also an avid reader and a huge cricket fan and spends most of his time watching and analysing it when he’s not working !!
Interview
How would you explain your research outcomes to the non-scientific community?
The day-night cycle is an important factor regulating the physiology and behaviour of organisms on Earth. Animals synchronize to this environmental cycle through an internal “clock”, which in mammals is housed in a brain region called the suprachiasmatic nucleus (SCN). Neurons in the SCN change their properties (such as firing rate) across the time of day to encode the cycle. These transitions are caused by the changes in expression of a few key molecules called ion channels (a phenomenon termed ion-channel plasticity), which regulates the properties of these neurons.
In the presence of variability between neurons, a key question that remains unanswered is how these neurons maintain stability while multiple ion channels undergo concurrent changes across cycles.
To address this question, we generated a population of model day and night SCN neurons using a random search procedure. Analyses on these populations revealed that multiple combinations of ion-channel levels could yield neurons with similar properties, a phenomenon known as ‘ion-channel degeneracy’. Further, we observed that for neurons to transition from a day state to a night state, only a few combinations of changes in ion-channel levels are possible. This can be visualized as a structure called a ‘plasticity manifold’. If we represent all possible combinations of changes in ion-channel levels as a 3D space, a plasticity manifold would be a plane structure (like a sheet of paper), where only the changes that fall along the plane structure are possible.
Thus, we demonstrate that SCN neurons can maintain stability during transitions over the day-night cycle through a combination of the two phenomena described above: a) multiple ion-channel combinations can yield neurons with similar properties, and b) only a small number of combinations of changes in ion-channel levels are possible during these day-to-night transitions.
How do these findings contribute to your research area?
While extensive literature has focused on how behavioural changes might be regulated by manifolds at the level of neural networks (known as neural manifolds), the idea that a similar structure can be found even at the molecular level (i.e., plasticity manifolds) is still relatively recent. These may be crucial to be accounted for in other physiological scenarios and may play important roles in pathological conditions as well as in therapeutics.
“Plasticity manifolds and degeneracy govern circadian oscillations of neuronal intrinsic properties in the suprachiasmatic nucleus”
What was the exciting moment during your research?
Since not a lot of work has been done on the idea of ‘plasticity manifolds’, the most exciting moment was when we got the result confirming that there are indeed these structures present during day-to-night transitions. It was extremely interesting that there is a generalization of properties in biology across different scales (cellular scale to molecular scale in this case). Also, it was a really exciting day when we got our first model to work, as it was the first real result we had after a lot of work 😊!
What do you hope to do next?
I am currently a graduate student at McGill University, where I am studying the neural circuitry underlying spatial navigation. I hope to further our understanding of how the brain helps animals to orient themselves and navigate their environment effectively. In the long term, I hope to contribute to answering the biggest question in neuroscience: how does the brain control behaviour?
Where do you seek scientific inspiration from?
While my main motivator to take up neuroscience has been my mother, I draw inspiration from my mentor Rishi who helped lay a foundation for me in understanding the field, as well as the work of eminent neuroscientists such as Hodgkin-Huxley, Edward Tolman, Hubel and Wiesel whose work increased my fascination for neuroscience. I also draw inspiration from Indian scientists who come from similar backgrounds and continue to contribute to the growth of science, in general, and Indian science, in particular.
How do you intend to help Indian science improve?
In a country like India which has immense potential for growth in science, I hope to someday be able to open my lab in India to study neuroscience and increase opportunities for Indian students who share my fascination with the brain to engage in the same. In the words of the IPL trophy “Where talent meets opportunity”, I hope to someday be part of the “opportunity” side of things for the “talent” that exists in India 😊!
Reference
Nagaraj, H. and Narayanan, R., 2023. Plasticity manifolds and degeneracy govern circadian oscillations of neuronal intrinsic properties in the suprachiasmatic nucleus. Iscience, 26(4) : https://www.sciencedirect.com/science/article/pii/S2589004223005801
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