Ms. Anamika Sharma’s interview with Bio Patrika hosting “Vigyan Patrika”, a series of author interviews. Ms. Sharma is a PhD student in the lab of Prof. Gaiti Hasan at National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore. Anamika published a paper entitled “Modulation of flight and feeding behaviours requires presynaptic IP3Rs in dopaminergic neurons” as a first author in eLife journal (2020).
How would you explain your paper’s key results to the non-scientific community?
Our brain cells (neurons) need an adequate amount of calcium ions to function efficiently. Calcium ions can activate a neuron, which then communicates with other partner neurons and execute the final behaviour like walking, running or moving a finger. To function precisely, neurons have hence developed different ways to bring in and throw out calcium to maintain the required concentration. One of the proteins that help in this process is IP3R. IP3R is a calcium channel which is present on the membrane of a compartment of cell called Endoplasmic reticulum (ER). ER stores 1000 times more amount of calcium than any other place in the cell. On receiving appropriate signals, IP3R releases adequate amounts of calcium from ER whenever required. This calcium efflux through IP3R is very important as mutations in IP3R have been reported to affect human neuronal function and cause motor coordination defects like Spinocerebellar Ataxia (SCA) 15 and SCA 29, but how IP3R leads to neuronal dysfunction is not known.
It has been reported earlier that if of the same protein (IP3R) function in fruit flies (Drosophila) is compromised, it causes flight motor deficits. So, we used fruit fly to study its effects on neurons and then downstream behaviour. We made a non-functional version of IP3R, which does not release calcium from ER. After confirming its efficiency, we checked its effects on Drosophila neurons. We found that it reduces flight duration by affecting a particular set of neurons which produce dopamine. We further found that the expression of non-functional IP3R protein changed the essential properties of these flight regulating neurons, resulting in reduced output and less dopamine secretion. The neuronal output must communicate with other neurons and then coordinate the action of different neurons to execute the final behavioural task. Hence lesser dopamine release affected the functional output of downstream neurons and caused shorter flight bouts. We further found that the identified neurons are required for flight and food-seeking behaviour in hungry flies, which get affected when non-functional IP3R was expressed.
So results from our paper conclude that IP3R regulates adequate calcium concentration inside the neuron, which is required to maintain important properties of neurons and their output. If IP3R function gets compromised, it affects behaviours regulated by those neurons like it affects motivation to find food and flight to hover around in search of it, in the case of Drosophila.
“[…] study implies that dependent or linked behaviours can be co-regulated by similar neuronal circuits like same neuron controlling flight and food seeking.”
What are the possible consequences of these findings for your research area?
IP3R has been held responsible for motor coordination defects like SCA15 and SCA 29, but downstream mechanisms are still unknown. Our study proposes a possible mechanism to the disease in which malfunctioned IP3R changes cellular properties and then the output of neurons thereby affecting downstream motor behaviour. But it needs to be checked in human brain cultures derived from patients’ cells.
Also, scientists have been trying to understand the computation of complex behaviours in the brain. One of which is insect flight. Our study implies that dependent or linked behaviours can be co-regulated by similar neuronal circuits like the same neuron controlling flight and food-seeking.
What was the exciting moment (eureka moment) during your research?
I think the most exciting moments were when we found lesser dopamine release in our interested neurons and the involvement of the same flight neurons in food search behaviour. These two results gave us further insights as to how IP3R in a pair of neurons can be affecting a very broad behaviour like flight in an insect.
What do you hope to do next?
As I mentioned earlier, IP3R regulates calcium release from calcium store in the cell ER. This calcium is further taken up by other compartments of cells like mitochondria and lysosomes for their proper function. Mitochondria need calcium for various metabolic processes and to produce energy in the form of ATP. We are now trying to understand the possible roles of calcium release from IP3R in regulating mitochondrial functions in neurons.
Where do you seek scientific inspiration?
Every living organism can be narrowed down to a single functional entity, which is called a cell. Though microscopic, multiple dependent yet independent signalling cascades operate inside it. These cascades further consist of thousands of proteins operating at the right place of a cell at the right time in the right amounts. Complicated yet intricate and organised cellular machinery, which works 24X7 without fail, always mesmerises me and curiosity to know more about it, has always been my scientific inspiration. The motivation to follow my scientific curiosity comes from my parents. They don’t have a scientific background but still listen to all my experiments and make sure that failures don’t discourage me.
How do you intend to help Indian science improve?
I currently I talk to my juniors and help them prepare for various exams to pursue their scientific career. While talking to many students, I realised, talent exists everywhere, but lack proper guidance and educational support to inspire that talent in India. In the future, I would like to teach at different levels and talk to young minds about the importance of science and help them in pursuing their passion for science. I would also like to work at the interface of basic and applied science, where I could help multiple scientific labs working segregately in universities, industries and hospitals to come together and help each other grow.
Sharma A, Hasan G. Modulation of flight and feeding behaviours requires presynaptic IP3Rs in dopaminergic neurons. eLife 2020;9:e62297.
Learn more about Prof. Gaiti Hasan’s lab research interests here https://www.ncbs.res.in/faculty/gaiti